DAA-based therapies effective for HCV patients with chronic kidney disease
Direct-acting antiviral (DAA)-based therapies are effective and well-tolerated for HCV patients with stage four to five chronic kidney disease, a meta-analysis of published studies shows.
Reviewers at the Second Hospital of Shandong University in China found 11 studies involving a total of 264 patients. The pooled SVR12 rate was 93.2% for the total population, 89.4% for sofosbuvir-based therapies, and 94.7% for non-sofosbuvir-based therapies. For HCV genotype 1 patients, the pooled SVR12 rate was 93.1%.
The pooled incidence of serious adverse events was 12.1%, and the pooled discontinuation rate because of adverse events or serious adverse events was 2.2%.
Efficacy and safety of DAA-based antiviral therapies for HCV patients with stage 4-5 chronic kidney disease: a meta-analysis. Li T, Qu Y, Guo Y et al. Liver Int. 2016 Dec 10 [Epub ahead of print]
Haemophilia does not affect liver transplant outcomes in HCV patients
A large observational study in the USA confirmed haemophilia per se does not have a specific influence on transplant outcomes in HCV patients, but that HIV infection increases the risk of mortality in both haemophilic (H) and non-haemophilic (NH) patients.
Researchers identified 2,502 HCV-positive liver transplant candidates from eight US university-based transplant centres between 2004 and 2010, including 144 HIV-positive and 2,358 HIV-negative; 36 H and 2,466 NH; 1,213 transplanted and 1,289 not transplanted patients.
In univariate analysis, 90-day pre-transplant mortality was associated with higher baseline MELD (hazard ratio 1.15), lower baseline platelet count (hazard ratio 1.11 per 25k/µL), and having HIV/HCV-positive haemophilia.
In multivariate analysis, pre-transplant mortality was associated with higher MELD and was significantly greater in HIV-positive than HIV- groups, but did not differ between HIV-positive H and NH (hazard ratio 1.7). Among HIV/HCV-positive, post-transplant mortality was similar between H and NH, despite lower CD4 in H.
Haemophilia liver transplantation observational study (HOTS). Ragni MV, Humar A, Stock PG et al. Liver Transpl. 2016 Dec 9 [Epub ahead of print]
Mechanisms of IFN-α-induced depression in HCV are unclear
A significant number of HCV patients develop a major depressive episode (MDE) during interferon-alpha (IFN-α) based immunotherapy, and several mechanisms may be involved.
Authors of a new literature review found eight unique references which met their inclusion criteria, and which involved 826 people with HCV (37.3% females). The overall MDE incidence rate was 34.8%, with follow-up ranging between four and 48 weeks. The methodological quality varied across selected studies. It was found that Interleukin-6, salivary cortisol, arachidonic acid/eicosapentaenoicacid plus ocosahexaenoic acid ratio, and genetic polymorphisms may present variations which are linked to a predisposition to INF-α-induced depression.
However, a meta-analysis could not be performed because of the diverse biological mechanisms investigated and the lack of replicated evidence. The reviewers, therefore, concluded the mechanisms involved in IFN-α-induced depression in humans remained unclear.
Biological mechanisms of depression following treatment with interferon for chronic hepatitis C: a critical systematic review. Machado MO, Oriolo G, Bortolato B et al. J Affect Disord. 2016 Nov 27; 209:235-245 [Epub ahead of print]
Some NASH patients have recurring fibrosis shortly after transplant
Some patients with non-alcoholic steatohepatitis (NASH) show recurrence of fibrosis as early as six to 12 months following their transplant.
This emerged in a study at the Medical University of Vienna which compared the recurrence of liver fibrosis in 15 patients transplanted for NASH with 12 to cryptogenic cirrhosis (CC) patients after orthotopic liver transplantation (OLT) between 2004 and 2015.
The case load for OLT because of NASH was constantly increasing (two in 2004-2007 compared with nine in 2012-2015) whilst decreasing for CC (six in 2004-2007 compared with two in 2012-2015). Patient characteristics at OLT were similar, except for an older age and a higher BMI in the NASH patients.
Although post-OLT plasma lipid levels and the incidence of de-novo hypertension, diabetes, and hyperlipidemia were similar between groups, the post-transplant NAFLD fibrosis score (NFS) re-increased in the NASH group but not in the CC group (-0.1317 versus -1.3645 at 12 months post-OLT.
The post-transplant course of patients undergoing liver transplantation for nonalcoholic steatohepatitis versus cryptogenic cirrhosis: a retrospective case-control study. Unger LW, Herac M, Staufer K et al. Eur J Gastroenterol Hepatol. 2016 Dec 2 [Epub ahead of print]
New DAAs “a very important advance” for HCV in haemodialysis patients
A new study has concluded that the new direct-acting antivirals (DAAs) are highly effective with minimal adverse effects for the treatment of HCV in haemodialysis, and are a very important advance in HCV management.
In this retrospective study, HCV antibodies were analysed in 465 patients at two Madrid hospitals. Positive antibodies were found in 54, and, among these, 29 with genotypes 1 and 4 were treated with different DAA regimens, including combinations of paritaprevir/ritonavir, ombitasvir, dasabuvir, sofosbuvir, simeprevir, daclatasvir and ledipasvir, with/without ribavirin. The most important aetiology of chronic kidney disease involved glomerular abnormalities.
In all cases, a sustained viral response was achieved after 24 weeks, regardless of DAA regimen received. Adverse effects were not relevant and no case required stopping treatment. In 15 cases, ribavirin was combined with the DAA. In these cases, the most significant adverse effect was an anaemic tendency, which was reflected in the increase of the dose of erythropoietin stimulating agents, although none required transfusions.
Effectiveness of direct-acting antivirals in Hepatitis C virus infection in haemodialysis patients. Abad S, Vega A, Rincón D et al. Nefrologia. 2016 Nov 30 [Epub ahead of print]
Similar long-term efficacy between tenofovir and entecavir in HBV related cirrhosis
Although tenofovir (TDF) was more effective at three months, there was no significant difference between TDF and entecavir (ETV) in the long-term treatment of HBV related liver cirrhosis, a new meta-analysis of studies found.
A literature search, conducted by reviewers from Beijing You'an Hospital, found significant difference of ALT norm level at three months (RR 1.43) and six months (RR 0.89), and significant difference of undetectable HBV-DNA only at three months follow-up period (RR 1.59) between TDF and ETV, but no significant difference in the long-term period. There was a significant difference between TDF and ETV in eGFR level (RR 1.601) and hypophosphatemia incidence (RR 4.008).
The efficacy and safety comparison between tenofovir and entecavir in treatment of chronic hepatitis B and HBV related cirrhosis: a systematic review and meta-analysis. Han Y, Zeng A, Liao H et al. Int Immunopharmacol. 2016 Dec 1;42: 168-175 [Epub ahead of print]
Women with HBV lose anti-cirrhosis advantage as they get older
A new study of HBV patients shows that the protective effect against cirrhosis of being female is gradually lost with increasing age.
This multicentre study from China investigated the interaction of female gender and older age on the development of cirrhosis in patients recorded in the China Registry of HBV. A total of 17,809 chronic HBV patients were studied.
The prevalence of cirrhosis in the females increased faster than that in the males over 50 years old. Multivariate analysis showed that the increase of adjusted odds ratios for developing cirrhosis in females started to accelerate after 50 years of age: 11.19 in women versus 14.75 in men aged 50 to 59; 21.67 versus 24.4 at ages 60 to 69; and 18.78 versus 12.09 in those aged over 70.
The study authors suggest that disease progression should be monitored more closely in elderly women with chronic HBV.
Female gender lost protective effect against disease progression in elderly patients with chronic hepatitis B. You H, Kong Y, Hou J et al. Sci Rep. 2016 Nov 28;6: 37498
New studies show simeprevir plus sofosbuvir safe and effective in HCV
Two otherwise unrelated studies have testified to the efficacy and safety of the combination of simeprevir and sofosbuvir in patients with HCV.
In the US-based GALAXY study, the combination, with or without ribavirin, was efficacious and well tolerated in patients with recurrent HCV genotype 1 post-orthotopic liver transplant (1).
Thirty-three such patients without cirrhosis were randomised into three arms: Arm 1, received simeprevir+sofosbuvir+ribavirin for 12 weeks; Arm 2, received simeprevir+sofosbuvir for 12 weeks; Arm 3 received simeprevir+sofosbuvir for 24 weeks; 13 additional subjects (two with cirrhosis, 11 without cirrhosis) entered Arm 3.
Among the randomised subjects, SVR12 was achieved by 81.8% in Arm 1, 100% in Arm 2, and 93.9% in Arm 3; two subjects did not achieve SVR12: one viral relapse
(follow-up Week 4; Arm 1) and one missing follow-up Week 12 data. Five subjects had a serious adverse event, considered unrelated to treatment per investigator.
In Spain’s PLUTO study, the combination of simeprevir plus sofosbuvir for 12 weeks resulted in SVR12 rates of 100% in treatment-naïve and -experienced patients with HCV genotype 4 with or without compensated cirrhosis, and was well tolerated (2).
Forty patients received the combination for 12 weeks. Seven of the patients had compensated cirrhosis. All achieved SVR12. Adverse events, all Grade 1 or 2, were reported in 20 patients. No serious adverse events were reported and no patients discontinued study treatment. Grade 3 treatment-emergent laboratory abnormalities occurred in two patients.
Efficacy and safety of simeprevir and sofosbuvir with and without ribavirin in subjects with recurrent genotype 1 hepatitis C post-orthotopic liver transplant: the randomized GALAXY study. O'Leary JG, Fontana RJ, Brown K et al. Transpl Int. 2016 Nov 29 [Epub ahead of print]
Simeprevir in combination with sofosbuvir in treatment-naïve and -experienced patients with hepatitis C virus genotype 4 infection: a Phase III, open-label, single-arm study (PLUTO). Buti M, Calleja JL, Lens S et al. Aliment Pharmacol Ther. 2016 Nov 29 [Epub ahead of print]
Hepatocellular carcinoma increase rate slows in USA
The overall rate of increase in hepatocellular carcinoma (HCC) slowed between 2010 and 2012, found a nationwide US study. However, it did increase in some sub-groups such as men aged 55 to 64, and whites/Caucasians.
Researchers at Baylor College of Medicine in Texas analysed data from the US Cancer Statistics registry, which covers 97% of the population of all 50 states.
They found that the HCC incidence increased from 4.4/100,000 in 2000 to 6.7/100,000 in 2012, increasing by 4.5% annually between 2000 and 2009, but only by 0.7% annually between 2010 and 2012.
The average annual percentage change (AAPC) between 2000 and 2012 was higher in men (increase of 3.7%) than women (increase of 2.7%), and highest in 55 to 59-year-olds (AAPC 8.9%) and 60 to 64-year-olds (AAPC 6.4%).
By 2012, rates in Hispanics surpassed those in Asians, and rates in Texas surpassed those in Hawaii (9.71/100,000 vs 9.68/100,000). Geographic variation within individual race and ethnic groups was observed, but rates were highest in all major race and ethnic groups in Texas.
Incidence of hepatocellular carcinoma in all 50 United States, from 2000 through
2012. White DL, Thrift AP, Kanwal F et al. Gastroenterology. 2016 Nov 23 [Epub ahead of print]
Three anti-HCV regimens “highly effective” in achieving SVR
A comparison of three different anti-HCV regimens concluded that all of them appeared highly effective in achieving sustained virologic response (SVR).
A study at the University of Southern California compared the SVR rates achieved 12 weeks post-treatment in 11,464 patients treated with three such agents by the Veterans Health Administration.
Without controlling for other risk factors, a SVR at least 12 weeks post treatment was achieved in 92% of ledipasvir/ sofosbuvir, 86% of ombitasvir/paritaprevir/ritonavir/dasabuvir, and 83% of simeprevir/sofosbuvir patients.
After adjusting for patient characteristics, simeprevir/sofosbuvir (93.3%) and ledipasvir/sofosbuvir (96.2%) patients were statistically more likely than ombitasvir/paritaprevir/ritonavir/dasabuvir (91.8%) patients to demonstrate a SVR.
HIV, HBV, diabetes, obesity, previous treatment history and augmentation therapy using ribavirin did not impact the SVR rates. Sustained SVR rates were lower for patients under age 65, with cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, indications of fibrosis or a non-genotype 1 infection. Women and Caucasian patients were more likely to achieve a SVR.
Comparative treatment effectiveness of direct acting antiviral regimens for hepatitis C: data from the Veterans Administration. Fox DS, McGinnis JJ, Tonnu-Mihara I et al. J Gastroenterol Hepatol. 2016 Nov 21 [Epub ahead of print]
Hepatitis increases risk of uveitis
A new study finds that people with viral hepatitis are at an increased risk of uveitis, particularly those with both HBV and HCV.
Researchers at China Medical University, Taichung, used data from the Taiwan National Health Insurance system to identify 17,389 patients newly diagnosed with viral hepatitis between 2000 and 2011 and matched these with 34,778 controls.
The risk of uveitis in the hepatitis cohort was 1.30-fold. Those with HBV and HCV coinfection had the highest risk (hazard ratio = 2.88), followed by HCV only infection (hazard ratio 1.75). Patients with cirrhosis had a higher risk in the multivariable model but did not attach statistic difference.
Relationship between uveitis, different types of viral hepatitis, and liver cirrhosis: a 12-year nationwide population-based cohort study. Tien PT, Lin CJ, Tsai YY et al. Retina. 2016 Dec;36(12):2391-2398
Statins reduce HCC risk in people with type 2 diabetes
The use of statins by people with type 2 diabetes may help them avoid developing hepatocellular carcinoma (HCC), new evidence suggests.
Researchers at Yonsei University College of Medicine in Seoul, carried out a Korean nationwide population-based study involving 47,738 patients with type 2 diabetes.
After at least a five-year HCC-free period there were 229 incident HCC cases and 1,145 matched controls. Of these 229 incident HCC cases, 27 were statin users, whereas 378 were statin users among 1,145 controls.
Statin use was associated with a reduced risk of HCC development (adjusted odds ratio 0.36) after adjustment for chronic viral hepatitis, liver cirrhosis, alcoholic liver disease, previous cancer, aspirin use, insulin use, sulfonylurea use, metformin use, thiazolidinedione use, history of chronic obstructive pulmonary disease, Charlson comorbidity score, household income level, and residential area.
The risk reduction was accentuated with an increase of cumulative defined daily doses (cDDD) compared with non-users (adjusted odds ratios 0.53, 0.36, 0.32, and 0.26 in ≤60, 60-180, 181-365, and >365cDDD, respectively).
The risk reduction was apparent in the presence of liver disease (adjusted odds ratio 0.27), including heterogeneous groups of clinical diagnosis of liver disease, but not significant in the absence of liver disease (adjusted odds ratio 0.64).
Effect of statin on hepatocellular carcinoma in patients with type 2 diabetes: A
nationwide nested case-control study. Kim G, Jang SY, Han E et al. Int J Cancer. 2016 Nov 7 [Epub ahead of print]
Liver cancer risk reduced in patients cured of HCV
A large study found that the risk of hepatocellular carcinoma was reduced by 80% in people cured of HCV compared to those who were not cured.
This was a study of the entire population of people treated for HCV in British Columbia province, Canada, between 1990 and 2013. The study identified 8147 people treated with interferon-based regimens, 57% of whom were cured. Treated individuals were followed for a median of 5.6 years.
The liver cancer incidence was highest among those with cirrhosis who did not achieve a SVR (21 cases per 1000 patient-years of follow-up). In comparison, the liver cancer incidence was 6.4 per 1000 patient-years in those with cirrhosis who achieved SVR, 7.2 in those without cirrhosis who did not achieve SVR12 and 1.1 per 1000 patient-years in those without cirrhosis who achieved SVR12.
In a multivariable analysis liver cancer was associated with cirrhosis, age over 50 years, genotype three infection versus genotype one, alcohol consumption and being male in those who were not cured. In those who were cured of hepatitis C, only cirrhosis, age over 50 and being male were associated with an increased risk of liver cancer.
The researchers concluded that although curing HCV greatly reduces the risk of developing liver cancer, it does not eliminate the risk entirely. Older people and those with cirrhosis are at higher risk than others, underlining the importance of early diagnosis and treatment.
The impact of sustained virological response to HCV infection on long term risk of hepatocellular carcinoma: the BC Hepatitis Testers Cohort. Janjua NZ et al. The 67th Meeting of the American Association for the Study of Liver Diseases, Boston 2016. Abstract 175
Sofosbuvir plus velpatasvir “best options” for HCV G3
An analysis of published studies on direct acting antivirals (DAAs) found that regimens containing sofosbuvir and velpatasvir were the best option for patients with HCV genotype three (G3).
The analysis indicated that ribavirin significantly increased rates of SVR and should be considered if tolerated.
Researchers at Radboud University Medical Centre in the Netherlands performed a Bayesian network meta-analysis using a random effects model to indirectly compare DAA regimens in HCV G3 patients with and without cirrhosis. They found 27 appropriate studies involving 3,415 patients.
Among patients without cirrhosis, the greatest rates of SVR were estimated for those receiving sofosbuvir + velpatasvir with ribavirin (99%) and without ribavirin (97%), for sofosbuvir + daclatasvir + ribavirin (96%), and for sofosbuvir + peginterferon + ribavirin (95%), all for 12 weeks.
Among patients with cirrhosis, the highest rates of SVR were estimated for those receiving sofosbuvir + velpatasvir for 24 weeks (96%), for sofosbuvir + daclatasvir + ribavirin for 24 weeks (94%), and for sofosbuvir + velpatasvir + ribavirin for 12 weeks (94%).
Ribavirin increases efficacy in patients with and without cirrhosis (odds ratios 2.6 and 4.5).
Identification of the best direct-acting antiviral regimen for patients with hepatitis C virus genotype 3 infection: a systematic review and network meta-analysis. Berden FA, Aaldering BR, Groenewoud H et al. Clin Gastroenterol Hepatol. 2016 Nov 10 [Epub ahead of print]
Psychosocial distress worsens in families during HCV treatment
A new study suggests young people being treated for HCV and their families experience increasing psychosocial distress.
During the study period, 10 children with HCV and their families began treatment at New York’s Icahn School of Medicine. Each family was given a battery assessing patient quality of life, caregiver distress related to their child's illness and overall family functioning.
At baseline, the patients displayed a poorer quality of life than population norms, caregiver distress was elevated and family functioning was also in the "stressed" range. After treatment, all parameters worsened.
The researchers suggest caregivers may benefit from additional support given the implications of HCV and grueling nature of its treatment. Broadly, the impact of continuous intensive treatments on families perhaps should be monitored.
Children with hepatitis C: the impact of disease and treatment on patients, caregivers and families. Annunziato RA, Lee SG, Galici E et al. J Pediatr Nurs. 2016 Nov 8 [Epub ahead of print]
Large gaps in HCV and HBV testing in Europe
There are large gaps in the quality and diversity of HCV and HBV testing in many European countries, a literature review suggests.
Reviewers from the University of Copenhagen found 136 English-language studies from 24 European countries published between January 2007 and June 2013. Most of the studies took place in six countries: France, Germany, Italy, the Netherlands and the United Kingdom.
Thirty-seven studies addressed HBV, 46 addressed HCV, and 53 addressed both diseases. The largest categories of study populations were people who use drugs (18%) and health care patient populations (17%). Far fewer studies focused on migrants, prison inmates, or men who have sex with men. The reviewers concluded that more research is needed throughout Europe to guide efforts to provide testing to certain key populations.
Are the testing needs of key European populations affected by hepatitis B and
hepatitis C being addressed? A scoping review of testing studies in Europe. Lazarus JV, Sperle I, Spina A et al. Croat Med J. 2016 Oct 31;57(5):442-456
Coffee may reduce risk of NAFLD
People who drink coffee are less likely to develop nonalcoholic fatty liver disease (NAFLD), a new literature review suggests. And people with NAFLD who drink coffee regularly are less likely to develop liver fibrosis.
Reviewers from the Bassett Medical Centre, New York, carried out two meta-analyses. The first included observational studies comparing the risk of NAFLD in patients who did and did not drink coffee. The second analysis included studies comparing the risk of liver fibrosis between NAFLD patients who did and did not drink coffee.
Out of 355 articles, five studies fulfilled the eligibility criteria and were included in the analysis. The risk of NAFLD in patients who drank coffee was significantly lower than that in patients who did not (pooled risk ratio 0.71). There was also a significantly decreased risk of liver fibrosis among NAFLD patients who drank coffee compared with those who did not, with a pooled risk ratio of 0.70.
However, say the reviewers, it should be noted that the definition of regular coffee consumption varied between studies, which is the main limitation of this meta-analysis. They add that whether consumption of coffee could be considered a preventative measure against NAFLD needs further investigation.
Coffee consumption and risk of nonalcoholic fatty liver disease: a systematic review and meta-analysis. Wijarnpreecha K, Thongprayoon C, Ungprasert P. Eur J Gastroenterol Hepatol. 2016 Nov 7. [Epub ahead of print]
Women who don’t drink have improved spontaneous HCV clearance
Abstaining from alcohol increases the likelihood of spontaneous HCV clearance among women, a new international study suggests.
The study involved pooled data from observational studies in Australia, the Netherlands and the USA and included 411 high risk persons (or 560.7 person-years of observation) with documented acute HCV infection and data regarding alcohol use. Their median age was 28.5 years, 30.4% were women, 87.2% were white, and 71.8% reported alcohol use at or after incident infection.
There were 89 (21.6%) cases of spontaneous clearance, 39 (31.2%) among women and 50 (17.5%) in men. Overall, spontaneous clearance occurred less frequently among participants who drank alcohol compared to those who did not drink (18.9% versus 28.5%). After adjustment for other covariates, alcohol was significantly and independently associated with lower relative hazards for spontaneous clearance of HCV in women (adjusted hazard ratio 0.35) but not in men (adjusted hazard ratio 0.63).
The effects of alcohol on spontaneous clearance of acute hepatitis C virus infection in females versus males. Tsui JI, Mirzazadeh A, Hahn JA et al. Drug Alcohol Depend. 2016 Oct 26; 169:156-162 [Epub ahead of print]
Despite HBV vaccination programmes, vertical transmission still occurs at birth
Even in countries with a low HBV prevalence and a national vaccination programme, vertical HBV transmission can still occur amongst children born to HBV-infected mothers, new research suggests.
In Denmark, pregnant women have been screened for HBV since 2005, and children born to HBV-infected mothers offered HBV immunoglobulin at birth, vaccination against HBV at birth and after one, two and 12 months.
Through the Danish Database for HBV, researchers identified 589 HBV-infected women who had given birth to 686 children, of whom 370 children were born to 322 women referred to hospital. A total of 132 children born to 109 mothers, were included in the study; 128 children had blood samples tested for HBsAg, anti-HBc (total), anti-HBs and HBV-DNA and four children had saliva samples tested for anti-HBc.
There was a vertical HBV transmission of 2.3%, a high proportion of HBsAg-negative children with low levels of anti-HBs (18.4%) and a high proportion (15.2%) with resolved HBV infection. No maternal risk factor was statistically significantly associated with HBV vertical transmission.
Vertical transmission of hepatitis B virus during pregnancy and delivery in Denmark. Weis N, Cowan S, Hallager S et al. Scand J Gastroenterol. 2016 Oct 31:1-7 [Epub ahead of print]
NAFLD patients with advanced liver fibrosis have low vitamin D
New evidence shows that low vitamin D is associated with advanced liver fibrosis in nonalcoholic fatty liver disease (NAFLD) patients
In a study at Anhui Medical University in China, 219 NAFLD patients and 166 matched healthy controls had their serum 25(OH)D, serum interleukin-8, and transforming growth factor-β1 measured.
Serum 25(OH)D was only marginally decreased in the NAFLD patients. However, serum 25(OH)D was markedly reduced in those NAFLD patients with advanced liver fibrosis compared to those with indeterminate liver fibrosis and no advanced fibrosis.
Logistic regression analysis showed that there was an inverse association between serum 25(OH)D and the severity of liver fibrosis in the NAFLD patients.
Further analysis showed that serum interleukin-8 was elevated in the NAFLD patients, the highest interleukin-8 being in those with advanced fibrosis. An inverse correlation between serum 25(OH)D and interleukin-8 was seen in NAFLD patients with and without liver fibrosis.
Although serum transforming growth factor-β1 was slightly elevated in NAFLD patients, serum transforming growth factor-β1 was reduced in those with advanced fibrosis. Unexpectedly, a positive correlation between serum 25(OH)D and transforming growth factor-β1 was seen in NAFLD patients with advanced fibrosis.
The researchers suggest that interleukin-8 may be an important mediator for hepatic fibrosis in NAFLD patients with low vitamin D status.
Low vitamin D status is associated with advanced liver fibrosis in patients with nonalcoholic fatty liver disease. Yang BB, Chen YH, Zhang C et al. Endocrine. 2016 Oct 31. [Epub ahead of print]
People with HCV are at risk of chronic kidney disease
Findings from a new literature review show that people with HCV are at a significant risk of experiencing chronic kidney disease (CKD).
The reviewers, from Binzhou Medical University in China, found 12 appropriate longitudinal studies involving 1,972,044 subjects, and 15 cross-sectional studies involving 937,607 people.
Overall effect estimate was remarkably significant in the longitudinal studies (hazard ratio 1.45) in contrast to that in the cross-sectional studies (odds ratio 1.25), with obvious heterogeneity.
HCV infection was also associated with a 1.54-fold increased risk of
having prevalent proteinuria. In longitudinal studies with estimated glomerular
filtration rate (eGFR) < 60, < 30 and < 15 ml/min/1.73m2, the corresponding hazard ratios were 1.39, 1.79 and 2.30, respectively.
Further grouping of the longitudinal studies by median follow-up time at five years revealed that the effect estimate was reinforced in long-term studies (hazard ratio 1.86) relative to that in short-term studies (1.21).
The reviewers summarized that their findings demonstrate the significant risk of experiencing incident CKD after HCV infection, with the lower eGFR and longer HCV exposure time entailing a greater risk.
A systematic review and meta-analysis: Does hepatitis C virus infection predispose to the development of chronic kidney disease? Li M, Wang P, Yang C et al. Oncotarget. 2016 Oct 25 [Epub ahead of print]
Evidence shows value of treating all stages of chronic HCV
Available evidence suggests that HCV treatment with the new direct-acting antivirals (DAAs) should not be limited to patients with advanced liver disease.
A new literature review has provided an overview of the clinical and economic benefits of achieving SVR and to better understand the full value of chronic HCV treatment in all stages of liver disease. Overall, the review identified 354 studies involving more than 500,000 chronic HCV patients worldwide.
Evidence from 38 studies, involving 73,861 patients, showed a significant mortality benefit of achieving SVR in patients with all stages of fibrosis. Long-term studies with follow-ups of five to 12 years suggested that, particularly among non-cirrhotic patients, there was a significant decrease in mortality in SVR versus non-SVR groups.
Ninety-nine studies conducted in 235,891 chronic HCV patients in all stages of fibrosis showed that SVR reduced liver-related mortality, the incidence of hepatocellular carcinoma, and decompensation.
A total of 233 studies showed that chronic HCV infection was associated with several serious extrahepatic manifestations, some of which can have high mortality. Evidence from four modeling studies showed that delaying treatment to chronic HCV patient populations could significantly increase mortality, morbidity, and medical costs.
The review concludes that there is a robust body of evidence demonstrating diverse sources of value from achieving SVR in all stages of liver disease. While access to treatment is generally limited to late-stage patients, less restrictive treatment strategies that target HCV eradication have the potential to abate the burdens of mortality, liver morbidity and extrahepatic manifestations, and the associated healthcare costs.
Value of treating all stages of chronic hepatitis C: a comprehensive review of clinical and economic evidence. Nuño Solinís R, Arratibel Ugarte P, Rojo A et al. Infect Dis Ther. 2016 Oct 25. [Epub ahead of print]
Old age not a barrier to major hepatectomy for colorectal liver metastases
Well-selected elderly patients with colorectal liver metastases should be considered for major hepatectomy, followed by adjuvant chemotherapy.
This was the recommendation of researchers from St James University, Leeds, and Auckland City Hospital, who reviewed 727 patients who underwent major hepatectomy for colorectal liver metastases between 1996 and 2011. Of these, 105 were aged ≥75.
Morbidity was greater in the ≥75 group (25% versus 34%) but there was no difference in mortality. There was no difference in disease-free survival (DFS) between the two groups at five years (16.8 months versus 18.9 months). Overall survival (OS) was longer in the <75 group (38.6 months versus 32.0 months). DFS was better in groups
receiving adjuvant chemotherapy than those who did not (<75, 24.2 months versus 12.2 months, and ≥75, 24 months versus 12.1 months).
OS in the ≥75 group was improved in the group receiving adjuvant chemotherapy compared to those who did not (41.1 months versus 16.6 months). Age ≥75 was not an independent risk factor for reduced DFS on multivariate analysis.
The impact of advancing age on recurrence and survival following major hepatectomy for colorectal liver metastases. Bell R, Pandanaboyana S, Nisar S et al. J Gastrointest Surg. 2016 Oct 21. [Epub ahead of print]
Less HDV progression with IFNα-based treatment
In patients with HDV, pegylated interferon alfa (IFNα)-based therapy was independently associated with a lower likelihood for clinical disease progression than nucleos(t)ide analogues (NA) only.
In a study at Hannover Medical School, 136 anti-HDV-positive patients were followed for a mean time of 5.2 years. Liver cirrhosis was already present in 62 patients at first presentation. Twenty-nine percent did not receive any antiviral treatment, 38% were treated with IFNα-based therapies and 33% received NAs only.
Clinical endpoints defined as hepatic decompensation (ascites, encephalopathy, variceal bleeding), hepatocellular carcinoma, liver transplantation and liver-related death developed in 55 patients.
The patients who received IFNα-based therapies developed clinical endpoints less frequently than those treated with NAs (hazard ratio 0.02) or untreated patients (hazard ratio 2.2), which was significant in both chi-square and Kaplan-Meier analysis. In addition, considering various clinical and virological parameters, IFNα therapy was independently associated with a more benign clinical long-term outcome in multivariate logistic regression analysis (odds ratio 0.25). Loss of HDV RNA during follow-up was more frequent in the IFNα-treated patients and strongly linked with a lower likelihood to
experience liver-related complications.
Antiviral treatment and liver-related complications in hepatitis delta. Wranke A, Calle Serrano B, Heidrich B et al. Hepatology. 2016 Oct 22 [Epub ahead of print]
Sofosbuvir/ribavirin “effective and tolerable” in elderly HCV G2 patients
The combination of sofosbuvir plus ribavirin (RBV) is effective and tolerable in elderly HCV genotype two (G2) patients, a new Japanese study reported.
Thirty-seven HCV G2 patients aged 75 or older ,and 19 aged under 75 were treated with sofosbuvir and weight-based dose of RBV. The older group included more women, and had more history of hepatocellular carcinoma, lower serum albumin (ALB) level, lower haemoglobin (Hb) concentration, lower estimated glomerular filtration rate (eGFR), and a higher fibrosis-4 index.
Forty-one patients were evaluated for SVR at 12 weeks after the end of therapy (SVR12); of them, all but one completed the treatment scheduled for 12 weeks. The older group had a lower SVR12 rate than the younger group (81.3% versus 96.0%, respectively).
Although the Hb concentration and eGFR were significantly lower in the older group throughout the clinical course, all patients in this group completed the 12-week treatment with a gradual increase of serum ALB level.
The researchers noted that although the drug combination is tolerable and beneficial in patients aged over 75, intensive management of anaemia by dose reduction of RBV is necessary, which could lead to a low SVR12 rate compared to patients under 75.
Safety, tolerability, and efficacy of sofosbuvir plus ribavirin in elderly patients infected with hepatitis C virus genotype 2. Nishida N, Kono M, Minami T et al. Dig Dis. 2016;34(6):632-639 Epub 2016 Oct 17.
Increased risk of NHL in HCV/HBV co-infected HIV patients receiving ART
HIV patients co-infected with HBV or HCV and who are receiving anti-retroviral therapy (ART) are at an increased risk of non-Hodgkin lymphoma (NHL).
This was the conclusion by the Collaboration of Observational HIV Epidemiological Research Europe (COHERE), which studied 52,479 treatment-naive patients of whom 1,339 had chronic HBV and 7,506 had HCV. A total of 40,219 later started ART. The median follow-up was 13 months for treatment-naïve patients and 50 months for those receiving ART.
A total of 252 treatment-naïve patients and 310 ART treated patients developed NHL, with incidence rates of 219 and 168 cases per 100,000 person-years, respectively. The hazard ratios for NHL with HBV and HCV infection were 1.33 and 0.67, respectively, in treatment-naive patients and 1.74 and 1.73, respectively, in ART treated patients.
Chronic hepatitis B and C virus infection and risk for non-Hodgkin lymphoma in HIV-infected patients: a cohort study. Wang Q, De Luca A, Smith C et al. Ann Intern Med. 2016 Oct 18 [Epub ahead of print]
Comparing the relative renal safety of HBV drugs
A new animal study has looked at the relative safety of four anti-HBV drugs against HBV, with respect to kidney function and toxicity.
Researchers at Novartis Institutes for BioMedical Research, Basel, administered telbivudine, tenofovir, adefovir or entecavir to male Spraque-Dawley rats once daily for four weeks by oral gavage at about 10 and 25-40 times the human equivalent dose. Main assessments included markers of renal toxicity in urine, magnetic resonance imaging (MRI) of kidney function, histopathology and electron microscopic examination.
Administration of adefovir at 11 mg/kg and 28mg/kg for four weeks caused functional and morphological kidney alterations in a time- and dose-dependent manner, affecting mainly the proximal tubules and suggesting a mechanism of toxicity related to mitochondrial degeneration/depletion.
For the low dose of 300mg/kg of tenofovir, minor kidney effects such as nuclear enlargement in the tubular epithelium, and hyaline droplets accumulation were detected, which was also observed for the low dose (11mg/kg) of adefovir. No assessments could be done at the higher dose of 600/1,000mg/kg tenofovir due to gastrointestinal tract toxicity, which prevented treatment of the animals for longer than one week.
Entecavir at 1mg/kg and 3mg/kg and telbivudine at 600 mg/kg and 1,600mg/kg caused no toxicologically relevant effects on the kidney.
Comparative renal safety assessment of the hepatitis B drugs, adefovir, tenofovir, telbivudine and entecavir in rats. Uteng M, Mahl A, Beckmann N et al. Toxicol Sci. 2016 Oct 13 [Epub ahead of print]
People with mental disorders at increased risk of HIV/HCV co-infection
A new review suggests that people with psychiatric diseases may be at an increased risk of HIV/HCV co-infection
The authors, from the University of Barcelona, found that the prevalence of HCV infection among HIV-infected patients is high ranging from 50% to 90%. Patients with psychiatric diseases have also an increased risk for HIV/HCV co-infection.
The most effective strategy to decrease HCV-related morbidity and mortality in co-infection is to achieve viral eradication. Although psychiatric symptoms often appear during antiviral treatment and may be associated with the use of interferon-alpha, recent evidence suggests that many patients with comorbid mental and substance use disorders can be treated safely.
Recent data indicate that interferon-alpha-induced psychiatric side effects have a similar prevalence in HIV/HCV co-infected patients to mono-infected patients and they can be managed and even prevented successfully with psychopharmacological strategies in the frame of a multidisciplinary team. New antivirals offer interferon-free therapies for this specific population.
Mental disorders in HIV/HCV coinfected patients under antiviral treatment for hepatitis C. Martin-Subero M, Diez-Quevedo C. Psychiatry Res. 2016 Sep 26; 246:173-181 Epub ahead of print]
Elbasvir/grazoprevir tablet effective in previously failed HCV
The combination of elbasvir and grazoprevir, with or without ribavirin, was effective in HCV patients failed by previous treatment, a large international study reported.
The study, at 65 centres in Europe, Asia, and Central and North America, assessed the effects of 12 or 16 weeks of a once daily tablet of elbasvir plus grazoprevir, with or without twice-daily ribavirin, in patients with HCV genotype one, four or six. There were 420 patients, of whom 35% had cirrhosis and 64% had a null or partial response to peg-interferon and ribavirin.
With 12 weeks of treatment, an SVR12 was achieved by 92.4% of patients given elbasvir and grazoprevir and 94.2% of patients given elbasvir and grazoprevir with ribavirin.
With 16 weeks of treatment, SVR12 was achieved by 92.4% of patients given elbasvir and grazoprevir and 98.1% of patients given elbasvir and grazoprevir with ribavirin.
Among patients treated for 12 weeks without ribavirin, virologic failure occurred in 6.8%, none, and 12.5% of patients with HCV genotype 1a, 1b, or four infection, respectively.
Also among patients given elbasvir and grazoprevir for 12 weeks, virologic failure occurred in none of the patients infected with HCV genotype 1, and 7.5% of those with genotype 4.
Among patients treated for 16 weeks who received ribavirin, there were no incidences of virologic failure. The treatment was generally well tolerated.
Effectiveness of elbasvir and grazoprevir combination, with or without ribavirin, for treatment-experienced patients with chronic hepatitis C infection. Kwo P, Gane E, Peng CY et al. Gastroenterology. 2016 Oct 5 [Epub ahead of print]
Diet and exercise independently improve fat oxidation in NAFLD
New research shows diet and exercise training have specific benefits on fat metabolism in patients with non-alcoholic fatty liver disease (NAFLD).
In a study at the University of Queensland, 10 NAFLD patients were randomised to circuit exercise training (EX) for three hours a week, and six patients to dietary energy restriction (ER). Respiratory quotient (RQ) and whole-body fat oxidation rates (Fatox) were determined by indirect calorimetry under basal, insulin-stimulated and exercise conditions. Severity of disease and steatosis was determined by liver histology; hepatic Fatox was estimated from plasma β-hydroxybutyrate concentrations; cardiorespiratory fitness was expressed as VO2peak.
Hepatic steatosis and NAFLD activity scores decreased with ER but not with EX. β-hydroxybutyrate concentrations increased significantly in response to ER but remained unchanged in response to EX. Basal RQ decreased in response to EX, while this change was not significant after ER. Maximal Fatox during aerobic exercise improved with EX but not with ER. The increase in β-hydroxybutyrate concentrations was correlated with the reduction in hepatic steatosis.
Independent effects of diet and exercise training on fat oxidation in non-alcoholic fatty liver disease. Croci I, Byrne NM, Chachay VS et al. World J Hepatol. 2016 Sep 28;8(27):1137-1148
HBV may reduce risk of stroke
New evidence suggests people with HBV are less likely to develop acute ischaemic stroke (AIS).
Researchers at China Medical University Hospital used a Taiwan national insurance claims data set of 1m patients to study 22,303 patients with HBV and 89,212 matched controls from the beginning of 2000 to the end of 2006. Both groups were followed up until the appearance of AIS or the end of 2011.
After adjusting for the relevant covariates, the HBV group exhibited a lower AIS risk (adjusted hazard ratio 0.77) compared with the controls at the end of follow-up. Under the condition of no co-morbidities, patients with HBV had a lower AIS risk compared with the controls (adjusted hazard ratio 0.65). In three age-stratified subgroups, HBV was correlated with a significantly diminished risk of AIS (adjusted hazard ratios at age ≤ 49 years 0.57; at age 50-64 years 0.65; and at age ≥ 65 years 0.96).
The study authors suggest that although a decrease in AIS risk was noted in the patients with HBV, preventing the development of AIS in this population warrants further attention.
Association of hepatitis B virus infection with decreased ischemic stroke. Tseng CH, Muo CH, Hsu CY et al. Acta Neurol Scand. 2016 Nov; 143(5): 339-345
HCV patients have body composition changes
Chronic HCV patients have both an acquired type of lipodystrophy (particularly in the trunk region) and a reduced bone mineral density (BMD) compared to controls.
These were the findings of researchers at Bucharest’s Carol Davila University of Medicine and Pharmacy, who assessed 60 chronic HCV patients and 60 healthy controls by Dual Energy X-Ray Absorptiometry.
Total fat mass, trunk fat mass and per cent body fat were lower in the HCV patients. Several risk factors were associated with the reduced fat mass: low BMI, cigarette smoking and peg-interferon alpha 2a plus ribavirin treatment. Peg-interferon alpha 2a and ribavirin treatment negatively correlated with lean body parameters, especially in male patients. BMD was lower when compared to controls and was correlated with low body mass index, cigarette smoking and peg-interferon alpha 2a and ribavirin treatment.
Body composition changes in patients with chronic hepatitis C. Barbu EC, Chiţu-Tișu CE, Lazăr M et al. J Gastrointestin Liver Dis. 2016 Sep; 25(3):323-9
ElastPQ technique accurately assesses liver fibrosis in HCV
The ElastPQ technique is reliable and accurate for assessing liver fibrosis in HCV, a new study reported.
Researchers at Italy’s Medical School University of Pavia assessed the performance in staging liver fibrosis of the updated ElastPQ technique (EPIQ7 ultrasound system) in a "real life" setting. A total of 278 chronic HCV patients referred for liver stiffness measurement with the FibroScan 502 Touch device also underwent measurements with the ElastPQ technique.
For the assessment of significant fibrosis, advanced fibrosis and cirrhosis, respectively, the cutoffs of 7, 9.5 and 12kPa were used. The diagnostic performance of ElastPQ was assessed using the area under the ROC curve analysis and was evaluated overall and for cases with (a) 10 measurements and IQR/M</=30%, (b) five measurements and IQR/M </=30%, (c) 10 measurements and IQR/M>30%, (d) five measurements and IQR/M>30%.
The optimal cutoffs of ElastPQ for significant fibrosis, advanced fibrosis and cirrhosis were 6.43, 9.54 and 11.34 kPa, respectively. For measurements with an IQR/M</=30%, there was no statistically significant decrease in sensitivity between 10 and five measurements.
Accuracy of the ElastPQ technique for the assessment of liver fibrosis in patients with chronic hepatitis C: a "real life" single center study. Ferraioli G, Maiocchi L, Lissandrin R et al. J Gastrointestin Liver Dis. 2016 Sep; 25(3):331-5
Chemotherapy patients with HBV markers need prophylactic antiviral therapy
Patients receiving chemotherapy who have serological markers of previous HBV infection remain at risk for reactivation, and need effective pre-emptive antiviral prophylaxis.
This is suggested by the results of a study at Athens University which retrospectively evaluated the medical records of 55 HBsAg-negative, anti-HBc-positive patients with haematological diseases or solid tumours who underwent immunosuppressive therapies and were referred because of positive baseline HBV serology or HBV reactivation.
Of the 55 patients, 31 received antiviral prophylaxis (group one), whereas 24 patients did not receive any anti-HBV agent (group two). The majority of patients had haematological malignancies and most of them received rituximab-containing regimens.
Lamivudine was used as antiviral prophylaxis in 13 of the 31 patients in group one. One patient in this group experienced HBV reactivation and was treated successfully with tenofovir add-on therapy.
All patients in group two experienced HBV reactivation and most of them were treated with tenofovir or entecavir as rescue therapy. Two of these patients (one of the tenofovir/entecavir subgroup and one of the lamivudine subgroup) eventually died because of hepatic failure despite rescue treatment.
The researchers conclude that screening of both anti-HBs and anti-HBc is mandatory before chemotherapy. Pre-emptive antiviral prophylaxis, including lamivudine, is highly effective in all subgroups of such patients, whereas deferring treatment upon HBV reactivation is not enough to rescue all cases.
Efficacy of prophylactic antiviral therapy and outcomes in HBsAg-negative, anti-HBc-positive patients receiving chemotherapy: a real-life experience. Papadopoulos N, Deutsch M, Manolakopoulos S et al. Eur J Gastroenterol Hepatol. 2016 Sep 23 [Epub ahead of print]
Corticosteroids safe in rheumatologic patients with HBV markers
A new study suggests short episodes of corticosteroids seem to be safe in rheumatologic patients with markers of HBV.
The study followed 23 HBsAg or HBcore antibodies positive, anti-HBs negative patients who were hospitalised for a total of 73 times in the rheumatology department at Rambam Health Care Campus, Haifa, Israel, and who each received seven days’ treatment with IV corticosteroids. Eighteen were HBsAg positive. The mean methylprednisolone dose was 33.9 mg/day. Concomitant therapy included disease-modifying anti-rheumatic drugs (DMARDs) in 15, low-dose corticosteroids in eight, and biologicals in 10. Serum HBV DNA was detected at baseline in seven patients.
Three HBsAg-positive patients treated with cyclophosphamide had HBV hepatitis flare-ups with elevated alanine aminotransferase (ALT). Two HBsAg-positive patients had reappearance of HBV DNA in serum after treatment with azathioprine and infliximab, respectively, but the ALT levels remained normal. Lamivudine therapy reduced the serum HBV DNA and improved ALT levels in all patients. Corticosteroid therapy by itself did not trigger exacerbations of HBV. No HBV reactivation occurred in lamivudine-treated patients after recurrent exposure to biologicals or cyclophosphamide.
Safety of corticosteroid treatment in rheumatologic patients with markers of hepatitis B viral infection: pilot evaluation study. Braun-Moscovici Y, Braun M, Saadi T et al. J Clin Rheumatol. 2016 Oct; 22(7): 364-8
Injecting drug use is a major global risk factor for HCV, HBV and HIV
A new analysis of international data shows injecting drug use (IDU) is a major contributor to the global burden of HCV, HBV and HIV.
Previous estimates of the burden of these diseases among people who inject drugs have not included estimates of the burden attributable to the consequences of past injecting. Therefore, a team of researchers from Australia, the UK and the USA used the Global Burden of Disease Study and United Nations data to study this risk factor.
They estimated 10million disability-adjusted life-years (DALYs) were attributable to previous exposure to HIV, HBV, and HCV via IDU, a four-times increase since 1990.
In total, in 2013, IDU was estimated to cause 4% of DALYs due to HIV, 1.1% of DALYs due to HBV, and 39.1% of DALYs due to HCV. The IDU-attributable HIV burden was highest in low-to-middle-income countries, and the IDU-attributable HCV burden was highest in high-income countries.
The researchers suggest that effective interventions to prevent and treat these important causes of health burden need to be scaled up.
Estimating the burden of disease attributable to injecting drug use as a risk factor for HIV, hepatitis C, and hepatitis B: findings from the Global Burden of Disease Study 2013. Degenhardt L, Charlson F, Stanaway J et al. Lancet Infect Dis. 2016 Sep 21 [Epub ahead of print]
Hepatic amyloidosis as a rare differential diagnosis of progressive liver failure
German researchers have reported a case of hepatic amyloidosis as a rare differential diagnosis of progressive liver failure.
A 63-year-old man presented with newly diagnosed ascites to the researchers’ department. The patient reported occasional alcohol consumption. Viral hepatitis, genetic-metabolic causes as well as hepatic vascular disorders were excluded and ultrasound did not show any signs of liver cirrhosis or intraabdominal malignancy.
Initially, alcoholic hepatitis was suspected. Because of the rapid deterioration of liver function, however, transjugular liver biopsy was performed, showing light chain amyloidosis of kappa isotype.
The researchers suggest that, as the diagnosis of hepatic amyloidosis is challenging, early liver biopsy is mandatory in patients with unexplained acute or chronic liver disease to exclude rare diseases with high mortality.
Hepatic amyloidosis as a rare differential diagnosis of progressive liver failure. Bettinger D, Lutz L, Schultheiß M et al. Dtsch Med Wochenschr. 2016 Sep;141(19):1387-1389
Six weeks sofosbuvir plus ribavirin is not effective in HCV
While six weeks of sofosbuvir and ribavirin therapy was safe and well tolerated in HCV patients, its efficacy was sub-optimal, a study concluded.
In this open-label study conducted in Australia and New Zealand, 19 adults with recent HCV (68% genotype 1; duration of infection median 37 weeks) received sofosbuvir 400mg daily and weight-based ribavirin for six weeks.
Four reported a symptomatic HCV seroconversion illness, including two with jaundice. At baseline, the median HCV RNA was 5.4 log10 IU/mL and at the end-of-treatment, it was non-quantifiable in 89%. SVR4 and SVR12 were 42% and 32%, respectively.
Treatment failure was because of non-response in two, post-treatment relapse in nine, re-infection in one, and with one loss to follow up.
The regimen was well tolerated with minimal haematological toxicity. SVR12 was related to baseline HCV RNA (≤6 log10 IU/mL, p=0.018) and early on-treatment viral kinetics.
The researchers suggest that further research is needed to determine whether more potent interferon-free direct-acting antiviral regimens will allow treatment duration to be shortened in recent, predominantly asymptomatic, HCV infection.
Sofosbuvir and ribavirin for six weeks is not effective among people with recent HCV infection: The DARE-C II study. Martinello M, Gane E, Hellard M et al. Hepatology. 2016 Sep 17 [Epub ahead of print]
UK patients who have liver transplants abroad get poorer management
A small number of UK citizens are undergoing liver transplants abroad but their management is of a lower standard than in the UK.
These were the conclusions of researchers at Sheffield’s Royal Hallamshire Hospital, who sent questionnaires to all seven UK liver transplant units enquiring about liver patients receiving transplant abroad. Six of the seven centres responded.
A total of 12 patients were identified as having undergone liver transplantation overseas. The top destinations were India, China and Egypt.
Four units responded to questions regarding pre-transplant screening. One unit reported HBV and HCV screening not taking place. Four units responded to questions regarding post-transplant antimicrobial therapy. This revealed examples of patients inappropriately not receiving valganciclovir, co-trimoxazole, anti-fungal treatment and HBV immunoglobulins.
The researchers add that information transfer between overseas and UK based transplant teams is poor.
A questionnaire based assessment of numbers, motivation and medical care of UK patients undergoing liver transplant abroad. Winter BK, Odedra A, Green S. Travel Med Infect Dis. 2016 Sep 14 [Epub ahead of print]
Many vulnerable people do not return for hep screening results
More than a third of vulnerable people screened for HBV, HCV, HIV and syphilis at out-of-hospital sites, did not return for result, a study in Paris has revealed.
Researchers at nine out-of-hospital screening mobile sites in Paris explored the rates of these infections amongst 341 vulnerable people who were mostly intravenous drug users, sex workers or homeless.
The proportion of failure to return for results was 38.75%. In multivariate analysis, unemployment was significantly associated with failure to return (odds ratio 4.29), as well as having been screened in the past (odds ratio 4.32). And 18.03% of the patients had a false perception of an immunization against HBV.
In multivariate analysis, having a place of residence protected against a false perception (odds ratio 0.33), while being screened in the past enhanced the risk of a false perception (odds ratio 3.28).
The researchers suggest that using technologies, such as phone texting, might be a partial solution along with rapid diagnostic tests. More information and explanation of the results should be provided, along with specific anti-HBV vaccination campaigns targeting these specific populations.
Out-of-hospital screening for HIV, HBV, HCV and syphilis in a vulnerable population, a public health challenge. Legoupil C, Peltier A, Henry Kagan V et al. AIDS Care. 2016 Sep 14:1-3 [Epub ahead of print]
“Acceptable outcomes” for liver transplant patients who have cardiac surgery
Liver transplant patients who receive subsequent cardiac surgery have acceptable short-term and long-term outcomes, researchers have concluded.
The researchers, from the University of Alabama at Birmingham School of Medicine, analysed data on 43 patients (median age 60) who underwent cardiac operations at 63 months, on average, after their liver transplants.
There were three operative deaths and 24 late deaths. The patients with a preoperative Model for End-Stage Liver Disease (MELD) score of 13.8 or less had significantly greater survival rates than those with a MELD score greater than 13.8. Patients with a postoperative MELD score of 17 or less had significantly greater survival rates than those with a MELD score greater than 17.
Further analyses showed that postoperative peak creatinine levels were statistically significant predictors of death (relative risk 1.8). The one, five, and 10 year Kaplan-Meier survival rates were 90%, 51%, and 35%, respectively; postoperative mortality rates followed a constant phase model with a hazard of death of 10% per year.
Outcomes of patients who undergo cardiac surgical procedures after liver transplantation. Harrington PB, McAlexander WW, Bryant AS et al. Ann Thorac Surg. 2016 Sep 9 [Epub ahead of print]
No difference in efficacy/safety of sorafenib for elderly HCC patients
Elderly patients with advanced hepatocellular carcinoma (HCC) who were treated with sorafenib had similar clinical outcomes and toxicity rates to their younger counterparts, according to a UK study.
A total of 190 HCC patients who were treated with sorafenib at King's College Hospital, London, were divided into two groups: (A) 151 patients aged up to 75 and (B) 39 patients older than 75.
There was no significant difference in overall survival (OS) and time to treatment failure (TTF) between the two groups (7.1 months versus 10.4 months; and 4.2 months versus 5.6 months, respectively). The incidence of toxicities at all grades and dose reductions were comparable between the two groups.
In a multivariate setting, patients with Child-Pugh B scores at baseline were associated with a higher risk of death (adjusted hazard ratio 2.17) and treatment failure (adjusted hazard ratio 4.64) and had shorter OS and TTF compared with patients with a Child-Pugh A.
The researchers concluded that age alone should not be a discriminating factor for the management of advanced HCC with sorafenib.
Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: age is not a problem. Ziogas DC, Papadatos-Pastos D, Thillai K et al. Eur J Gastroenterol Hepatol. 2016 Sep 10 [Epub ahead of print]
High rate of HBV breakthrough in elderly NHL patients on rituximab
Researchers have reported a high rate of HBV breakthrough amongst elderly non-Hodgkin lymphoma (NHL) patients receiving rituximab-based chemotherapy.
The researchers, at Milan’s Luigi Sacco Hospital, evaluated 85 newly diagnosed NHL patients aged over 65 with resolved HBV infection who received rituximab-containing chemotherapies. All received lamivudine. HBV DNA was checked at baseline, every four weeks, for one year after completing the rituximab containing regimens.
Nine patients had HBV reactivation and HBV-related hepatitis. All received entecavir and recovered without consequences. HBV reactivation was more likely to occur after an average of five R-CHOP cycles or during fludarabine.
The researchers concluded that the rate of viral breakthrough was high, considering that the patients were HBV DNA negative at baseline. They suggested that lamivudine prevention may not be sufficient in this population.
High rate of hepatitis B viral breakthrough in elderly non-Hodgkin lymphomas patients treated with Rituximab based chemotherapy. Castelli R, Ferraris L, Pantaleo G et al. Dig Liver Dis. 2016 Aug 20 [Epub ahead of print]
HCV patients satisfied with clinical pharmacists
A new US study suggests patients with HCV appear to be highly satisfied with the treatment provided by clinical pharmacists.
Researchers at the University of Massachusetts Medical School offered an anonymous patient satisfaction survey to patients who were initiating or receiving HCV treatment under the care of a clinical pharmacist.
Sixty-four patients completed 77 (24 pharmacist and 53 prescriber) patient satisfaction surveys. The patients reported high levels of satisfaction with the pharmacist and prescribers. All 24 patients ranked overall satisfaction with services provided by pharmacists as 'great', and 36 of 52 patients ranked overall satisfaction with services provided by prescribers as 'great'. Patients supported the inclusion of a clinical pharmacist on health care teams for other disease states.
Patient satisfaction with the clinical pharmacist and prescribers during hepatitis C virus management. Martin MT, Faber DM. J Clin Pharm Ther. 2016 Aug 31 [Epub ahead of print
No mother-to-child HCV transmission among dental patients
A new study has not found any mother-to-child transmission of HCV among patients attending a dental hospital in Scotland.
The study was undertaken among children, accompanying parents and household contacts attending a general anaesthetic assessment clinic at Glasgow Dental Hospital and School. Children were asked to provide an oral fluid specimen for HCV testing. Accompanying adults were asked to provide demographic data on the child and information on familial risk factors for HCV infection using a standardised questionnaire. Birth mothers were also asked to provide an oral fluid specimen.
Between June 2009 and December 2011, samples were collected from 2,141 children and 1,698 mothers. None of the samples from the children were HCV seropositive but 16 (0.9%) of the specimens from mothers were HCV antibody positive.
The researchers summarised that the prevalence of HCV seropositivity in the birth mothers of the children was similar to that estimated in the general population served by the hospital and showed no evidence of mother-to-child transmission of HCV.
The seroprevalence of hepatitis C virus infection among children and their mothers attending for dental care in Glasgow, Scotland, United Kingdom. O'Leary M, Bagg J, Welbury R et al. J Infect Public Health. 2016 Aug 24 [Epub ahead of print]
NAFLD rates higher in people with metabolic abnormalities
The prevalence of non-alcoholic fatty liver disease (NAFLD) and the rate of advanced fibrosis are significantly high among individuals with metabolic abnormalities, a new study found.
Among 11,674 individuals in NHANES III, a large United States population database, the prevalence of NAFLD was 18.2%. Individuals with metabolic abnormalities demonstrated a higher prevalence. These included metabolic syndrome (43.2%), increased waist circumference (31.2%), impaired fasting glucose/diabetes (41.2%), high triglyceride level (34.7%), low high-density lipoprotein (27.8%), and high blood pressure (29.2%).
The individuals with metabolic syndrome had significantly higher NAFLD prevalence compared with controls (adjusted odds ratio 11.5). The severity of hepatic steatosis increased with higher number of metabolic abnormalities. Among individual metabolic abnormalities, increased waist circumference, impaired fasting glucose/diabetes, high triglyceride, and low high-density lipoprotein levels were found to be independently associated with NAFLD.
Individuals with impaired fasting glucose/diabetes and those with five metabolic abnormalities had higher rates of advanced fibrosis (18.6% and 30.3%, respectively). The prevalence of NAFLD among individuals without any metabolic abnormalities was 6.1%.
The association between nonalcoholic fatty liver disease and metabolic abnormalities in the United States population. Jinjuvadia R, Antaki F, Lohia P et al. J Clin Gastroenterol. 2016 Aug 31. [Epub ahead of print]
Managing HCV in a UK outreach DTU “feasible and cost effective”
A UK study showed outreach testing and treating HCV in a drug treatment unit (DTU) could be both feasible and cost effective.
All persons attending a London DTU were offered HCV testing, and where appropriate follow-up and treatment by a specialist nurse at the DTU. Of 321 persons eligible, 216 were screened, 89 were HCV positive and 66 had confirmatory evidence of viraemia. All were infected with either HCV genotype 1 or 3.
Treatment was initiated in 29 people, 22 with interferon-based regimens and seven with direct-acting antiviral only treatments. Following initial treatment 21 (72%) achieved SVR12.
The study authors, from Imperial College, London, estimated that the programme represented an average per-patient cost-saving of £2,498 and a quality-adjusted life year (QALY) gain of 4.10 over a lifetime. In a hypothetical scenario of all oral DAA treatment, an incremental cost per QALY of £1,029 was estimated.
The cost impact of outreach testing and treatment for hepatitis C in an urban drug treatment unit. Selvapatt N, Ward T, Harrison L et al. Liver Int. 2016 Aug 27 [Epub ahead of print]
HCV is associated with Sjögrens Syndrome
People with HCV are at a greater risk of the autoimmune disorder, Sjögrens Syndrome (SS), a large Taiwanese study has confirmed.
Researchers, who also found an association between HBV and SS in men, used data from the Taiwan National Health Insurance claims database, entered between 2000 and 2011.
They identified 9,629 SS patients without other concomitant autoimmune diseases and 38,516 sex- and age-matched controls without the condition.
The risk of SS was higher in patients with HCV than in those without chronic viral hepatitis (odds ratio 2.49). Conversely, HBV infection was not associated with SS (odds ratio1.10). Younger HCV patients were at a higher risk for SS (<55 years odds ratio 3.37; ≥55 years odds ratio 2.20).
Men with HCV were at a greater risk for SS (women odds ratio 2.26; men odds ratio 4.22). Only men with chronic HBV exhibited a higher risk of SS (odds ratio 1.61).
Association of Sjögrens Syndrome in patients with chronic hepatitis virus infection: a population-based analysis. Yeh CC, Wang WC, Wu CS et al. PLoS One. 2016 Aug 25;11(8): e0161958
More deaths than normal amongst cured HCV patients in Scotland
Scottish patients who were successfully treated for HCV had a higher mortality rate than the general population, driven by drug-and alcohol-related causes and liver cancer.
These were the conclusions of a group from Aberdeen, Dundee, Edinburgh and Glasgow who used a Scottish national database to identify 1824 individuals with HCV who attained a sustained viral response (SVR) between 1996 and 2011 and were followed for an average 5.2 years.
In total, there were 78 deaths. All-cause mortality was 1.9 times more frequent for SVR patients than the general population (standardised-mortality-ratio 1.86).
Significant cause-specific elevations were seen for death due to primary liver cancer (standardised-mortality-ratio 23.50), and death due to drug-related causes (standardised-mortality-ratio 6.58). These two causes accounted for 66% of the total excess death observed.
All of the modifiable characteristics associated with increased mortality were markers either of heavy alcohol use or injecting drug use. Individuals without these behavioural markers (32.8% of cohort) experienced equivalent survival to the general population (standardised-mortality-ratio 0.70).
Mortality in hepatitis C patients who achieve a sustained viral response compared to the general population. Innes H, McDonald S, Hayes P et al. J Hepatol. 2016 Aug 18 [Epub ahead of print]
HEV outbreaks remain a global health problem
A systematic review of published literature has concluded that whilst HEV outbreaks are not new, they remain a continuous global health problem.
An international team of reviewers found that HEV outbreaks have mainly been reported from Asian and African countries and only a few from European and American countries. India has the highest number.
HEV genotypes 1 and 2 were responsible for most large outbreaks in developing countries. During the outbreaks in developing countries, significantly more pregnant women died.
Outbreaks have occurred in open and closed populations. The control measures mainly depend on improvement of sanitation and hygiene.
The global burden of hepatitis E outbreaks: a systematic review. Hakim MS, Wang W, Bramer WM et al. Liver Int. 2016 Aug 20 [Epub ahead of print]
Limited HBV/HCV treatment access for vulnerable groups in Europe
Many vulnerable patients, including refugees, have limited access to HCV and HBV treatment across six major European countries (including the UK).
Researchers from the Netherlands investigated access to treatment for chronic HBV and HCV among six vulnerable patient/population groups at risk of infection: undocumented migrants, asylum seekers, people without health insurance, people with state insurance, people who inject drugs, and people abusing alcohol. The researchers sent an online survey to 235 experts in gastroenterology, hepatology and infectious diseases in six EU countries: Germany, Hungary, Italy, the Netherlands, Spain and the UK. The 64 responses showed differences in access between and within countries for all groups except people with state insurance. Most professionals, other than in Spain and Hungary, reported no or few restrictions for people who inject drugs.
The majority in Hungary and Spain reported significant/complete treatment restriction for all groups, while in Italy there were no/few restrictions. In the UK and Spain, undocumented migrants and people without health insurance were significantly or completely restricted. Opinion about undocumented migrants in Germany and the Netherlands was divergent.
The researchers conclude that their findings suggest a low awareness, or lack, of entitlement guidance among clinicians. Expanding treatment access among risk groups will contribute to reducing chronic viral hepatitis-associated avoidable morbidity and mortality.
Limited access to hepatitis B/C treatment among vulnerable risk populations: an expert survey in six European countries. Falla AM, Veldhuijzen IK, Ahmad AA et al. Eur J Public Health. 2016 Aug 19 [Epub ahead of print]
Study questions isolation of HCV patients during haemodialysis
A literature review has cast doubt on whether isolating HCV-infected patients during haemodialysis has any effect on transmission rates.
The Universidad Peruana Cayetano Heredia, Lima, Peru, found only one appropriate study. It covered 12 centres: four used dedicated haemodialysis machines for HCV-infected patients and eight used non-dedicated machines. There were 593 patients enrolled. One centre was excluded after randomisation. Random sequence generation was not described and allocation concealment was not performed. Participants and personnel were not blinded and blinding of outcome assessors was not reported.
Only 74.5% of the patients were followed for nine months; and 47.3% were followed for an additional nine months. The authors only reported one outcome, measuring the difference in incidence of HCV in both groups. The authors did not consider the exposure time, to determine the adjusted rate of seroconversion risk/patient-year.
The study reported that the incidence of HCV infection during the first follow-up period (nine months) was 1.6% in the dedicated group, and 4.7% in the non-dedicated group (risk ratio 0.34). During the second 18 month follow-up the incidence was 1.3% in the dedicated group and 5.8% in the control group (risk ratio 0.22).
The reviewers wrote, “we found no differences in terms of the number of participants developing HCV infection when comparing the dedicated group with the usual care. Moreover, the evidence was of very low quality, which means that we have very little confidence in the effect estimate”. They concluded that the benefits and harms of isolating HCV-infected patients from other patients during haemodialysis are uncertain.
Isolation as a strategy for controlling the transmission of hepatitis C virus (HCV) infection in haemodialysis units.Bravo Zuñiga JI, Loza Munárriz C, López-Alcalde J. Cochrane Database Syst Rev. 2016 Aug 11;8 [Epub ahead of print]
Successful responses with Peg-INF for HCV patients on haemodialysis
In a new study amongst haemodialysis patients with HCV, pegylated interferon (Peg-INF) monotherapy resulted in high virological responses and was well-tolerated.
Researchers at New Delhi’s All India Institute of Medical Sciences studied 80 patients on dialysis with HCV infection who were treated with Peg-INF monotherapy. Those with genotype 1 and 4 were given 12 months therapy while those with genotypes 2 and 3 had six months. Mean time from diagnosis of HCV infection and the treatment start was 10.7 months.
Of the 80 patients, 43 had rapid virological responses (RVRs), while 49 had early virological and end of treatment responses. There was no difference related to genotype and 54 percent had sustained virological responses.
All patients had mild flu-like symptoms, 64 required increases in erythropoietin doses, 28developed leukopenia (three treatment-limiting) and 16 developed thrombocytopenia (one treatment-limiting). Five developed tuberculosis, five bacterial pneumonia, and one bacterial knee monoarthritis. None of the patients developed depression.
Pegylated interferon monotherapy for hepatitis C virus infection in patients on hemodialysis: A single center study. Agarwal SK, Bhowmik D, Mahajan S et al. Indian J Nephrol. 2016 Jul-Aug;26(4):244-51
Routine testing gives earlier HCV detection in HIV-positive gay men
Routine anti-HCV testing at a sexually transmitted infection (STI) outpatient clinic led to earlier HCV detection among HIV-positive men who have sex with men (MSM).
In 2007, routine HCV antibody testing was introduced for MSM with an HIV-positive or unknown status attending a Dutch STI outpatient clinic. Researchers evaluated whether this screening resulted in additional and earlier HCV diagnoses among MSM who also attend HIV clinics.
At first STI consultation, HIV-positive MSM and MSM opting-out of HIV testing (HIV-status-unknown) were tested for HCV antibodies (anti-HCV). During follow-up consultations, only previously HCV-negative men were tested. Retrospectively, STI clinic and HIV clinic HCV diagnosis dates were compared.
At first consultation, 112 of 1,742 HIV-positive and three of 446 HIV-status-unknown MSM tested anti-HCV-positive. On follow-up, 32 HIV-positive MSM became anti-HCV-positive. Four of 34 HIV-positive MSM notified by their sexual partner of HCV tested anti-HCV-positive. Of 163 HIV-positive MSM with HCV antibodies, 78 reported a history of HCV.
HCV diagnosis data at the HIV clinic was requested for the remaining 85 MSM and available for 54 MSM. Of these 54, 28 were diagnosed with HCV at the STI clinic and seven concurrently with HIV. At their next scheduled HIV clinic consultation, three HCV cases probably would have been missed, the researchers suggested.
Earlier detection of hepatitis C virus infection through routine hepatitis C virus antibody screening of human immunodeficiency virus-positive men who have sex with men attending a sexually transmitted infection outpatient clinic: a longitudinal study. van Rooijen M, Heijman T, de Vrieze N et al. Sex Transm Dis. 2016 Sep;43(9):560-5
Anti-viral therapy may cut sexual desire in HCV patients
Many HCV patients – especially men – receiving some anti-viral therapies lose sexual desire.
A total of 181 HCV patients at Taiwan’s China Medical University Hospital tertiary medical centre received peg-interferon (PegIFN)α2a or PegIFNα2b plus ribavirin (RBV), according to response-guide therapy for 24 to 48 weeks. Those with decreased sexual desire before PegIFNα plus RBV were excluded.
All were evaluated using the Mini-International Neuropsychiatric Interview and the 21-item Beck Depression Inventory (BDI). The 21st item of the BDI was used to evaluate decreased sexual desire.
During therapy, 124 of the 181 patients had decreased sexual desire. The BDI score peaked at 14.8 weeks and the severity was greatest at 16 weeks. The average score of the 21st item of the BDI correlated with decreased sexual desire. Depression history and the prevalence of subsequent major depressive disorder after anti-viral therapy was correlated to reduced sexual desire. Male patients complained more significantly than females.
Anti-viral therapy and decreased sexual desire in patients with chronic hepatitis C. Hsiao PJ, Hsieh PF, Chou EC et al. PLoS One. 2016 Aug 9;11(8): e0160450
No added benefit with nurse-led treatment for HCV drug injectors
Nurse-led initiations of antiviral therapy have not lead to an increased uptake or adherence with treatment among people with HCV who inject drugs.
A study involving UK community clinics in London and Surrey compared nurse- and physician-initiated antiviral therapy with pegylated interferon and ribavirin.
Despite easy access to antiviral therapy, treatment uptake was poor, with no significant difference between the groups. The proportion of participants initiating treatment during follow-up was 10% with nurse-initiated (6/62) and 9% with physician-initiated (6/76) therapy. Adherence was similar in both groups, with only one patient in each not adhering to therapy. There were no serious adverse events, but interferon-related side effects were common. Drug and alcohol use did not change during therapy.
Community nurse-led initiation of antiviral therapy for chronic hepatitis C in people who inject drugs does not increase uptake of or adherence to treatment. Lewis H, Kunkel J, Axten D et al. Eur J Gastroenterol Hepatol. 2016 Aug 3. [Epub ahead of print]
High prevalence of cirrhosis and fibrosis in type 2 diabetics
People with type 2 diabetes often have undiagnosed advanced fibrosis and cirrhosis, a new study suggests (1).
Researchers at Pontificia Universidad Católica de Chile, Santiago, studied 145 type 2 patients (median age 60, mean BMI 29.6 kg/m2 and mean diabetes duration 7.6 years).
There was a high rate of liver steatosis (63.9%), advanced fibrosis assessed by NAFLD fibrosis score (12.8%) and evidence of liver cirrhosis assessed by MRI (6.0%). In a multivariate analysis GGT > 82 IU/L and no alcohol intake were independently associated to advanced fibrosis.
A literature review suggested that metformin may improve the survival of diabetic patients with liver cancer (2).
The reviewers, from Central South University, Changsha, China, found 11 studies involving 3,452 liver cancer patients. Metformin use was associated with better survival (hazard ratio 0.59) of liver cancer patients, and the beneficial effect persisted (hazard ratio 0.64) when the population was restricted to diabetic liver cancer patients. Adjusting for age, etiology, index of tumour severity and treatment of liver cancer, the association between metformin use and better survival of liver cancer patients was stable. Pooled hazard ratios ranged from 0.47 to 0.57.
The reviewers warned that the results should be interpreted with caution because of possible residual confounding.
1. High prevalence of undiagnosed liver cirrhosis and advanced fibrosis in type 2 diabetic patients. Arab JP, Barrera F, Gallego C et al. Ann Hepatol. 2016 Sep-Oct;15(5):721-8
2. Metformin use improves survival of diabetic liver cancer patients: systematic review and meta-analysis. Ma SJ, Zheng YX, Zhou PC et al. Oncotarget. 2016 Aug 2 [Epub ahead of print]
Many liver disease patients use complementary/alternative medicines
Many patients with liver disease use complementary and alternative medicines (CAMs) despite some being potentially hepatotoxic, often don’t tell their healthcare providers.
These were the findings of researchers at Duke University School of Medicine who analysed data from the 2012 [US] National Health Interview Survey. Of 647 adults with liver disease, 41% reported using CAMs in the prior year, compared with 33% of adults without liver disease. The most common modality was herbs and supplements (23%), and 3% of respondents reported consumption of a potentially hepatotoxic substance in the previous 30 days. Only a small proportion of CAM therapies were used specifically for liver disease, with milk thistle being the most common. Among respondents with liver disease, CAMs were used more commonly for anxiety or depression, fatigue, and substance use. The majority believed that these therapies improved health. Nearly one-third of therapies were not reported to healthcare providers, mostly because they don’t ask.
Complementary and alternative medicine use in United States adults with liver disease. Henson JB, Brown CL, Chow SC et al. J Clin Gastroenterol. 2016 Jul 29. [Epub ahead of print]
Risk factors for PegIFN-induced depression in HCV
A new study has identified the risk factors for, and clinical characteristics of, depressive states induced by pegylated interferon (PegIFN) therapies for HCV
In this Japanese multicentre study, 69 people with HCV who received PegIFN therapy were evaluated before treatment, using the Neuroticism-Extraversion-Openness Five-Factor Inventory and the List of Threatening Events Questionnaire. The Beck Depression Inventory (BDI) was also evaluated at baseline, two to four weeks after initiating therapy, and every four weeks thereafter.
During the study, 18 of the 69 patients developed a depressive state (BDI ≥ 10). A bimodal peak of onset was seen during early (two to eight weeks) and late (after 20 weeks) therapy phases. Moreover, baseline BDI scores (odds ratio 1.40) and neuroticism (odds ratio 1.14) were significant risk factors for developing a depressive state.
To determine the specific characteristics of this condition, the study researchers compared the BDI subscales between the "PegIFN-induced" and "general" depressive state reported previously. They found that the score at "somatic symptoms" were higher in the "PegIFN-induced" group.
The reviewers concluded PegIFN-induced depressive states most frequently developed during the first eight weeks of therapy, and that baseline BDI and neuroticism scores are risk factors for PegIFN-induced depressive state. The core symptoms of PegIFN-induced depressive state are different from those of "general" depression, they added.
Risk factors and clinical characteristics of the depressive state induced by pegylated interferon therapy in patients with hepatitis C virus infection: a prospective study. Kawase K, Kondo K, Saito T et al. Psychiatry Clin Neurosci. 2016 Jul 29 [Epub ahead of print]
Ribavirin remains useful for some HCV patients
In the era of direct-acting antivirals (DAAs), ribavirin continues to provide clinical benefit for defined groups of patients with HCV, a review has concluded.
Over the past two decades, ribavirin has been an integral component of HCV treatment, where it has been shown to improve the efficacy of pegylated interferon. However, write an international group of reviewers, because of to its treatment-limiting side effects and additive toxicity with interferon, the search for interferon- and ribavirin-free regimens has been underway.
The recent approvals of all-oral DAAs have revolutionised the HCV therapeutic landscape, and initially it was expected that the role of ribavirin with DAA regimens would be eliminated.
Yet reviewers say we have witnessed ribavirin retaining an important role in the optimal treatment of some subgroups, particularly those that historically have been considered the most difficult to cure.
Fortunately, it has also been recognized that the safety profile , of ribavirin is improved when co-administered with all-oral DAA combinations in the absence of interferon.
The reviewers summarise that, despite the antiviral mechanism of action of ribavirin being poorly understood, we now have a range of novel insights into the potential role of ribavirin in all-oral DAA HCV treatment.
Ribavirin revisited in the era of direct-acting antiviral therapy for hepatitis C virus infection. Feld JJ, Jacobson IM, Sulkowski MS et al. Liver Int. 2016 Jul 30 [Epub ahead of print]
Liver transplant patients more likely to develop cerebrovascular events
People receiving liver transplants (LTs) seem to have a considerably increased risk of cerebrovascular events (CBVEs), a new study concluded.
A new score (PROCAM-Stroke) estimates the 10-year risk of cerebrovascular events (CBVE) in a German standard population. Researchers, from Berlin’s Virchow Klinikum and Aachen’s University Hospital, retrospectively studied 313 LT patients. Six months after LT (T1) and 10 years after LT (T2) CBVE risk factors were recorded and PROCAM-stroke was calculated. Ten (T2) and 20 years (T3) after LT, the recipients were screened regarding CBVE. PROCAM-stroke estimates of CBVE were compared with the incidence of observed CBVE.
In both ten-year time frames the incidence of observed CBVE was higher than expected based on the PROCAM-stroke estimates: Six months - 10 years after LT (T1-T2): observed: 11, expected: 3.2; Ten years - 20 years after LT (T2-T3): observed: 7, expected: 3.4.
The researchers suggest that the progressive impairment of renal function in the long-term LT survivors may be one reason for the underestimation of CBVE in this patient group.
Cerebrovascular events in 20-years of follow-up after liver transplantation. an underestimated issue? Schoening W, Buescher N, Neidel N et al. Clin Transplant. 2016 Jul 22 [Epub ahead of print]
HCV patients report greater efficacy with sofosbuvir plus velpatasvir
Patients with HCV genotypes 2 and 3 reported significantly better outcomes with sofosbuvir plus velpatasvir (SOF/VEL) compared with those receiving SOF and ribavirin (RBV).
Patient-reported outcome (PRO) data were collected from 818 participants in the multinational ASTRAL-2 and ASTRAL-3 studies before, during and after treatment using four PRO instruments (SF-36v2, FACIT-F, CLDQ-HCV, WPAI:SHP), and compared between the SOF/VEL and SOF+RBV groups.
The rates of nearly all adverse events were lower in the RBV-free SOF/VEL group. The SOF/VEL group also experienced improvement of their PROs by treatment week four (+1.8% on average across all PROs) which continued throughout treatment (+4.1%) and post-treatment (+5.5%). In contrast, the SOF+RBV group had a modest decline in their PROs starting at treatment week four (up to -3.7%) which lasted until the end of treatment (up to -6.4%).
In multiple regression analysis, the association of a treatment regimen with end-of-treatment PROs was significant for nearly all PROs; the average beta was +5.0% for the use of the SOF/VEL (reference: SOF+RBV).
Ribavirin-free regimen with sofosbuvir and velpatasvir is associated with high efficacy and improvement of patient-reported outcomes in patients with genotypes 2 and 3 chronic hepatitis C: results from Astral-2 and 3 clinical trials. Younossi ZM, Stepanova M, Sulkowski M et al. Clin Infect Dis. 2016 Jul 20 [Epub ahead of print]
HCV increases risk of complications after total shoulder arthroplasty
Following total shoulder arthroplasty (TSA), patients with HCV are more likely to have such complications as infection, dislocation, fracture, revision TSA, systemic complications and blood transfusion.
These were the findings of US national data, compiled at the University of Virginia, and involving 1,466 HCV patients and 21,502 matched controls who underwent TSA.
The HCV patients, when compared with the controls, had greater odds of infection within three months (odds ratio 1.7), six months (odds ratio 1.7), and one year (odds ratio 2.1); revision TSA within one year (odds ratio 1.5) and two years (odds ratio 1.6); dislocation within one year (odds ratio 1.6); postoperative fracture within one year (odds ratio 1.8); systemic or medical complications within three months (odds ratio 1.3); and blood transfusion within three months (odds ratio 1.7).
The researchers say that although this study was able to identify increased odds of complications in patients with HCV, the mechanism by which these occur was likely not solely related to the virus, and was more likely related to a higher degree of case complexity in addition to other postoperative socioeconomic factors.
Is hepatitis C infection associated with a higher risk of complications after total shoulder arthroplasty? Cancienne JM, Dempsey IJ, Holzgrefe RE et al. Clin Orthop Relat Res. 2016 Jul 22 [Epub ahead of print]
HCV patients at increased risk of cardio-cerebrovascular disease
A large literature review and meta-analysis confirms that HCV-infected patients are at an increased risk of cardio-cerebrovascular disease (CCD).
Reviewers from three academic centres in Italy found 27 studies which showed a significantly increased CCD risk in 297,613 HCV patients as compared with 557,814 uninfected controls (odds ratio 1.428).
These results were confirmed when separately considering the risk of coronary artery disease (CAD, 20 studies, odds ratio 1.382) and of cerebrovascular disease (13 studies, odds ratio 1.485).
Similar results were confirmed when analyzing 21 studies reporting adjusted risk estimates (odds ratio 1.448) and when, after excluding studies defining CAD as positive angiographic or electrocardiographic evidence, the reviewers specifically included the 17 studies reporting on acute CCD-related events (odds ratio 1.357). Moreover, four studies evaluating CCD-related deaths showed a higher risk in HCV patients than controls (odds ratio 1.772).
Meta-regression models suggested a direct association between the prevalence of cirrhosis and difference in CCD risk between HCV patients and controls.
The risk of coronary artery disease and cerebrovascular disease in patients with hepatitis C: A systematic review and meta-analysis. Ambrosino P, Lupoli R, Di Minno A et al. Int J Cardiol. 2016 Jul 4; 221:746-754 [Epub ahead of print]
Sofosbuvir-based regimens successful in lung transplant HCV patients
Three HCV patients who underwent lung transplant have been safely treated with IFN-free sofosbuvir-based regimens.
They all received anti-HCV treatment after lung transplant with sofosbuvir-based regimens, and all achieved a SVR. No unexpected safety signals were observed and no modifications in immunosuppressants were required.
The authors of the case report, from the University of Milan, also carried out a literature review and found no other data on the safety and efficacy of IFN-free regimens in HCV patients who received lung transplants.
They suggested that their case report opens the door for refined clinical management of this category of patients.
Sofosbuvir-based regimens for the treatment of HCV in patients who underwent lung transplant: case series and review of the literature. D'Ambrosio R, Aghemo A, Rossetti V et al. Liver Int. 2016 Jul 18 [Epub ahead of print]
NAs after HBIG protect against HBV/HDV recurrence following transplant
After HB immunoglobulin (HBIG) was ended in liver transplant (LT) patients with HBV/HDV coinfection, maintenance therapy with nucleos(t)ide analogue(s) (NAs) prevented its recurrence.
In a study at Greece’s Medical School of Aristotle University, 34 patients transplanted for HBV/HDV cirrhosis were evaluated. After LT, each patient received HBIG + NAs and then continued with NAs prophylaxis. All patients were followed up with HBV serum markers and HBV DNA, while anti-HDV/HDV RNA was performed in those with HBV recurrence. After HBIG discontinuation, the NAs were received as monoprophylaxis (lamivudine, adefovir, entecavir or tenofovir; or dual prophylaxis (lamivudine plus adefovir or tenofovir)).
Two of the 34 patients had HBV/HDV recurrence after HBIG withdrawal at a median follow-up of 28 months. These two patients had undetectable HBV DNA at LT. Statistical analysis revealed those with recurrence had received HBIG for shorter periods, compared to those without recurrence (median nine months versus 28 months).
Nucleos(t)ide analogue(s) prophylaxis after hepatitis B immunoglobulin withdrawal against hepatitis B and D recurrence after liver transplantation. Cholongitas E, Goulis I, Antoniadis N et al. Transpl Infect Dis. 2016 Jul 15 [Epub ahead of print]
DAAs safe and effective in chronic HCV with cirrhosis
A large real world study has shown direct-acting antiviral (DAA)-based therapy is safe and effective in HCV patients with compensated Child-Pugh score (CP) A cirrhosis.
In this multi-national study, at centres in Canada, Germany and the Netherlands, 433 cirrhotic patients with chronic HCV infection started DAA-based treatment.
The SVR12 rate was similar among patients with CP A (85.9%) and CP B/C (82.2%). Baseline albumin <35 g/L (hazard ratio 3.11), baseline MELD score ≥14 (hazard ratio 1.63) and HCV genotype 3 (hazard ratio 2.05) were independently associated with hepatic decompensation during antiviral treatment among patients with CP B/C.
The researchers suggest that, for patients with decompensated (CP B/C) cirrhosis, albumin <35 g/L, MELD-score ≥14 and HCV genotype 3 are important risk factors for hepatic decompensation during DAA-based treatment. Therefore, these patients require close monitoring during antiviral therapy or treatment should be deferred until after transplantation.
Safety and effectiveness of DAA-based therapy in patients with chronic HCV infection and cirrhosis. Maan R, van Tilborg M, Deterding K et al. Clin Gastroenterol Hepatol. 2016 Jul 9 [Epub ahead of print]
Low HEV transfusion transmission risk from blood donors
Although HEV transfusion transmitted infection (TTI) has been reported in some European countries, a large Danish study found no evidence of it in blood donations.
In the study, by researchers from four university hospitals, samples from 25,637 consenting donors collected during one month in 2015 were screened retrospectively using an individual-donation HEV RNA nucleic acid test with a 95% detection probability of 7.9 IU/mL.
Eleven donations (0.04%) were confirmed as positive for HEV RNA (median HEV RNA level, 13 IU/mL). Two donations were successfully genotyped as HEV-gt-3. Only one donor had a travel history outside Europe. Nine of eleven donors were male, but the gender ratio was non-significant compared with the total donor population.
Seven available recipients tested negative for HEV RNA and anti-HEV immunoglobulin M in follow-up samples. One recipient was HEV RNA-negative but anti-HEV immunoglobulin G-positive. HEV TTI was considered unlikely, but a transfusion-induced secondary immune response could not be excluded. Phylogenetic analysis showed relatively large sequence differences between HEV from donors, symptomatic patients, and swine.
The researchers concluded that despite an HEV RNA prevalence of 0.04% in Danish blood donations, all HEV-positive donations carried low viral loads, and no evidence of TTI was found.
Low transfusion transmission of hepatitis E among 25,637 single-donation, nucleic acid-tested blood donors. Harritshøj LH, Holm DK, Saekmose SG et al. Transfusion. 2016 Jul 7 [Epub ahead of print]
Global burden of viral hepatitis increased over 23 years
New global data show the absolute burden and relative rank of viral hepatitis has increased over the past quarter of a century.
A multi-national team of researchers used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013.
Global viral hepatitis deaths increased in that period, from 0.89m to 1.45m, and the sum of years lost went from 31m to 41.6m and years lived with disability from 0.65m to 0.87m. Disability-adjusted life-years increased from 31.7m to 42.5m. In 2013, viral hepatitis was the seventh leading cause of death worldwide, compared with tenth in 1990.
The researchers concluded that, unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. They suggest the enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, represents an important opportunity to improve public health.
The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013. Stanaway JD, Flaxman AD, Naghavi M et al. Lancet. 2016 Jul 6 [Epub ahead of print]
People with HCV take more risks than those with other liver diseases
People with HCV appear to be more impulsive and take more risks than individuals with other liver diseases, a new study suggests.
In the study, at Brazil’s Federal University of Bahia, Brazil, 269 adults with liver diseases were divided into a viral group of 157 patients with HCV and a non-viral group of 112. Risk behaviours were evaluated by a socio-demographic questionnaire. Impulsivity was assessed through Barratt Impulsiveness Scale (BIS-11). Psychiatric comorbidities were investigated by the Mini International Neuropsychiatric Interview 5.0.0.
The viral group patients had higher impulsivity than the non-viral group in all domains: attentional impulsivity, motor impulsivity, and non-planning. Risk behaviours were also shown to be associated with impulsivity levels. The results suggest that HCV-infected patients are more impulsive than individuals with other liver diseases, even when analyses are controlled for the presence of comorbid mental disorders. In addition, at-risk behavior was significantly mediated by impulsivity.
Risk-taking behavior and impulsivity among HCV-infected patients. Dantas-Duarte A, Morais-de-Jesus M, Nunes AP et al. Psychiatry Res. 2016 Jun 22; 243:75-80 [Epub ahead of print]
Collaborative care improves depression in HCV clinics
Collaborative care modestly improved depression among patients treated at chronic HCV clinics, a new study found
Collaborative care models have been shown to improve depression outcomes in primary care settings. The new study was conducted at four chronic HCV clinics in US Veterans Affairs facilities by a collaborative depression care team consisting of a depression care manager, pharmacist and psychiatrist.
Baseline screening identified 263 HCV-infected patients with depression. In unadjusted analyses, intervention participants' reports trended toward more treatment response (19% versus 13%) and remission (12% versus 6%), but total number of depression-free days (50.9) was similar to that of usual care participants (50.7).
These trends did not reach statistical significance for the overall sample in the adjusted analyses: response (odds ratio 2.02), remission (odds ratio 2.63), and depression-free days (7.6). However, the intervention was effective in improving all three outcomes for patients who did not meet criteria for remission at baseline.
Collaborative care for depression in chronic hepatitis C clinics. Kanwal F, Pyne JM, Tavakoli-Tabasi S et al. Psychiatr Serv. 2016 Jul 1 [Epub ahead of print]
HBV non-immunity in liver transplant children is higher than expected
A new article reviews the significance of HBV infection and the vaccination and screening measures needed to achieve immunity in children receiving liver transplants.
The review found HBV non-immunity among transplant candidates is higher than expected, even after appropriate completion of the vaccine series. Annual measurement of quantifiable HBV surface antibody in this vulnerable group should guide administration of booster and/or re-vaccination, thus improving immunoprotection.
The authors point out the liver plays a vital role in immune regulation. It induces immune tolerance and competence, and both clears antigens from the circulation and generates liver-primed memory cells through antigen presentation via hepatic scavenger cells. Lymphocyte populations are depleted in patients with liver disease.
The reviewers summarise immunity provided during early childhood against HBV infection is important to both paediatric liver transplant candidates and aging recipients. The field of paediatric transplantation is ripe for further functional cellular and humoral immunity studies on childhood HBV vaccines.
Hepatitis B immunity in the pediatric liver transplant population. Patel SS, Leung DH. Curr Opin Pediatr. 2016 Jun 29 [Epub ahead of print]
HCV treatment adherence does not affect liver transplant risk
This observational, historical cohort study was conducted using administrative data from the [US] Humana Research Database amongst 43,046 appropriate HCV patients diagnosed between 2008, and 2013. Cox proportional hazards models were used to estimate the relative risk of liver transplant by level of treatment adherence (> 80%, 50%-79%, and < 50%) based on proportion of days covered.
Only 2,708 (6.29%) of the patients received HCV treatment, and 366 (<1%) received a liver transplant. Although there were no significant differences in the risk of liver transplant by adherence level, there was an upwards trend in the rate of liver transplant as adherence worsened (> 80%: 1.25%; 50%-79%: 1.30%; and <50%:1.99%), and the average days to liver transplant was longer with higher adherence (> 80%: 683; 50%-79%: 623; < 50%: 454). Only 48 (13.11%) patients who received a liver transplant were treated for HCV.
Adjusted median total and per patient per month health care costs measured from index date until end of the study period were significantly higher for patients who received HCV treatment compared with those who did not (US$231,139 versus US$86,167, and US$20,583 versus US$5,778, respectively), driven by HCV-related medical costs and total pharmacy costs.
Does hepatitis C treatment adherence affect risk of liver transplantation? A historical cohort study. Ems D, Racsa P, Anderson C et al. J Manag Care Spec Pharm. 2016 Jul;22(7):863-71
Few treatment failures with oral HCVs in routine practice
A total of 363 chronic HCV patients treated outside clinical trials with all-oral DAA regimens at three hepatitis clinics in Spain were retrospectively examined. Host and viral factors were tested as predictors of treatment failure.
All but 14 (4%) patients achieved sustained virological responses. Ten failures occurred after 12 weeks of sofosbuvir-ledipasvir, despite five of them being on ribavirin. All failures but one were relapses. The only patient with viral breakthrough selected NS5B L159F and NS5A Y93H.
In multivariate analyses, only advanced liver fibrosis and HIV coinfection were significantly associated with treatment failure. A trend towards a lower response was seen for HCV genotype 4.
Rate and predictors of treatment failure to all-oral HCV regimens outside clinical trials. Arias A, Aguilera A, Soriano V et al. Antivir Ther. 2016 Jun 24 [Epub ahead of print]
HBV or HCV may increase risk of non-Hodgkin lymphoma
This case-control multicentre study in Italy enrolled 571 NHL patients and 1004 cancer-free matched controls.
Circulating HCV RNA was detected in 63 NHL cases and 35 controls (odds ratio 3.51). Chronic HBV infection was found in 3.7% of cases and 1.7% of controls (odds ratio 1.95). There was a significantly elevated odds ratio for B-cell NHL (odds ratio 2.11).
People with serological evidence of past HCV or HBV infection, vaccination against HBV, or detectable antibodies against HBV core antigen alone were not at increased NHL risk.
The researchers suggest that the prevention and treatment of HCV and HBV may diminish the NHL incidence, notably in areas with a high prevalence of hepatitis virus infection.
Hepatitis B and C viruses and risk of non-Hodgkin lymphoma: a case-control study in Italy. Taborelli M, Polesel J, Montella M et al. Infect Agent Cancer. 2016 Jun 23; 11: 27
Longer sleep length may increase NAFLD risk
New evidence suggests that sleeping for a longer time at night may slightly increase the risk of non-alcoholic fatty liver disease (NAFLD) in middle-aged and elderly people.
A total of 8,965 NAFLD-free subjects with a mean age of 61.6 who had enrolled in the Chinese Dongfeng-Tongji cohort study at baseline were divided into five groups dependent on their sleep duration: under six hours, six to seven hours, seven to eight hours, eight to nine hours, and nine hours or more.
During five years of follow-up, 2,197 participants were newly diagnosed as NAFLD. Compared with those reported seven to eight hours of night-time sleep, the multivariable-adjusted odds ratios were 1.21 for those who slept eight to night hours and 1.31 for those who slept over nine hours. However, no significant association was found with short nightly sleep duration, i.e., under seven hours.
The effect of long night-time sleep on the risk of incident NAFLD was attenuated greatly by body mass index in men.
Night-time sleep duration and risk of nonalcoholic fatty liver disease: the Dongfeng-Tongji prospective study. Liu C, Zhong R, Lou J et al. Ann Med. 2016 Jun 21:1-9. [Epub ahead of print]
Better liver transplant outcomes with rabbit antithymocyte globulin
People who received rabbit antithymocyte globulin induction before liver transplantation had lower rejection rates and improved patient and graft survival than those receiving interleukin 2 receptor blocker.
This was the finding of a retrospective analyses using the University of Washington [Seattle] Transplant Database from 2005 to 2012 for adult primary liver transplant patients. Maintenance immunosuppressive agents were tacrolimus or tacrolimus-mycophenolate mofetil. Among 595 patients, 322 received rabbit antithymocyte globulin and 273 received interleukin 2 receptor blocker.
Acute cellular rejection was higher in those who received interleukin 2 receptor blocker than in those who received rabbit antithymocyte globulin (27% versus 18%).
Both patient survival at one year (95% versus 90%), three years (92% versus 87%), and five years (86% versus 80%) and graft survival at one year (93% versus 88%), three years (90% versus 86%), and five years (83% versus 78%) were superior with rabbit antithymocyte globulin than with the interleukin 2 receptor blocker.
In patients with HCV, the type of induction therapy did not have any effect on the timing of HCV recurrence. At one year after transplant, 33.3% in the rabbit antithymocyte globulin group had grade three to four inflammation and 10.2% had stage three to four fibrosis, compared with 16.8% and 4.8% in the interleukin 2 receptor blocker group.
Female recipient, Model for End-Stage Liver Disease score, hepatocellular carcinoma, and high preoperative serum creatinine levels were associated with less favourable patient and graft survival.
Superior patient and graft survival in adult liver transplant with rabbit antithymocyte globulin induction: experience with 595 patients. Montenovo MI, Jalikis FG, Li M et al. Exp Clin Transplant. 2016 Jun 15 [Epub ahead of print]
Warning on neurologic complications in liver disease
Several drugs used to treat liver disease, including classic and new direct-acting antivirals, may have neurologic complications.
This was the final conclusion of a review by neurologists from the University of Lisbon, who point out that type A hepatic encephalopathy (HE), which occurs in acute liver failure, is a neurologic emergency. They also said multiple measures should be taken to prevent and treat cerebral oedema.
In Type C HE, which occurs in chronic liver disease, management should be aimed at correcting precipitant factors and hyperammonemia. There is an increasing spectrum of drug treatments available to minimize ammonia toxicity.
Acquired hepatocerebral degeneration is a rare complication of the chronic form of HE, with typical clinical and brain MRI findings, whose most effective treatment is liver transplantation. Epilepsy is frequent and of multifactorial cause in patients with hepatic disease, and careful considerations should be made regarding choice of the appropriate anti-epileptic drugs.
Several mechanisms increase the risk of stroke in hepatic disease, but many of the drugs used to treat and prevent stroke are contraindicated in severe hepatic failure.
HCV increases the risk of ischemic stroke. Hemorrhagic stroke is more frequent in patients with liver disease of alcoholic etiology. Viral hepatitis is associated with a wide range of immune-mediated complications, mostly in the peripheral nervous system, which respond to different types of immunomodulatory treatment.
Management of neurologic manifestations in patients with liver disease. Ferro JM, Viana P, Santos P et al. Curr Treat Options Neurol. 2016 Aug;18(8):37
Chronic liver disease increases risks after cervical spine trauma
Chronic liver disease patients who have suffered cervical spine trauma may have an increased risk of morbidity and mortality.
This was the novel finding by researchers at Brigham and Women's Hospital, Boston, who analysed patient records in the Massachusetts Statewide Inpatient Dataset (2003-2010).
Among 10,841 patients with cervical spine trauma, 117 had chronic liver disease. The rate of surgical intervention for cervical trauma was not significantly different between patients with and without chronic liver disease (odds ratio 0.82).
Mortality (odds ratio 2.12), failure to rescue (odds ratio 2.86), and complications (odds ratio 1.65) were all significantly increased for the patients with chronic liver disease in final adjusted models that controlled for differences in case-mix and whether a surgical procedure was performed. Final models explained approximately 72% of the variation in mortality and failure to rescue.
The effect of chronic liver disease on acute outcomes following cervical spine trauma. Bessey JT, Le H, Leonard DA et al. Spine J. 2016 Jun 8 [Epub ahead of print]
Risk factors for HCC include liver fibrosis, steatosis, diabetes and cirrhosis
Two new studies suggest risk factors for hepatocellular carcinoma (HCC) in hepatitis patients include liver fibrosis, steatosis, diabetes and cirrhosis.
Japanese researchers cited liver fibrosis and steatosis as risk factors, regardless of past HBV infection and alcohol consumption (1).
Among HCC patients who underwent surgical resection at Shinshu University Hospital, Japan, between 1996 and 2012, 77 were negative for serum anti-HBV core/surface antibodies in addition to HBV surface antigen and anti-HCV antibody.
Advanced fibrosis and steatosis were detected in 64% and 60% of all patients. Approximately 85% of alcohol intake-positive patients had advanced fibrosis. Non-alcoholic fatty liver patients had the highest body mass index and prevalence of diabetes, but between 30% and 40% had none-to-mild fibrosis.
Cryptogenic patients (i.e., no alcohol intake or steatosis) exhibited the lowest incidence of accompanying hepatic inflammation/fibrosis but the largest tumour size. Recurrence/survival rates were comparable among the groups.
Meanwhile, Swedish researchers cited diabetes and cirrhosis as strong risk factors following successful treatment of HCV (2).
Among 399 patients with advanced liver disease successfully treated for HCV at Karolinska University Hospital, 17 developed HCC during 3366 person-years follow-up. The HCC incidence rates were 0.95 and 0.15 per 100 person years for patients with pre-treatment METAVIR F4 and F3, respectively.
Patients with pre-treatment cirrhosis and diabetes had a hazard ratio to develop HCC of 6.3, and an incidence rate of 7.9/100 person-years during the first two years of follow-up. The risk for HCC decreased significantly two years after SVR had been achieved.
1. Clinicopathological characteristics of non-B non-C hepatocellular carcinoma without past HBV infection. Kimura T, Kobayashi A, Tanaka N et al. Hepatol Res. 2016 Jun 11 [Epub ahead of print]
2. Diabetes and cirrhosis are risk factors for hepatocellular carcinoma after successful treatment of chronic hepatitis C. Hedenstierna M, Nangarhari A, Weiland O et al. Clin Infect Dis. 2016 Jun 9 [Epub ahead of print]
Sofosbuvir plus daclatasvir “best option” for HCV g3
A literature review concluded the sofosbuvir (SOF) and daclatasvir (DCV) combination is the best oral therapy for HCV genotype three.
Moreover, the addition of ribavirin (RBV) does not appear to increase SVR rates substantially.
Authors from the University of Seville reviewed the therapeutic efficacy of various treatment regimens in HCV genotype three from randomised clinical trials and prospective National Cohort Studies. The options included PEG-INF-based therapy including SOF + RBV for 12 weeks versus SOF + RBV for 24 weeks; SOF + RBV therapy 12-16 weeks versus 24 weeks; and the role of RBV in SOF + daclatasvir (DCV) and SOF + ledipasvir (LDV) combinations.
The analysis found a combination treatment including SOF + RBV + PEG-IFN for 12 weeks produced a better SVR than SOF + RBV only for 12 weeks, although its association with more frequent adverse effects may be a limiting factor.
Longer duration therapy with SOF + RBV (24 weeks) has achieved higher SVR rates than shorter durations (12 or 16 weeks). The review suggests that SOF + LDV is not an ideal treatment for genotype three.
Hepatitis C virus genotype 3: Meta-analysis on sustained virologic response rates with currently available treatment options. Ampuero J, Reddy KR, Romero-Gomez M. World J Gastroenterol. 2016 Jun 14;22(22):5285-92
HBV a risk factor for periprosthetic joint infection after TKA in men
HBV infection is a risk factor for periprosthetic joint infection (PJI) among males after total knee arthroplasty (TKA), a new study shows.
Researchers studied 4,619 patients (1184 male) undergoing primary TKA in Taiwan between 2001 and 2010. The incidence of PJI was 523 among the males with HBV infection and 110 among the males without HBV (per 10,000 person-years). The males with HBV infection had a 4.32-fold risk of PJI compared with the males without HBV. HBV infection and diabetes were the risk factors for PJI among males.
The incidence of PJI was 58.8 among the females with HBV infection and 75.2 among the females without HBV (per 10,000 person-years). The risk of PJI was higher for the males with HBV infection than for the males without 0.5 to one year after TKA (hazard ratio 18.7) and over one year after TKA (hazard ratio 4.80).
Hepatitis B virus infection is a risk factor for periprosthetic joint infection among males after total knee arthroplasty: a Taiwanese nationwide population-based study. Kuo SJ, Huang PH, Chang CC et al. Medicine (Baltimore). 2016 May; 95(22): e3806
Experts disagree on timing of HBV vaccination for young children
Researchers say a French survey suggesting children can wait until they are 11 years old before being vaccinated for HBV is unacceptable and potentially damaging.
The objective of the survey (1), conducted at the University of Lille, was to identify potentially dangerous vaccination delays for each dose of ten different vaccines in children younger than two years.
Sixteen experts in vaccines for children responded from the Infovac-France group and 21 responded from the French study group for pediatric infectious diseases. They identified maximum delays for all vaccine doses.
The group reached a 70% cut-off consensus for six of the 10 vaccines. They agreed delays of 15 days after the recommended date for the first two doses of the diphtheria-tetanus-acellular pertussis-inactivated polio vaccine/Haemophilus influenzae B vaccine and for the second dose of the pneumococcal conjugate vaccine, one month for the meningococcal C vaccine and for the first dose of the measles-mumps-rubella vaccine, and 11 years of age for completion of the HBV vaccination.
However, in the following issue of the same journal (2), experts from Belgium, France, Greece and the USA point out that control of HBV through routine infant immunization in more than 95% of countries has reduced chronic hepatitis carriers to less than 1%-2% in immunized cohorts of children even in countries where it is endemic.
They write: “large cohorts of French children and adolescents remain susceptible to HBV infection. Given the high rates of immigration to France from areas of higher endemicity, the higher birth rate and degree of integration of these groups into the health system, plus the lower age of sexual debut and the use of injectable drugs in the general population, we cannot agree that a delay of 11 years is acceptable. Rates of adolescent immunization are quite low so relying on protection at this age will yield little in terms of population protection”.
They add that allegations persisted in France that the HBV vaccine caused Multiple Sclerosis and conclude “the results of this paper sends a damaging message to health workers and parents in France and beyond”.
1.What timing of vaccination is potentially dangerous for children younger than 2 years? Gras P, Bailly AC, Lagrée M et al. Hum Vaccin Immunother. 2016 May 24:1-7 [Epub ahead of print]
2.Global progress in the control of viral hepatitis and acceptable delay in Hepatitis B immunization. Kane MA, Roudot-Thoraval F, Guerin N et al. Hum Vaccin Immunother. 2016 Jun 3:1-4 [Epub ahead of print]
More cirrhosis, worse outcomes, for patients with both AIH and NASH
Patients with both autoimmune hepatitis (AIH) and nonalcoholic steatohepatitis (NASH) are more likely to have cirrhosis and decreased survival compared to AIH-only patients, researchers reported.
The researchers, at the University of Vermont Medical Centre, studied 73 AIH patients; 14% were classified as AIH with simple steatosis (SS) and 16% had AIH and NASH.
Fifty percent of the AIH plus NASH patients had cirrhosis at index biopsy as compared to 18% of AIH-only patients. AIH/NASH patients had relative risks of 7.65 for liver-related mortality and 2.55 for liver-related adverse outcomes, as compared to the AIH-only cohort. No significant difference in outcome measures existed in comparing (AIH only) with (AIH and SS) cohorts.
The researchers say their findings suggest that simultaneous exposure confers a clinically significant increased risk, which may warrant closer follow-up and surveillance.
Natural history of patients presenting with autoimmune hepatitis and coincident nonalcoholic fatty liver disease. De Luca-Johnson J, Wangensteen KJ, Hanson J et al. Dig Dis Sci. 2016 Jun 4. [Epub ahead of print]
Multi-disciplinary approach improves HCV outcomes
A study at a Spanish hospital found that the multi-disciplinary management of chronic HCV improved outcomes in patients.
Researchers at the Hospital de Sabadell, Barcelona, compared 228 HCV patients treated with pegylated interferon plus ribavirin before the implementation of a multidisciplinary approach with 286 treated after the implementation of the approach.
Age, viral genotype, previous treatment, aspartate transaminase, ferritin, and triglyceride were prognostic factors of a sustained virological response. After adjusting for prognostic factors, a sustained virological response was higher in the multidisciplinary cohort (58% versus 48%).
Despite a higher psychiatric co-morbidity and age in the multidisciplinary cohort, there was a trend toward a lower rate of treatment abandonment in this group (2.2% versus 4.9%).
Effects of a multidisciplinary approach on the effectiveness of antiviral treatment for chronic hepatitis C. Gallach M, Vergara M, Miquel M et al. Ann Hepatol. 2016 Jul-Aug;15(4):524-31
Chinese herbs improve interferon/ribavirin therapy in chronic HCV
A meta-analysis of clinical studies suggests adding a combination of Chinese herbs to interferon and ribavirin yields better outcomes, and fewer adverse events, in chronic HCV than interferon plus ribavirin alone.
Researchers at the International Centre for Diagnosis and Treatment of Liver Diseases in Beijing found 17 randomised controlled trials that evaluated biochemical responses, virological responses, histological responses, and/or adverse reactions to combination therapy of interferon and ribavirin with and without Chinese herbs.
Overall, combination therapies with Chinese herbs plus interferon and ribavirin achieved significantly higher alanine transaminase and end-of-treatment viral response, and significantly lower levels of hyaluronic acid, laminin, procollagen iii peptide, type IV collagen, decreased leukocyte count, abnormal thyroid function, psychosis, and anaemia in chronic HCV patients compared with those treated without Chinese herbs. Sensitivity analysis showed no changes and no potential publication bias was found.
Meta-analysis of combination therapy of Chinese herbs plus interferon and ribavirin in patients with chronic hepatitis C. Wang J, Xin S, Jin X et al. Med Sci Monit. 2016 May 30; 22:1817-1826
Inner-city prescription opioid injectors at greater risk of HCV
People who inject prescription opioids and who live in inner-city areas have a higher risk of HCV than those in the suburbs, a new Canadian study suggests.
The study researchers interviewed 854 people who inject drugs and who lived in the inner-city of Montreal or in the surrounding areas, every three to six months from 2004 to 2012. At baseline, 40% of inner-city participants were more likely to report prescription opioid injecting in the past month compared with 25% of suburban residents.
The association between prescription opioid injection and heroin injection, syringe sharing and sharing of injecting equipment varied according to place of residence and was greater in the inner city.
The hazard of HCV infection associated with prescription opioid injection was greater among inner-city participants compared to those in the surrounding areas (adjusted hazard ratios 3.19 versus 1.26).
The role of living context in prescription opioid injection and the associated risk of hepatitis C infection. Sacks-Davis R, Daniel M, Roy E et al. Addiction. 2016 May 30 [Epub ahead of print]
Simtuzumab well tolerated in HCV/HIV advanced liver fibrosis
Simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2 enzyme, has been shown to be well-tolerated in HCV- and HIV-infected subjects with advanced liver disease.
In an open-label, pilot multi-centre clinical trial, 18 patients with HCV, HIV or HCV-HIV co-infection and advanced liver fibrosis received simtuzumab 700mg intravenously every two weeks for 22 weeks. Transjugular liver biopsies were performed during screening and at the end of treatment to measure hepatic venous pressure gradient (HVPG) and to stage fibrosis.
The treatment was well-tolerated with no discontinuations because of adverse events. No significant changes were seen in HVPG or liver biopsy fibrosis score after treatment. Exploratory transcriptional and protein profiling using paired pre- and post-treatment liver biopsy and serum samples suggested up-regulation of TGF-β3 and IL-10 pathways with treatment.
The researchers suggest that putative modulation of TGF-β3 and IL-10 pathways during simtuzumab treatment merits investigation in future trials.
Simtuzumab treatment of advanced liver fibrosis in HIV and HCV-infected adults: results of a 6-month open-label safety trial. Meissner EG, McLaughlin M, Matthews L et al. Liver Int. 2016 May 27 [Epub ahead of print]
Clinicians wary of HCV treatment for people who inject drugs
A new survey has found a low rate of prescribing amongst physicians when treating HCV patients who inject drugs.
Researcher at the University of California, San Francisco surveyed clinicians attending the Liver Meeting in 2014 who reported prescribing HCV treatment in the past three years.
Among 108 clinicians completing the survey, 10% were willing to treat a person who injected drugs (last injection within 30 days) using interferon-containing regimens, and 15% with all-oral regimens.
For each increasing time interval of injection abstinence, there was an increase in the odds of a clinician reporting willingness to treat with direct-acting antivirals (odds ratio 2.57) and with interferon-based treatment (odds ratio 2.22), Reinfection and medication cost were cited as most important concerns when determining candidacy.
The researchers concluded that a cure is now the norm in HCV treatment, and that there is an increasing need to address the barriers to treating people who inject drugs, the population with the highest burden of infection. Understanding treatment candidacy assessments is essential to improving uptake.
Clinicians' views of Hepatitis C Virus treatment candidacy with direct-acting antiviral regimens for people who inject drugs. Asher AK, Portillo CJ, Cooper BA et al. Subst Use Misuse. 2016 May 24:1-6 [Epub ahead of print]
Renal impairment common in HCV patients
Some degree of renal impairment is common in people with HCV, including those with advanced liver fibrosis, researchers have found.
In a population-based prospective, observational cohort study at four large US health systems, data on 5,772 HCV patients was analysed.
The prevalence of estimated glomerular filtration rate (eGFR) = 80 was 33% and eGFR < 30 was 2%, including among patients with hepatic fibrosis. Diagnosed extra hepatic renal manifestations were rare: vasculitis- 0.2%, nephrotic syndrome- 0.3%, and cryoglobulinemia- 0.9%.
The researchers concluded that, while the prevalence of severe renal impairment was low, mild-to-moderate renal impairment was common in HCV patients, including those with advanced liver fibrosis for whom treatment is urgent.
Prevalence of renal Impairment and associated conditions among HCV-infected persons in the Chronic Hepatitis Cohort Study (CHeCS). Moorman AC, Tong
Single-tablet multi-drug regimen effective in HIV/HBV co-infection
A tablet containing elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide (E/C/F/TAF) was effective in HIV/HBV co-infected adults, a new study showed.
In this US multi-centre, open-label, non-comparative switch study, at week 48, 91.7% of the 72 participants maintained or achieved virologic suppression (HIV-1 RNA <50 c/mL; HBV DNA <29 IU/mL.)
Seroconversion occurred in 2.9% of HBsAg positive participants and 3.3% of HBeAg positive participants; 40% of those with abnormal ALT normalized. E/C/F/TAF was associated with improved renal function and reduced bone turnover.
Efficacy and safety of switching to a single-tablet regimen of elvitegravir/cobicistat/emtricitabine/tenofovir Aaafenamide (E/C/F/TAF) in HIV-1/Hepatitis B coinfected adults. Gallant J, Brunetta J, Crofoot G et al. J Acquir Immune Defic Syndr. 2016 May 11 [Epub ahead of print]
Chronic HBV infection may lessen risk of pre-eclampsia
Findings from a meta-analysis of published studies suggest chronic HBV may decrease the risk of pre-eclampsia.
The reviewers found three observational cohort studies and eight case-control studies, including 11,566 preeclampsia patients, conducted up to 1 January 2016 in Asian populations. A significant negative association between chronic HBV infection and pre-eclampsia was observed (odds ratio 0.77).
The reviewers suggest future prospective cohorts in different countries with larger sample sizes are warranted to ascertain the causality. Pathophysiological studies are required to explore the possible biological mechanisms involved, they added.
Chronic hepatitis B infection is associated with decreased risk of preeclampsia: a meta-analysis of observational studies. Huang QT, Chen JH, Zhong M et al. Cell Physiol Biochem. 2016 May 9;38(5):1860-1868 [Epub ahead of print]
HBV infection “possible” following haemodialysis
HBV infection is possible following hemodialysis, especially among severely immunosuppressed patients.
Following an investigation of a report made in March 2013, US public health authorities, from the Epidemic Intelligence Service, have warned of this possibility, and recommended stringent infection control.
They found that the patient's only identified HBV risk factor was hemodialysis treatment, and that the facility had no other patients with known active HBV infection.
An investigation of one patient with evidence of a resolved HBV infection indicated HBV reverse seroconversion and reactivation had occurred in the setting of HIV infection and a failed kidney transplant.
HBV whole genome sequences analysis from the index and source patients indicated 99.9% genetic homology. Facility observations revealed multiple infection control breaches. Inadequate dilution of the source patient's sample during HBV testing might have led to a false-negative result, delaying initiation of hemodialysis in isolation.
Hepatitis B reverse seroconversion and transmission in a haemodialysis centre: a public health investigation and case report. Rhea S, Moorman A, Pace R et al. Am J Kidney Dis. 2016 May 7 [Epub ahead of print]
Managing HCV drug treatment failure
Although in HCV studies, SVRs above 90% have been achieved with direct-acting antiviral (DAA) combinations, outcomes in real-world patients are lower. In a review, authors from Spain and the UK have discussed the management of HCV treatment failure and the impact of resistance-associated variants (RAVs) on re-treatment strategies.
The authors say that failure to DAA combinations occurs more often in chronic HCV patients with baseline predictors of poor response, such as those with RAVs, genotypes 3 or 1a, advanced liver cirrhosis, elevated serum HCV-RNA and perhaps HIV coinfection. Impaired antiviral efficacy is more frequent when multiple factors are present.
On-treatment predictors of DAA failure are poor drug adherence and development of side effects. Extending the length of therapy, adding ribavirin and/or using DAA from other drug families may allow successful re-treatment of most prior DAA failures.
Prevention and management of treatment failure to new oral hepatitis C drugs. Benítez-Gutiérz L, Barreiro P, Labarga P et al. Expert Opin Pharmacother. 2016 May 5. [Epub ahead of print]
Muscle weakness associated with hepatic encephalopathy in cirrhosis
Findings from a new study suggest a significant relationship between skeletal muscle weakness and neurological impairment in cirrhotic patients.
This cross-sectional multi-centre study in Brazil included 54 cirrhotic outpatients with hepatic encephalopathy (HE) varying from subclinical to grade II, who were submitted to neuropsychometric tests, electroencephalogram, brain Single Photon Emission Computed Tomograph, anthropometric measurements, handgrip strength and dual energy X-ray absorptiometry exam.
Analysis of the area under the receiver operator characteristic curve revealed the values related to neurological manifestations (HE grades I and II). Reductions in adductor pollicis muscle thickness and hand grip strength were associated with higher HE grades, suggesting a big impact caused by the loss of muscle mass and function on HE severity.
Lower values of handgrip strength and adductor pollicis muscle thickness are associated with hepatic encephalopathy manifestations in cirrhotic patients. Augusti L, Franzoni LC, Santos LA et al. Metab Brain Dis. 2016 Apr 30. [Epub ahead of print]
Race and gender differences in the use of anti-HCV drugs
New evidence from the USA has found “unexplained” race and gender differences in the use of new direct acting antiviral agents (DAAs) amongst people with HCV.
Researchers at Baylor College of Medicine, Houston, studied HCV patients who received care at Veterans Administration facilities nationwide. Those who were treated in the current DAA era were compared with those who were seen in the previous standard of care era.
Of the 145,596 patients seen in the current DAA era, 17,791 received treatment during the first 16 months of DAA approval. African American
(AA) patients had 21% lower odds of receiving DAA than whites (odds ratio 0.79). Overall, women were as likely to receive treatment as men (odds ratio 0.99). However, the odds of receiving DAAs were 29% lower for younger women compared with younger men (odds ratio 0.71).
In the previous era, similar to the DAA cohort, AA patients had significantly lower odds of receiving treatment than whites (odds ratio 0.74). The racial difference between the two eras did not reach statistical significance.
The researchers described their findings as “unexplained”
Race and gender differences in the use of direct acting antiviral agents for HCV. Kanwal F, Kramer JR, El-Serag HB et al. Clin Infect Dis. 2016 Apr 30 [Epub ahead of print]
Myrcludex B - an effective novel HBV/HDV treatment
Myrcludex B is a new drug to treat HBV and HDV. In a multi-centre German first-in-human study (1), single ascending doses of myrcludex B were administered up to 20 mg intravenously and 10 mg subcutaneously in 36 healthy volunteers.
Myrcludex B was well tolerated and no serious or relevant adverse events representing off-target effects, and no immunogenic effects were observed up to the highest applied dose. The pharmacokinetic model suggested that subcutaneous doses of 10 mg and above reach a target saturation of over 80% for at least 15 hours.
In a pilot trial conducted at centres in Russia and Germany, 24 patients with chronic HDV were equally randomized to myrcludex B, or pegylated interferon alpha (pegIFNα-2a) or their combination (2).
Interim results showed that, after 24 weeks of treatment, HDV RNA, a relevant marker for HDV infection, decreased in all patients. Two of eight patients who received either myrcludex B or pegINF2a became negative for HDV RNA, and five of seven patients who received both drugs at the same time became negative. The drug was well tolerated.
1. Myrcludex B: a first-in-human clinical study with a first-in-class hepatitis B and hepatitis D virus entry inhibitor. Blank A, Markert C, Hohmann N et al. J Hepatol. 2016 Apr 27 [Epub ahead of print]
2. Interim results of a Phase Ib/IIa study of the entry inhibitor myrcludex B in chronic hepatitis D infected patients. Bogomolov P, Alexandrov A, Voronkova N et al. J Hepatol. 2016 Apr 27 [Epub ahead of print]
Stool could be a source of HCV infection
A new German study shows, for the first time, that HCV can often be detected in stool samples of chronically infected patients irrespective of occult bleeding. This, say the study authors, suggests that stool could be a potential source for HCV infection.
Researchers at Hannover Medical School retrospectively collected stool samples of 98 HCV patients. Specific HCV primers were used to identify samples positive for HCV RNA. HCV RNA-positive samples were tested for HCVcoreAg with the Architect HCVAg assay. Presence of occult blood was investigated by the hemoCARE guajak test. Viral stability and infectivity of recombinant HCV particles was investigated in vitro by incubation of genotype 2a chimeric virus Jc1 with bile and stool suspensions.
HCV RNA could be detected in 68 out of the 98 stool samples and and 16 samples also tested positive for HCVcoreAg. Presence of HCV RNA in stool was more frequent in male than in female and in patients with low platelet counts but was not associated with the detection of occult blood. Stool suspensions and to a lesser extent bile reduced the in vitro infectivity of genotype 2a chimeric Jc1 virus even though infection of Huh7 cells was not completely abrogated.
The researchers suggest that stool can be a potential source for HCV infection and thus unprotected anal intercourse should be avoided.
Frequent detection of HCV RNA and HCVcoreAg in stool of patients with chronic hepatitis C. Heidrich B, Steinmann E, Plumeier I et al. J Clin Virol. 2016 Apr 14;80:1-7 [Epub ahead of print]
Elastin fibre accumulation predicts hepatocellular carcinoma
Using a novel computational analysis, researchers found that elastin fibre was a predictor for the development of hepatocellular carcinoma (HCC), independently of collagen fibre and F stage.
The researchers, at Musashino Red Cross Hospital, Tokyo, enrolled 189 consecutive patients with HCV and advanced fibrosis. Using Elastica van Gieson-stained whole-slide images of pretreatment liver biopsies, collagen and elastin fibres were evaluated pixel by pixel (0.46 μm/pixel) and the cumulative incidences of HCC within three years were analyzed.
There was a significant correlation between collagen and elastin fibres, whereas variation in elastin fibre was greater than in collagen fibre. Both collagen fibre and elastin fibre were significantly correlated with F stage.
In total, 30 patients developed HCC during follow-up. Patients who had higher elastin fibre in addition to higher collagen fibre showed significantly higher incidences of HCC. With regard to elastin fibre, this difference remained significant in F3 patients. Furthermore, for patients with a higher collagen fibre amount, higher elastin was a significant predictor for HCC development.
Elastin fibre accumulation in liver correlates with the development of hepatocellular carcinoma. Yasui Y, Abe T, Kurosaki M et al. PLoS One. 2016 Apr 29;11(4):e0154558
HCV/HIV co-infection increases transplant waiting list mortality
HCV/HIV co-infection is a factor in mortality prior to liver transplantation and is associated with higher mortality on the waiting list, new evidence shows.
In a study at University Hospital Lozano Blesa, Zaragoza, Spain, among 199 patients with HCV enrolled for liver transplants between 1998 and 2015, 17 were also infected with HIV.
The patients with HCV/HIV co-infection had higher mortality on the waiting list than those with HCV monoinfection (35.3% versus 4.6%). The intention-to-treat survival analysis (ITTA) at one, three and five years was 75%, 64%, and 57% for HCV monoinfection and 52%, 47%, and 39% for HCV/HIV co-infection, respectively. The ITTA at one, three, six and 12 months was 96%, 91%, 87%, and 75% for HCV monoinfection and 76%, 70%, 64%, and 52% for HCV/HIV co-infection, respectively.
A Cox regression analysis was carried out including all variables with predictive value in the univariate analysis, showing that only donor age > 70 years (hazard ratio 3.12), UNOS 1 status (hazard ratio 10.1), MELD (hazard ratio 1.13), and HIV co-infection (hazard ratio 2.65) had independent negative predictive value for survival.
Intention-to-treat survival analysis of HCV/HIV co-infected liver transplant: Is it the waiting list? Araiz JJ, Serrano MT, García-Gil FA et al. Liver Transpl. 2016 Apr 26 [Epub ahead of print]
Prednisone/azathioprine effective in paediatric autoimmune hepatitis
In a new study, prednisone and azathioprine produced biochemical remission and significantly improved the prognosis of most children with autoimmune hepatitis (AIH), although there were significant side effects.
This was a retrospective analysis of the medical records of 15 patients with AIH, diagnosed before 18 years of age, treated in the Provincial Infectious Diseases Hospital in Bydgoszcz, Poland, between 2002 and 2013.
Biochemical remission of the disease was achieved on average after 36 days of treatment. Histopathological regression in the control liver biopsy was found in seven patients and progression in two patients.
Ten of the 15 patients experienced exacerbation of the disease from one to three times during observation, with an increase of ALT activity to greater than three norm, and the remaining five patients had no increase of ALT activity. In total, 10 patients in the study group experienced 17 exacerbations. In 13 cases of exacerbations, these were associated with a reduction in the dose of immunosuppressive drugs. There was no correlation between the biochemical exacerbation and changes in the histopathological image. Steroidside effects occurred in 14 patients.
The researchers suggest the significant side effects of treatment indicate the need for further exploration of effective and safe therapy, especially in the paediatric population.
Evaluation of the effectiveness of treatment with prednisone and azathioprine of autoimmune hepatitis in children. Pniewska A, Sobolewska-Pilarczyk M, Pawłowska M. Prz Gastroenterol. 2016;11(1):18-23
Growth impairment warning for children treated with PEG/INF/R
Impairment of growth should be considered as part of the risk-benefit profile of peg-interferon/ribavirin therapy in children with HCV, say researchers.
In a global open-label study, the team assessed the five-year follow-up of 107 children and adolescents with HCV who received peg-interferon and ribavirin for 24 or 48 weeks. Ninety-four patients were enrolled in the long-term follow-up part of the study and the median duration of follow-up was 287 weeks.
Of 63 with sustained virologic response enrolled on the study, 54 completed five years of follow-up and none relapsed in this time. Significant decreases in height Z scores were observed during treatment. The impact of treatment on height Z score was larger in patients treated for 48 weeks compared with those treated for 24 weeks (mean change from baseline to the end of treatment was -0.13 and -0.44 in the 24-week and 48-week treatment groups, respectively).
Among patients treated for 24 weeks, full recovery of height Z scores to baseline was observed by year one of follow-up, whereas only partial recovery was observed during five years of follow up in patients treated for 48 weeks (mean change from baseline to the final follow-up visit was -0.16 and -0.32 in the 24-week and 48-week treatment groups, respectively). Similar patterns were observed for weight and body mass index Z scores.
The researchers concluded that considerations should include both deferring treatment in patients during optimal growth periods, and the possibility of interferon-free regimens being available to children in the next five to 10 years.
Long-term follow-up of children treated with peginterferon and ribavirin for Hepatitis C virus infection. Haber B, Alonso E, Pedreira A et al. J Pediatr Gastroenterol Nutr. 2016 Apr 21 [Epub ahead of print]
Patients with autoimmune hepatitis may be at risk of diabetes
A new study suggests that many people with autoimmune hepatitis (AIH) may be at risk of diabetes mellitus (DM).
Researchers retrospectively analyzed 118 Japanese patients diagnosed with AIH from 1990 to 2014 at Nihon University School of Medicine. The prognosis of patients with and without DM was also compared.
Twenty-nine patients had DM and 21 received corticosteroids. The annual cumulative incidence rate of newly diagnosed DM was 1.2%. Multivariate analysis showed that DM occurred in older patients (odds ratio 6.290) and with higher serum immunoglobulin G levels (odds ratio 12.400).
A Cox hazard regression analysis revealed that predictive factors for DM were absence of other autoimmune diseases (odds ratio 0.171), use of corticosteroids (odds ratio 6.693) and lower platelet counts (odds ratio 1.873).
The 10-year survival rates of the DM and non-DM groups were 94.1% and 94.6%, respectively. There was no significant difference between these groups.
Prevalence and risk factors of diabetes mellitus in patients with autoimmune hepatitis. Matsumoto N, Ogawa M, Matsuoka S et al. Intern Med. 2016;55(8):879-85
Obesity epidemic linked to more childhood NAFLD
As a probable result of obesity, non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease seen in children today, say US reviewers.
The reviewers, from Alfred I duPont Hospital for Children, Wilmington and the Thomas Jefferson University, write that childhood obesity has reached epidemic proportions, and by 2012, more than one third of American children were overweight or obese. As a result, increasingly children are developing complications of obesity including liver disease. In fact, NAFLD disease is the most common form of chronic liver disease seen in children today.
Recently, there has been a burgeoning literature examining the pathogenesis, genetic markers, and role of the microbiome in this disease.
On the clinical front, new modalities of diagnosing hepatic steatosis and hepatic fibrosis are being developed to provide non-invasive methods of surveillance in children. Lastly, the mainstay of treatment of paediatric NAFLD has been largely through lifestyle interventions, namely, dieting and exercise. Currently, there are a number of clinical trials examining novel lifestyle and drug therapies for NAFLD that are registered with the US National Institutes of Health ClinicalTrials.gov website.
Paediatric non-alcoholic fatty liver disease. Uppal V, Mansoor S, Furuya KN.Curr Gastroenterol Rep. 2016 May;18(5):24
Telbivudine versus entecavir in HBV patients receiving chemotherapy
In chronic HBV patients receiving cytotoxic chemotherapy, telbivudine (LdT) showed lower clinical efficacy in viral suppression than entecavir (ETV) but was associated with greater extent of improvement in liver and renal functions, a new study found.
A total of 290 treatment-naïve chronic HBV patients undergoing intense chemotherapy at Tuen Mun Hospital, Hong Kong received daily 600 mg of LdT or 0.5 mg of ETV as pre-emptive antiviral chemoprophylaxis.
The ETV group had significantly higher proportion of patients with undetectable HBV DNA load compared to LdTat week 24 (72.99% compared to 50.33%). The cumulative rates of virological breakthrough in the LdT and ETV groups were 9.15% and 3.65% at the second year, respectively; this was associated with undetectable HBV DNA at week 24.
Compared with the ETV group, Model for End-stage Liver Disease score (year one: 4.53 versus 7.53) and estimated glomerular filtration rates (eGFRs) (year one: 118.17 versus 91.79 mL/min; year two: 111.14 versus 76.45 ml/min) in the LdT group were significantly improved from baseline after the first year. Moreover, a significant number of patients with impaired renal function had improved eGFRs after LdT than ETV treatment (32.68% versus 8.76%).
Comparison of clinical efficacy and renal safety of telbivudine and entecavir in chronic hepatitis B patients receiving cytotoxic chemotherapy. Law ST, Lee MK, Lee AS et al. J Dig Dis. 2016 Apr 16 [Epub ahead of print]
Metabolic disorders biggest risk for hepatocellular carcinoma
Metabolic disorders appear to be the biggest risk factors for hepatocellular carcinoma (HCC) and have increased in the last decade, new US evidence suggests.
Researchers at the National Cancer Institute, Bethesda, used data from the Surveillance, Epidemiology, and End Results-Medicare linkage to calculate population attributable fractions (PAFs) for each risk factor over time. A total of 10, 708 patients with HCC who were diagnosed between 2000 and 2011 were compared with 332,107 cancer-free controls residing in the Surveillance, Epidemiology, and End Results areas.
Overall, the PAF was greatest for metabolic disorders (32%), followed by HCV (20.5%), alcohol (13.4%), smoking (9%), HBV (4.3%), and genetic disorders (1.5%). The PAF for all factors combined was 59.5%. PAFs differed by race/ethnicity and sex. Metabolic disorders had the largest PAF among Hispanics (PAF, 39.3%) and whites (PAF, 34.8%), whereas HCV had the largest PAF among blacks (PAF, 36.1%) and Asians (PAF, 29.7%).
Between 2000 and 2011, the PAF of metabolic disorders increased from 25.8% to 36%. In contrast, the PAFs of alcohol-related disorders and HCV remained stable.
Population attributable fractions of risk factors for hepatocellular carcinoma in the United States. Makarova-Rusher OV, Altekruse SF, McNeel TS et al. Cancer.
Smoking plus HCV may affect the atherosclerotic process
A study from the University of Athens suggests a potentially synergistic effect of smoking and chronic HCV on the atherosclerotic process.
Researchers evaluated platelet microparticle (PMP) levels before and after treatment with pegylated-interferon-alfa and ribavirin in 28 chronic HCV patients compared with 20 non-alcoholic fatty liver disease (NAFLD) patients and 20 healthy volunteers.
Twenty-four of the HCV patients achieved sustained virological response (SVR). PMP levels were determined at baseline in HCV and NAFLD patients, and the volunteers, at end-of-treatment (EOT) and 24 weeks post-treatment (SVR24) in the HCV patients.
PMP levels at baseline were higher in the HCV than in the NAFLD patients and volunteers. Higher PMPs at baseline were observed in smokers than non-smokers with HCV. Among smokers from all groups, PMPs at baseline were higher in the HCV than the NAFLD patients or volunteers.
In the HCV patients, PMPs declined from baseline to both EOT and SVR24. Only HCV patients with SVR had a significant decline in PMPs from baseline to SVR24. PMPs at ΕΟΤ and SVR24 in all HCV patients were similar to PMPs in NAFLD patients and volunteers.
The researchers concluded that PMP levels are increased in HCV patients, particularly smokers, which further supports the atherosclerotic potential of HCV and suggests a potentially synergistic effect of smoking and HCV on the atherosclerotic process. Since PMP levels in HCV patients with SVR were similar to NAFLD patients and volunteers, the atherosclerotic potential of HCV seems to be abolished by effective antiviral treatment.
The significance of platelet microparticles in patients with chronic hepatitis C and their association with antiviral treatment and smoking. Kanellopoulou T, Alexopoulou A, Kontopidou FN et al. Ann Gastroenterol. 2016 Apr-Jun;29(2):201-7
High survival rates in IFN-treated HCV cirrhosis patients with SVR
A study found that patients with compensated HCV cirrhosis who achieved a sustained virologic response (SVR) when treated with interferon (IFN) had a survival rate similar to the general population.
Researchers studied surveillance data from three cohorts of Italian patients with compensated HCV cirrhosis who achieved SVR on an IFN-based regimen, compared to simultaneously observed non-SVR, untreated and decompensated patients. Overall survival was calculated from the date of start of IFN to death.
Overall, 28 of 181 patients followed-up for a median period of 9.6 years died. The 10 and 20-year overall survival rates for the whole series were 90.9% and 62.9%, respectively. The number of expected deaths in the corresponding age and sex matched general population was 28.1, corresponding to a standardized mortality ratio (SMR) of 1.00, with an SMR for non-SVR patients of 3.85, for untreated of 3.01 and for decompensated of 6.70.
Survival of patients with HCV cirrhosis and sustained virologic response is similar to the general population. Bruno S, Di Marco V, Lavarone M et al. J Hepatol. 2016 Mar 23 [Epub ahead of print]
Does arsenic in drinking water increase risk of hepatitis or cirrhosis?
A study in Taiwan found that high concentrations of arsenic in drinking water significantly increased the risk of hepatitis or cirrhosis in people without chronic viral hepatitis. However, the study also found that, in people with chronic viral hepatitis, lower levels significantly reduced the risk.
Researchers examined associations between exposure of arsenic in drinking water and risk of hepatitis and cirrhosis, and the interaction with chronic viral hepatitis, in 4,387 people living in the Lanyang Basin of northeastern Taiwan, where well water has an arsenic content that ranges from undetectable to 3590 μg/L.
The prevalence odds ratios in the overall study population for chronic hepatitis or cirrhosis for well water arsenic concentrations of =10 μg/L were 1.00 (reference), 0.93 for 10.1-49.9 μg/L, 1.24 for 50.0-99.9 μg/L, 0.98 for 100.0-299.9 and 1.86 for =300.0 μg/L.
Increasing levels of arsenic in drinking water were associated with increasing prevalence of chronic hepatitis or cirrhosis in residents who were seronegative for HBsAg and seronegative for anti-HCV, but not for seropositive for either HBsAg or anti-HCV.
In individuals who were seropositive for HBsAg or anti-HCV, there was an inverse association between hepatitis or cirrhosis and consumption of water with levels of arsenic =100.0μg/L. Among participants who were seropositive for HBsAg or anti-HCV, consumption of water with levels of arsenic =100.0 μg/L was associated with a reduced risk of liver cancer (multivariate-adjusted hazard ratio, 0.29). A higher proportion of individuals exposed to cumulative arsenic level >14,000μg/L× year were carriers of inactive HBV and were positive for HBsAg (60%) than individuals exposed to water below this arsenic level (35%).
Effects of arsenic in drinking water on risk of hepatitis or cirrhosis in persons with and without chronic viral hepatitis. Hsu LI, Wang YH, Hsieh FI et al. Clin Gastroenterol Hepatol. 2016 Apr 6 [Epub ahead of print]
No link between smoking and liver disease in HIV/HCV coinfection
A new study suggests tobacco smoking is not associated with accelerated progression of liver disease in HIV-HCV co-infected individuals.
This is despite it being shown to be an independent risk factor for liver fibrosis in people with HCV.
The study population consisted of participants from the Canadian Co-infection Cohort multi-centre study of HIV/HCV co-infected individuals from 2003 to 2014. Data were analyzed for all participants who did not have significant fibrosis or end-stage liver disease (ESLD) at baseline. Of 1,072 participants, 978 had never smoked, 817 were current smokers, and 161 were previous smokers.
Tobacco exposure was not associated with accelerated progression to significant liver fibrosis nor with ESLD when comparing ever versus never smokers (odds ratios 1.06 and 1.20, respectively) or increases in pack-years smoked (odds ratios 1.05 and 0.94, respectively).
However, the study found that both time-updated alcohol use in the previous six months and presence of detectable HCV ribonucleic acid were associated with aspartate-to-platelet ratio index (APRI) score =1.5.
Tobacco smoking is not associated with accelerated liver disease in human immunodeficiency virus-hepatitis C coinfection: a longitudinal cohort analysis. Costiniuk CT, Brunet L, Rollet-Kurhajec KC et al. Open Forum Infect Dis. 2016 Mar 7;3(2):ofw050 .
HRQoL in Asians with hepatocellular carcinoma
Asians with hepatocellular carcinoma (HCC) appear to have a better health-related quality of life (HRQoL) than Europeans with the same condition, new evidence suggests.
In a multinational study, 227 patients with HCC from Asian and European countries completed the EORTC QLQ-C30 and the EORTC QLQ-HCC18 questionnaires.
After adjusting for demographic and clinical characteristics, Asian patients still had significantly better HRQoL scores in emotional functioning, insomnia, (QLQ-C30) and in sexual interest (QLQ-HCC18). Researchers also found an interaction in physical functioning (QLQ-C30) and fatigue (QLQ-HCC18) between geographic region and marital status; married Europeans having worse HRQoL scores than Asian singles.
The researchers suggest cultural differences, as well as clinical differences in the pattern of disease owing to active surveillance of Asian countries may explain the results.
Differences in health-related quality of life between European and Asian patients with hepatocellular carcinoma. Chie WC, Blazeby JM, Hsiao CF et al. Asia Pac J Clin Oncol. 2016 Apr 1 [Epub ahead of print]
NAFLD becoming global principal cause of chronic liver disease
Non-alcoholic fatty liver disease (NAFLD) is becoming the principal cause of chronic liver disease across the world and disproportionately affects different ethnic groups in the USA.
That’s according to a literature review of NAFLD and its subtype non-alcoholic steatohepatitis (NASH) from Howard University, Washington, DC.
It also found that, in the US, Hispanics are the most disproportionately affected ethnic group with hepatic steatosis, and elevated aminotransferase levels, whereas African-Americans are the least affected.
Genetic disparities involved in lipid metabolism seem to be the leading explanation for the lowest incidence and prevalence of both NAFLD and NASH in African-Americans.
The reviewers suggest this unprecedented rise requires an initiation of population cohort studies with long-term follow-up to determine the incidence and natural history of NAFLD and it’s under representation in African-Americans. Future studies should also focus on the delineation of the interplay between genetic and environmental factors that trigger the development of NAFLD and NASH.
Global epidemiology of nonalcoholic fatty liver disease and perspectives on US minority populations. Sherif ZA, Saeed A, Ghavimi S et al. Dig Dis Sci. 2016 Apr 1. [Epub ahead of print]
Benefits of sofosbuvir-based combinations in HCV
In a study at the Cleveland Clinic (1) the combination of sofosbuvir (SOF) and simeprevir (SIM) without riba virin (R) was well tolerated and resulted in high virological response rates in recurrent HCV GT1 infection after liver transplantation (LT).
Sixty-seven patients with HCV GT1 have received SOF+SIM following LT to date: 39% with HCV RNA >6,000,000 IU/mL, 22% with advanced hepatic fibrosis (stage 3-4), 6% with homeostatic recurrence and 58% had previously failed or did not tolerate interferon-based treatments. Mean time from LT to treatment was 6.1 years. All patients had estimated GFR >30 mL/min. Tacrolimus was primary immunosuppression in 84% of patients and minimal immunosuppression dose adjustments were required during treatment.
In intention to treat analysis, 90% achieved end of treatment virologic response and 88% achieved sustained virologic response.
And in a review from the Université Paris Descartes (2), authors wrote that results from clinical studies as well as preliminary real-life data regarding the combination of SOF (a nucleotide polymerase inhibitor) and daclatasvir, a first-in-class NS5A replication complex inhibitor, demonstrate that it is one of the most promising antiviral therapies for HCV, with once-daily oral dosing, a low pill burden, good tolerability, and limited drug-drug interactions, in addition to high antiviral potency, with over 90% sustained virologic response rates.
This combination has high pangenotypic antiviral potency regardless of the severity and patient characteristics. The combination of SOF and an NS5A inhibitor with R for 12 weeks appears to be a very good further treatment option in both cirrhotic and treatment-experienced patients whatever the stage of fibrosis.
Sofosbuvir and simeprevir without ribavirin effectively treat Hepatitis C Virus Genotype 1 infection after liver transplantation in a two-center experience. Jackson WE, Hanouneh M, Apfel T et al.Clin Transplant. 2016 Mar 28 [Epub ahead of print]
Daclatasvir-sofosbuvir combination therapy with or without ribavirin for hepatitis C virus infection: from the clinical trials to real life. Pol S, Corouge M, Vallet-Pichard A. Hepat Med. 2016 Mar 4;8:21-26.
High-fat, high-fructose diet may increase risk of NAFLD
New animal research suggests that a high-fat, high-fructose diet may increase the risk and progression of nonalcoholic fatty liver disease (NAFLD).
In a study at Khon Kaen University, Thailand, the effects of a high-fat, high-fructose diet (HFFD) on mRNA levels and activities of the antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), were determined in mouse livers and brains.
Histopathology of the liver showed that fat accumulation and inflammation depended on the period of the HFFD-consumption. The levels of mRNA and enzymatic activities of SOD, CAT, and GPx were raised, followed by the increases in malondialdehyde levels in livers and brains of the HFFD mice. The oxidized GSSG content was increased while the total GSH and the reduced GSH were decreased, resulting in the increase in the GSH/GSSG ratio in both livers and brains of the HFFD mice.
A high-fat, high-fructose diet induces antioxidant imbalance and increases the risk and progression of nonalcoholic fatty liver disease in mice. Jarukamjorn K, Jearapong N, Pimson C et al. Scientifica (Cairo) ;2016:5029414
Sequential ETV/PEG-IFN “promising” in HBV
Researchers claimed “promising results” using a sequential combined therapy with entecavir (ETV) and pegylated interferon (PEG-IFN) in young patients with active chronic HBV.
In a study at the University of Turin, 39 patients with different HBV genotypes, HBeAg-positive/negative received a sequential therapy with ETV 0.5 mg/day monotherapy for 12 weeks followed by combination of ETV and PEG-IFN α-2a 180µg/week for 12 weeks, then PEG-IFN monotherapy for 36 weeks.
HBeAg seroconversion rate was 68.2%; HBsAg loss was 33.3%; sustained virological response was 64.1%; primary non-response was observed in eight patients after 12 weeks of PEG-IFN therapy; virological relapse was reported in six patients. Viral genotype and HBsAg decline were the most important predictive factor for PEG-IFN response.
The researchers commented that the stopping rule after 12 weeks of PEG-IFN therapy was useful for identify the non-responders. They added that their results should not be generalized, as further investigations were required for the confirmation of this combination approach.
Sequential therapy with entecavir and pegylated interferon in a cohort of young patients affected by chronic hepatitis B. Boglione L, Cariti G, Di Perri G et al. J Med Virol. 2016 Mar 27 [Epub ahead of print]
High prevalence of hepatitis in African immigrants
The high prevalence of viral hepatitis, particularly HBV, in immigrants from Africa represents a challenge for healthcare systems.
The Spanish study highlighted that viral hepatitis is a significant health problem in African countries, from which there has been an increase in the immigrant population.
Researchers at the Hospital de Poniente, El Ejido, studied 2,518 immigrant patients (87.7% Sub-Saharan natives), with a mean age of 31.3 years.
Some 78.8% of the patients had a positive infection marker for HBV, and 638 (25.3%) were diagnosed with active HBV. In 19 cases, antibodies against HDV were detected (four cases with detection of the viral genome). Sixty-eight patients had antibodies against HCV, 26 of whom had a positive viral load.
The researchers concluded this high prevalence of viral hepatitis represent a significant change in the profile of patients treated in Spain, and requires measures aimed at early diagnosis and transmission prevention.
Viral hepatitis and immigration: a challenge for the healthcare system. Cuenca-Gómez JA, Salas-Coronas J, Soriano-Pérez MJ et al. Rev Clin Esp. 2016 Mar 16 [Epub ahead of print]
Chloroquine has potential for HCV non-responders
A pilot study suggests chloroquine (CQ), an autophagy inhibitor used to treat malaria, may be a treatment option for HCV non-responders.
Researchers from Iran and the USA studied 10 patients with chronic HCV genotype 1 who were unresponsive to a combination of pegylated interferon alpha and ribavirin. They were randomized to CQ (150 mg daily for eight weeks) or placebo, and were followed for four weeks after CQ therapy. HCV RNA load and plasma alanine transaminase (ALT) levels were measured at baseline, week four (initial response), week eight (end-of-treatment response), and at the end of 12 weeks.
A significant decrease in HCV RNA after the treatments (week eight) was seen in all patients in the CQ group. However, HCV RNA levels increased within four weeks after discontinuation of CQ treatment although they were still lower than baseline. In addition, the ALT normalised during treatment in the CQ group. However, this response was also lost after treatment cessation.
New use of an old drug: chloroquine reduces viral and ALT levels in HCV non-responders (a randomized, triple-blind, placebo-controlled pilot trial). Peymani P, Yeganeh B, Sabour S et al. Can J Physiol Pharmacol. 2016 Jan 15:1-7 [Epub ahead of print]
Metabolic disorders biggest risk for hepatocellular carcinoma
Metabolic disorders appear to be the biggest risk factors for hepatocellular carcinoma (HCC) and have increased in the last decade, new US evidence suggests.
Researchers at the National Cancer Institute, Bethesda, used data from the Surveillance, Epidemiology, and End Results-Medicare linkage to calculate population attributable fractions (PAFs) for each risk factor over time. A total of 10, 708 patients with HCC who were diagnosed between 2000 and 2011 were compared with 332,107 cancer-free controls residing in the Surveillance, Epidemiology, and End Results areas.
Overall, the PAF was greatest for metabolic disorders (32%), followed by HCV (20.5%), alcohol (13.4%), smoking (9%), HBV (4.3%), and genetic disorders (1.5%). The PAF for all factors combined was 59.5%. PAFs differed by race/ethnicity and sex. Metabolic disorders had the largest PAF among Hispanics (PAF, 39.3%) and whites (PAF, 34.8%), whereas HCV had the largest PAF among black people (PAF, 36.1%) and Asians (PAF, 29.7%).
Between 2000 and 2011, the PAF of metabolic disorders increased from 25.8% to 36%. In contrast, the PAFs of alcohol-related disorders and HCV remained stable.
Population attributable fractions of risk factors for hepatocellular carcinoma in the United States. Makarova-Rusher OV, Altekruse SF, McNeel TS et al. Cancer. 2016 Mar 21 [Epub ahead of print]
High-dose atorvastatin increases risk of hepatotoxicity
A UK study suggests an increased risk of hepatotoxicity with high doses of the statin atorvastatin when compared to sim vastatin.
Researchers at the University of Glasgow used the UK General Practice Research Database (GPRD) to identify 164,407 patients with a first prescription for sim vastatin and 76,411 with atorvastatin between 1997 and 2006. None of the patients had a prior record of liver disease, alcohol-related diagnosis, or liver dysfunction.
Moderate to severe hepatotoxicity developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio for all atorvastatin relative to simvastatin was 1.9.
High dose was classified as 40-80mg daily and low dose 10-20mg daily. Hepatotoxicity occurred in 0.44% of 4,075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS].
Adjusted hazard ratios compared to LDS were 7.3 for HDA, 1.4 for LDA and 1.5 for HDS.
High dose atorvastatin associated with increased risk of significant
hepatotoxicity in comparison to simvastatin in UK GPRD cohort. Clarke AT, Johnson PC, Hall GC et al. PLoS One. 2016 Mar 16;11(3):e0151587
Green tea component may have anti-HBV properties
New research suggests epigallocatechin-3-gallate (EGCG), a major component of green tea, could be an effective anti-HBV agent.
Using fluorescence quenching and affinity binding, researchers at Henan Agricultural University, Zengzhou, China, showed EGCG to be an important transcriptional regulator of the HBV genome. It achieves this by interacting with farnesoid X receptor alpha (FXRα).
Luciferase assay showed that EGCG effectively inhibited the transcription of the HBV promoter dose-dependently when expression plasmids of FXRα and retinoid X receptor α (RXRα) were co-transfected into HEK293 cells.
These results indicated the down-regulation of the HBV antigen and the decrease in the transcriptional activation of the HBV EnhII/core promoter by FXRα/RXRα are mainly because of the interaction between EGCG and FXRα. Therefore, say the researchers, EGCG, an antagonist of FXRα in liver cells, has the potential to be employed as an effective anti-HBV agent.
Epigallocatechin gallate inhibits hepatitis B virus via farnesoid X receptor alpha. Xu J, Gu W, Li C et al. J Nat Med. 2016 Mar 11. [Epub ahead of print]
Identifying and staging HCV and fibrosis with common electronic medical record systems
HCV infections can be identified and fibrosis staged using commonly available electronic medical record (EMR)-based algorithms.
So say researchers at the NorthShore University Health System, Portland, USA. The team performed a pilot study to identify all HCV-infected patients in a large healthcare system, and predict their fibrosis stage on the basis of demographic and laboratory data from their EMRs.
The liver biopsies of 191 HCV patients were graded using the Ishak and Metavir scoring systems. Demographic and laboratory data were extracted from the EMR and used to calculate the aminotransferase to platelet ratio index, Fib-4, Fibrosis Index, Forns, Göteborg University Cirrhosis Index, Lok Index and Vira-HepC.
In total, 869 HCV-infected patients were identified from a population of more than 1m. In the subgroup of patients with liver biopsies, all seven algorithms were significantly correlated with the fibrosis stage. The degree of correlation was moderate, with correlation coefficients ranging from 0.22 to 0.60.
For the detection of advanced fibrosis (Metavir three or four), the areas under the receiver operating characteristic cure ranged from 0.71 to 0.84, with no significant differences between the individual scores. Sensitivities, specificities, and positive and negative predictive values were within the previously reported range. All scores tended to perform better for higher fibrosis stages.
Identification and fibrosis staging of Hepatitis C patients using the electronic medical record system. Anand V, Hyun C, Khan QM et al. J Clin Gastroenterol. 2016 Mar 11. [Epub ahead of print]
Obesity a major risk factor for cirrhosis and advanced fibrosis
Obesity has been shown to be the major risk factor for cirrhosis and advanced fibrosis in young Hispanic males.
Researchers studied 2,466 participants in the community-based Cameron County Hispanic Cohort in South Texas. Aspartate transaminase to Platelet Ratio Index (APRI) was used to predict cirrhosis.
The prevalence of cirrhosis using APRI=2 was 0.94%, which is nearly four-fold higher than the national USA prevalence. Using APRI=1, the overall prevalence of cirrhosis/advanced fibrosis was 3.54%. In both analyses, the highest prevalence was in males, specifically in the 25-34 age group.
Risk factors independently associated with APRI=2 and APRI=1 included HCV, diabetes and central obesity with a remarkable population attributable fraction of 52.5% and 65.3% from central obesity, respectively.
Excess alcohol consumption was also independently associated with APRI=2. The presence of patatin-like phospholipase domain-containing-3 gene variants was independently associated with APRI=1 in participants over 50 years of age.
Cirrhosis and advanced fibrosis in Hispanics in Texas: the dominant contribution of central obesity. Jiao J, Watt GP, Lee M et al. PLoS One. 2016 Mar 7;11(3):e0150978
Care for HBV mothers is inadequate following pregnancy
New evidence from the USA suggests HBV care for chronically infected mothers may be inadequate following pregnancy.
Researchers assessed the quality of HBV care in 243 HBsAg-positive mothers who had sought pre-natal care at Massachusetts General Hospital.
More than a third of the women were first diagnosed with HBV infection at a pre-natal visit, and one third did not undergo timely liver function test measurements. HBV DNA was never measured in 26% and was untimely in 34% of patients.
One were at high-risk for HCC based on American Association for the Study of Liver Diseases (AASLD) criteria, yet only 33% of these women underwent timely imaging. Nearly half never saw a liver specialist for their HBV care.
In multivariate analysis, women were 3.7 times more likely to have a timely ALT and 8.1 times more likely to have a timely HBV DNA if they were followed by a liver specialist.
The researchers say the HBV care was remarkably inadequate and discontinuous. They suggest that, as HBV infection is already being
identified pre-natally, quality improvement measures encompassing obstetricians, primary care providers and hepatologists are needed to ensure that HBV-infected women are linked to care post-pregnancy.
Discontinuity of care for mothers with chronic hepatitis B diagnosed during pregnancy. Rajbhandari R, Barton K, Juncadella AC et al. J Viral Hepat. 2016 Mar 4 [Epub ahead of print]
Daclatasvir/peginterferon-ribavirin most effective regimen in HCVg1
Daclatasvir plus peginterferon-ribavirin (PR) was the most effective direct-acting antiviral agent regimen in SVR12 and SVR24, but carried an increased adverse events profile in HCV genotype one.
Researchers at Wenzhou Medical University, China, conducting a literature review found 22 eligible randomised controlled trials. Compared with PR, daclatasvir plus PR (odds ratio 8.90), faldaprevir plus PR (odds ratio 3.72), simeprevir plus PR (odds ratio 3.59) and sofosbuvir plus PR (odds ratio 4.69) yielded a significant effect in improving SVR12. Consistently, simeprevir plus PR (odds ratio 3.49), sofosbuvir plus PR (odds ratio 4.51) and daclatasvir plus PR (odds ratio 4.77) also improved the rates of SVR24.
With respect to adverse events, compared with PR, ledipasvir plus sofosbuvir plus PR (odds ratio 2.13) conferred a significant advent event in nausea, whereas daclatasvir plus PR (odds ratio 0.20 and 0.18, respectively) lowered the incidence of fatigue and nausea significantly when compared with ledipasvir plus sofosbuvir plus PR.
Systematic review and network meta-analysis of randomised controlled trials: comparative effectiveness and safety of direct-acting antiviral agents for treatment-naive Hepatitis C Genotype 1. Zhu GQ, Zou ZL, Zheng JN et al. Medicine (Baltimore). 2016 Mar;95(9):e3004
High global prevalence of HCV in people with HIV
There is a high global prevalence of HCV in all people with HIV, particularly those who inject drugs.
A global systematic review and meta-analysis carried out by an international team of researchers found 783 studies published between 2002 and 2015, resulting in 902 estimates of the prevalence of HIV/HCV co-infection.
The analysis showed co-infection was present in 2.4% of those with HIV within general population samples, 4.0% within pregnant or heterosexually exposed samples, 6.4% in men who have sex with men, and 82.4% in people who inject drugs.
The odds of HCV infection were six times higher in people living with HIV (5.8) than their HIV-negative counterparts.
Worldwide, there were 37million people infected with HIV and 115million people with antibodies to HCV. The study found approximately 2,278,400 HIV/HCV co-infections, of which 1,362,700 were in people who inject drugs, equalling an overall co-infection prevalence in HIV-infected individuals of 6.2%.
The research, which was funded by the World Health Organization, highlighted the importance of routine HCV testing in all HIV-infected individuals, but especially in people who inject drugs. It also identified a need to improve country-level surveillance of HCV prevalence across different population groups in all regions.
Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Platt L, Easterbrook P, Gower E et al. Lancet Infect Dis. 2016 Feb 24 [Epub ahead of print]
Success of a UK campaign in identifying new hepatitis cases
Offering routine blood-borne virus (BBV) screening in emergency departments (EDs) uncovered a high number of hepatitis, particularly HCV, infections.
During the "Going Viral" campaign (13-19 October 2014), nine UK EDs in Glasgow, Leeds, Leicester and London offered adults having blood taken as part of routine care HIV, HBV and HCV tests. The areas involved all have high HIV prevalence and patients who tested positive were linked to care.
A total of 7,807 patients had blood taken during their ED visit and 2,118 were tested for BBVs. In all, 71 tests were positive, with 32 resulting in a new diagnosis. There were 39 HCV infections (15 newly diagnosed), 17 HIV infections (six newly diagnosed), and 15 HBV infections (11 newly diagnosed). Those aged between 25 and 54 had the highest prevalence: 2.46% for HCV, 1.36% for HIV and 1.09% for HBV.
The study authors calculated that, assuming the cost per diagnosis was £7, the cost per new case detected would be £988 for HCV, £1,351 for HBV and £2,478 for HIV. The authors also concluded that testing for HIV alone would have missed 54 viral hepatitis diagnoses (26 new), supporting further evaluation of routine BBV testing in UK EDs.
Incorporating HIV/hepatitis B virus/hepatitis C virus combined testing into routine blood tests in nine UK Emergency Departments: the "Going Viral" campaign. Orkin C, Flanagan S, Wallis E et al. HIV Med. 2016 Mar;17(3):222-30
Telbivudine superior to other NAs in HBV outcomes
At one year, telbivudine was superior to other nucleos(t)ide analogues (NAs) in HBeAg seroconversion, among other outcomes, in chronic HBV.
Researchers at Nanfang Hospital, Guangzhou, China, conducted a comprehensive and up-to-date network meta-analysis comparing the efficacy of NAs in patients with chronic HBV. A total of 75 randomised controlled trials (RCTs) were included in the systematic review, which was funded by Novartis.
At one year, telbivudine was associated with significantly higher rates of HBeAg seroconversion than adefovir (odds ratio 1.99), entecavir (odds ratio 2.00) and limivudine (odds ratio 1.49). It was linked to with significantly higher HBeAg loss than entecavir (odds ratio 1.85) and limivudine (odds ratio 1.62), with significantly higher aminotransferase (ALT) normalisation than limivudine (odds ratio 1.50), and with significantly higher rates of HBV DNA suppression than adefovir (odds ratio 2.77) and limivudine (odds ratio 2.97).
At two years, however, the relative efficacy outcomes were not statistically significant.
Effect of telbivudine versus other nucleos(t)ide analogs on HBeAg seroconversion and other outcomes in patients with chronic Hepatitis B: a network meta-analysis. Liang X, Fan R, Sun J et al. Adv Ther. 2016 Feb 26. [Epub ahead of print]
UK Somali population ‘needs HBV education’
Promoting HBV testing and contact tracing and countering misconceptions of the virus among migrant Somali populations in the UK, should be a priority.
Researchers at the University of Bristol canvassed the views of 30 people with Somali ethnicity living in the area through focus groups and semi-structured interviews.
Most participants lacked awareness of HBV and often identified it with 'jaundice'. There were frequent misconceptions regarding transmission, natural history and diagnosis, with the infection commonly viewed as a relatively trivial, short lived, symptomatic disease. HBV was generally not stigmatised. Lack of understanding of the disease was cited as the major barrier to targeted testing and contact tracing.
Barriers and opportunities for hepatitis B testing and contact tracing in a UK Somali population: a qualitative study. Cochrane A, Collins P, Horwood JP. Eur J Public Health. 2016 Feb 15 [Epub ahead of print]
Chinese and western medicine can cause DILI
Both Chinese herbal medicine (CHM) and Western medicine (WM) can lead to drug-induced liver injury (DILI), but with different clinical characteristics, say researchers.
Overall, 1,985 DILI cases were retrospectively collected from 96,857 patients hospitalised because of liver dysfunction in Beijing’s 302 Military Hospital between January 2009 and January 2014.
In the DILI patients, CHM was implicated in 563 cases, 870 cases were caused by WM. In the remaining patients, accounting for 27.8% of the cohort, the combination of WM and CHM was blamed. Polygonum multiflorum was the major implicated CHM.
The cases caused by CHM were more female (51% versus 71%) and positive rechallenge (6.1% versus 8.9%), a much greater proportion of hepatocellular injury (62.2% versus 88.5%), and a higher mortality (2.8% versus 4.8%). However, no differences in the rates of chronic DILI and ALF were found (12.9% versus 12.4%; 7.6% versus 7.6%, respectively).
Based on Roussel Uclaf Causality Assessment Method, 75.6% of cases caused by CHM were classified as probable and only 16.6% as highly probable, significantly different from WM (38.4% and 60.3%).
Comparison between Chinese herbal medicine and western medicine-induced liver injury of 1985 patients. Zhu Y, Niu M, Chen J et al. J Gastroenterol Hepatol. 2016 Feb 20 [Epub ahead of print]
Statins reduce cirrhosis and HCC in HCV patients
Statins have been associated with a dose-dependent reduction in incident cirrhosis and hepatocellular carcinoma (HCC) among patients with HCV (1).
In the ERCHIVES study, among 9,135 HCV patients, 1,649 developed cirrhosis, and 239 developed incident HCC. Statin use was associated with a 44% reduction in development of cirrhosis (adjusted hazard ratio 0.6). The adjusted hazard ratios of fibrosis progression with statin cumulative defined daily dose (cDDD) 28-89, 89-180, and >180, were 0.74, 0.71, and 0.6 (0.53,0.68), respectively.
Mean change in FIB-4 score with atorvastatin (944) and fluvastatin (34) was -0.17 and -0.13 respectively after adjustment for baseline FIB-4 score and established predictors of cirrhosis. Statin use was also associated with a 49% reduction in incident HCC (adjusted hazard ratio 0.51). A similar dose-response relationship was observed.
However, a US study found statins were used less frequently in patients with HCV compared to those without (2).
In the study of 157 people at W. G. Hefner Veterans Affairs Medical Centre, , a significant difference in statin use was seen between those with and without HCV (54% versus 83%). Although there were a greater number of subjects on statins in the non-HCV group, there was not a significant difference in the proportion of subjects reaching their LDL goal between the two groups.
1) Atorvastatin and fluvastatin are associated with dose-dependent reductions in cirrhosis and HCC, among patients with HCV. Results from ERCHIVES. Simon TG, Bonilla H, Yan P et al. Hepatology. 2016 Feb 18 [Epub ahead of print]
2) Treatment of dyslipidemia with statins by primary care providers in Veterans with and without chronic Hepatitis C. Chandra R, Dolder NM, Dolder CR et al.Am J Health Syst Pharm. 2016 Mar 1;73(5 Suppl 1)
High adherence to ribavirin during PEG-interferon in chronic HCV
A real time study in the Netherlands found that adherence to ribavirin during PEG-interferon containing therapy in chronic HCV was high.
In this randomized controlled trial at the University Medical Centre of Utrecht, 35 patients (the intervention group) received a medication dispenser that monitored ribavirin intake real-time during 24 weeks of PEG-interferon/ribavirin±boceprevir or telaprevir. Thirty-seven patients in a control group received standard-of-care. Adherence was also measured by pill count.
Median adherence by pill count was 96% with 30 (94%) of patients exhibiting 80% adherence. Perfect adherence (i.e. 100%) was similar in intervention and control groups: 22 (85%) versus 15 (75%). Adherences by real-time medication monitoring and by pill count did not correlate. No predictors of poor adherence could be identified.
Ribavirin trough levels after eight weeks (median: 2.4mg/L versus 2.7mg/L) and 24 weeks (median: 3.0mg/L versus 3.0mg/L), and virological responses did not differ between the intervention and control groups.
Adherence to ribavirin in chronic hepatitis C patients on antiviral treatment: results from a randomized controlled trial using real-time medication monitoring. van Vlerken LG, Lieveld FI, van Meer S et al. Clin Res Hepatol Gastroenterol. 2016 Feb 8 [Epub ahead of print]
Ezetimibe/peg-IFN/RBV benefits obese HCV patients
Adding ezetimibe to pegylated interferon and ribavirin (peg-IFN/RBV) significantly improved early virological response rates in obese chronic HCV patients.
In a study at Al-Azhar University, Cairo, 144 chronic HCV genotype four patients were divided into two groups; group 1 included 76 non-obese patients and group two 68 obese patients. Each group was further sub-classified into equal control and treated groups. The control groups received peg-IFN/RBV combination for 24 weeks, and the treated groups received peg-IFN/RBV plus ezetimibe for 12 weeks and then only peg-IFN/RBV for the remaining 12 weeks
Early virological response significantly improved in the obese patients (85.3% versus 64.7% in the treated and control groups, respectively) without any significant improvement in the non-obese patients. Biochemical responses (defined as normalisation of alanine aminotransferase at week 12) were markedly improved in the treated groups in both the non-obese and obese groups compared with their respective controls.
Coadministration of ezetimibe with pegylated interferon plus ribavirin could improve early virological response in chronic hepatitis C obese Egyptian patients. Helal GK, Gad MA, Abd-Ellah MF et al. Eur J Gastroenterol Hepatol. 2016 Feb 11. [Epub ahead of print]
Diabetes, smoking and alcohol increase risk of hepatocellular carcinoma
Two studies have found diabetes, smoking, alcohol and HBV to be among the main risk factors for hepatocellular carcinoma (HCC) and its mortality.
Researchers from the National Taiwan University College of Medicine followed up 51,164 participants. They were aged 44 to 94, did not have chronic HBV or HCV, and were enrolled from nationwide health screening units (1) . Between 1998 and 2008 there were 253 deaths from HCC. A history of diabetes was associated with deaths from HCC for both total participants (adjusted hazard ratio 2.97 ) and ever smokers with current or past smoking habits (hazard ratio 1.92).
Both never smokers (hazard ratio 0.46) and quitters (hazard ratio 0.62) had a lower adjusted risk of HCC deaths compared with current smokers. Among all ever smokers with current or past smoking habits, as compared with diabetic smokers, only quitters without diabetes had a lower adjusted risk of HCC deaths (hazard ratio 0.37). However, quitters with diabetes had a similar risk of deaths from HCC when compared with smokers with diabetes.
The researchers concluded that clinicians should promote diabetes and smoking prevention in order to reduce subsequent HCC mortality, even in adults without chronic viral hepatitis.
Another study, from China, concluded HBV and alcohol intake were still the major risk factors for HCC (2).
Researchers at Xiamen University conducted a case-control study of 314 HCC cases and 346 controls was conducted in Xiamen, which is an epidemic area in China for both HBV and HCC. Face-to-face interviews were conducted and enzyme-linked immunosorbent assay kits were used to determine the status of serological markers of HBV infection.
As expected, HBV and alcohol intake remained the major risk factors of HCC. Liver disease history and passive smoking are also associated with elevated HCC risk. Indoor air pollution and pesticide exposure were newly identified as risk factors. The researchers suggested alcohol prevention should be promoted and that the consumption of fruit and tea intake could significantly lower the HCC risk .
1) The relationship of diabetes and smoking status to hepatocellular carcinoma mortality. Chiang CH, Lu CW, Han HC et al. Medicine (Baltimore). 2016 Feb;95(6):e2699
2) The epidemiological investigation on the risk factors of hepatocellular carcinoma: a case-control study in Southeast China. Niu J, Lin Y, Guo Z et al. Medicine (Baltimore). 2016 Feb;95(6):e2758
HBV patients live longer with simultaneous liver-kidney transplants
Although HBV patients who received simultaneous liver-kidney transplant (SLKT) had higher early-stage infection rates, they had higher long-term survival rates than those who received liver transplant (LT) alone.
In a study at the Organ Transplant Centre of the Shanghai First People's Hospital, 21 patients with HBV and renal failure (any degree) underwent SLKT and 25 underwent LT alone.
The one, three and five year survival rates of the SLKT recipients were 90.5%, 81.0%, and 81.0%, respectively. The incidence of acute hepatic allograft rejection between SLKT recipients and LT recipients (33% versus 16%) did not reach significance. Despite higher infection rate, more prevalent HBV relapse, and longer stays in the intensive care unit, the SLKT recipients experienced 90.5% one-year survival rates compared with 60% amongst the LT recipients.
Multivariate regression analysis revealed that post-operative renal failure (odds ratio 48) and Risk/Injury/Failure/Loss/End-stage (RIFLE) stage (odds ratio 8) were independent risk factors for postoperative death after LT.
The researchers suggest that SLKT might be a better choice for RIFLE stage 2 or 3 patients than LT alone.
Long-term outcomes of simultaneous liver-kidney transplant patients with Hepatitis B compared to liver transplant alone. Li H, Fan MQ, Men TY et al. Med Sci Monit. 2016 Feb 1;22:332-340
Novel HCV inhibitors interfere with viral entry
Novel benzothiazepinecarboxamide (BTC) inhibitors that interfere with early and late steps of the HCV viral life cycle have been identified.
Upon screening synthetic small molecule libraries with the infectious HCV cell culture system, researchers at the Korean Pasteur Institute identified a BTC scaffold that inhibits HCV. A structure-activity relationship (SAR) study with BTCs was performed, and modifications that led to nanomolar antiviral activity and improved the selective index (CC50/EC50) by more than 1,000-fold were identified. In addition, a pharmacophore modeling study determined that the tricyclic core and positive charge on the piperidine moiety were essential for antiviral activity.
Furthermore, the researchers demonstrated that BTC interferes with HCV glycoprotein E1/E2-mediated viral entry and the generation of infectious virions by using HCV pseudoparticle and cell culture supernatant transfer assays, respectively. BTC showed potent antiviral activity against HCV genotype 2 but was less potent against a genotype 1/2 chimeric virus, which expressed the structural proteins of HCV genotype 1.
Benzothiazepinecarboxamides: Novel hepatitis C virus inhibitors that interfere with viral entry and the generation of infectious virions. Kim HY, Kong S, Oh S et al. Antiviral Res. 2016 Feb 2 [Epub ahead of print]
Improved HCV outcomes with interferon/ribavirin-free regimens
In an analysis of studies, the use of interferon (IFN)- and ribavirin (RBV)-free regimens in older adults with HCV resulted in significant improvement of patient-reported outcomes (PROs).
Researchers at Inova Fairfax Hospital, Falls Church, USA, assessed the effect of different treatment regimens for chronic HCV on the PROs of patients aged 65 and older. PRO data from eight multinational phase two and three clinical trials were included.
Of 3,120 participants in these clinical trials, 229 had a mean age of 67.8. Of these, 75% were treatment-naïve, and 22% were cirrhotic. Ninety of these received ledipasvir plus sofosbuvir (LDV + SOF), 119 received SOF plus ribavirin (SOF + RBV), and 20 received pegylated IFN, SOF, and RBV (IFN + SOF + RBV).
The participants aged 65 and older had slightly more pretreatment PRO impairment in their physical functioning than younger individuals (-3.1% on a normalised 0-100% PRO scale).
Despite this, these participants experienced significant PRO improvement during treatment with IFN-free RBV-free regimens (up to +8.0%), similar to improvements in younger participants. In contrast, participants aged 65 and older experienced substantial decline in PROs while receiving IFN- or RBV-containing regimens (up to -18.9% in IFN + SOF + RBV, -10.4% in IFN-free SOF+RBV), and some were greater than in the younger group.
Nevertheless, after achieving sustained viral clearance at post-treatment week 12, PROs in participants aged 65 and older improved regardless of the regimen (up to +10.4%). In multivariate analysis of the cohort aged 65 and older, the use of IFN and RBV was consistently associated with PRO impairment during treatment.
Patient-reported outcomes of elderly adults with chronic Hepatitis C treated with interferon- and ribavirin-free regimens. Younossi ZM, Stepanova M, Nader F et al. J Am Geriatr Soc. 2016 Jan 30 [Epub ahead of print]
Short-term entecavir safe and effective in paediatric HBV
Entecavir in children and adolescents with chronic HBV is safe and shows clinical benefits in short-term biochemical and virologic responses, a new study concluded.
In the study, at the National Taiwan University Hospital, group one comprised nine treatment-naïve patients (median aged 12.2 years) who had been HBeAg seropositive for more than six months, and had alanine aminotransferase (ALT) of more than two times the upper limit of normal value (30 IU/L). They received entecavir at a dose of 0.015 mg/kg/d, with a maximal dose of 0.5 mg daily, for at least 52 weeks. Another 27 untreated chronic HBV patients matched for age, sex, ALT levels, and HBeAg status were recruited as the control group.
The entecavir-treated patients achieved rapid ALT normalisation (all before eight months of treatment) compared with the control group and had a greater chance of achieving undetectable HBV DNA levels at Week 52 after treatment (55.6% versus 11.1%).
The cumulative incidence rates of HBeAg seroconversion were similarly high in both groups (entecavir group 44% at one year and 78% at two years; control group 37% and 63%, respectively). The entecavir group also had a trend of better complete response than the control group (22.2% versus 0%). None of the entecavir-treated patients reported significant adverse effects.
Entecavir treatment in children and adolescents with chronic hepatitis B virus infection. Chang KC, Wu JF, Hsu HY et al. Pediatr Neonatol. 2015 Dec 23 [Epub ahead of print]
Tacrolimus plus entecavir improves remission of HBV-associated glomerulonephritis
Tacrolimus with entecavir was fast and effective at inducing remission of HBV-associated glomerulonephritis in adults, a Chinese study reported.
The study authors have suggested the two may have a synergistic antiviral effect used together.
In the study, at Guangdong General Hospital, 23 HBV patients with biopsy-proven membranous nephropathy received tacrolimus (0.05mg/kg/day) in combination with entecavir over 24 weeks, whereas 19 received entecavir monotherapy.
The probability of proteinuria remission in the combination group was 69% after 12 weeks and 87% after 24, while in the monotherapy group it was 26% and 42%, respectively.
The mean time to partial or complete remission was 18.6 weeks in the combination patients and 34.3 weeks in the monotherapy group. There was a decrease in the HBV DNA titre in all patients with active HBV replication. None of the HBV carriers in the combination group showed evidence of HBV reactivation. The serum creatinine and alanine aminotransferase levels remained stable in both groups. The tacrolimus target trough concentration was 5-10ng/ml.
The combination of tacrolimus and entecavir improves the remission of HBV-associated glomerulonephritis without enhancing viral replication. Wang L, Ye Z, Liang H et al. Clin Chim Acta. 2016 Jan 22 [Epub ahead of print]
Increasing prevalence of cirrhosis among US adults with HCV
The proportion of HCV-infected Americans with cirrhosis increased from 6.6% to 17.0% over the past two decades.
A new study found the prevalence of cirrhosis was highest among individuals who were unaware of their HCV infection.
Researchers at Stanford University School of Medicine used National Health and Nutrition Examination Survey (NHANES) data to identify adults with detectable serum HCV RNA. The prevalence of advanced fibrosis and cirrhosis was determined for Eras 1 (1988-94), 2 (1999-2006) and 3 (2007-12) by using FIB-4 > 3.25 and APRI > 2.0, respectively.
Out of 52,644 NHANES examinees, 49,429 were tested for HCV, of whom 725 met the inclusion criteria (positive HCV RNA with available data for FIB-4 and APRI). Based on APRI, 6.6% of HCV-infected adults in Era One, 7.6% in Era Two and 17.0% in Era Three had cirrhosis.
In the multivariable regression analysis, this era effect was attributable to increasing age (odds ratio 1.04), diabetes (odds ratio 2.33) and obesity (odds ratio 2.96). Cirrhosis was as common among respondents who were unaware of their infection as those who were aware (both 11%). Results were identical when FIB-4 was used.
The researchers say these data highlight the urgency for HCV screening regardless of symptoms, systematic assessment for liver fibrosis in those with HCV infection and institution of antivirals to prevent advanced liver disease.
Increasing prevalence of cirrhosis among US adults aware or unaware of their chronic hepatitis C virus infection. Udompap P, Mannalithara A, Heo N et al. J Hepatol. 2016 Jan 22 [Epub ahead of print]
Entecavir can be genotoxic
New genetic studies show that the anti-HBV nucleotide analogue, entecavir, has a genotoxic effect.
To evaluate its genotoxic mechanisms, researchers at Sichuan University, China, analysed the effect of entecavir on a panel of chicken DT40 B-lymphocyte isogenic mutant cell line deficient in DNA repair and damage tolerance pathways.
The results showed that Parp1-/- mutant cells defective in single-strand break (SSB) repair were the most sensitive to entecavir. Brca1-/-, Ubc13-/- and translesion-DNA-synthesis deficient cells including Rad18-/- and Rev3-/- were hypersensitive to entecavir.
XPA-/- mutant deficient in nucleotide excision repair was also slightly sensitive to entecavir. γ-H2AX foci forming assay confirmed the existence of DNA damage by entecavir in Parp1-/-, Rad18-/- and Brca1-/- mutants. Karyotype assay further showed entecavir-induced chromosomal aberrations, especially the chromosome gaps in Parp1-/-, Brca1-/-, Rad18-/- and Rev3-/- cells when compared with wild-type cells.
The researchers concluded these genetic comprehensive studies clearly identified the genotoxic potentials of entecavir and suggested that SSB and postreplication repair pathways may suppress entecavir-induced genotoxicity.
Genetic evidence for genotoxic effect of entecavir, an anti-hepatitis B virus nucleotide analogue. Jiang L, Wu X, He F et al. PLoS One. 2016 Jan 22;11(1):e0147440
Impaired glucose metabolism increases death risk in HCV patients with cirrhosis
In compensated HCV-related cirrhotic patients, diabetes and marked insulin resistance are independently associated with poorer overall survival.
A new multicentre study also found an increased risk of hepatic decompensation in these patients.
A total of 250 subjects in Australia, Cuba and Spain, with compensated HCV-related cirrhosis and without known diabetes, underwent an oral glucose tolerance test and were subsequently followed for a median 201 weeks.
At baseline, 67 had Type 2 diabetes. During follow-up, 28 deaths and 55 first events of decompensation occurred. After adjustment for potential confounding covariates, overall mortality/liver transplant (hazard ratio 2.2) and hepatic decompensation events (hazard ratio 1.9) were significantly higher in those with diabetes.
Patients with a HOMA-IR >5 showed higher rates of mortality (hazard ratio 2.2). The rates of hepatic decompensation were higher in patients with HOMA-IR >3 (hazard ratio 1.7).
Overall, two-hour plasma glucose was the most robust predictor of overall mortality (hazard ratio 2.5) and decompensation (hazard ratio 2.7).
Impaired glucose metabolism increases risk of hepatic decompensation and death in patients with compensated hepatitis C virus-related cirrhosis. Calzadilla-Bertot L, Vilar-Gomez E, Torres-Gonzalez A et al. Dig Liver Dis. 2015 Dec 25 [Epub ahead of print]
Alpha-fetoprotein as a biomarker for HCC in hepatitis patients
Two new studies demonstrate how alpha-fetoprotein (AFP) remains a valuable biomarker for predicting hepatocellular carcinoma (HCC) in hepatitis patients.
A Chinese study concluded that serum AFP was of diagnosis and prognostic predicting value for HCC with chronic HBV infection, and suggests its use as a biomarker in HBV endemic area like south east Asia (1).
Researchers from Peking University Health Science Centre studied 318 HBV patients, 731 cirrhosis patients and 796 HCC patients. Using 11.62ng/mL as a cut-off value, the positive rate of AFP test among serum HBsAg positive HCC patients was significantly higher than that in HBsAg negative HCC patients (79.55% versus 56.49%). Similarly, the median serum AFP level in HCC patients with serum HBsAg positive was significantly higher than that in those HBsAg negative HCC patients (423.89ng/ml versus 40.82ng/ml).
In addition, Kaplan-Meier curve analysis revealed that lower pre-operative AFP level implicated a much higher overall survival rate. Of note, such prognosis predicting value was only seen in those chronic HBV infection-related HCC patients, but not among the HCC patients aetiologically irrelevant to HBV infection.
A Brazilian study has suggested AFP could be used to distinguish between patients with HCC and cirrhosis or HCV, and that vascular endothelial growth factor (VEGF) could be a potential biomarker for HCC (2).
Researchers at Faculdade de Medicina de São José do Rio Preto evaluated the influence of the VEGF-C936T polymorphism on the prognosis of HCC, cirrhosis and HCV infection. A total of 285 subjects were studied: 68 HCC, 118 cirrhosis, 43 HCV, and 56 healthy controls.
The genotype CC (frequencies between 63.24% and 76.79%) and the C allele (absolute frequencies from 0.816 to 0.884) were prevalent in all groups. Higher VEGF levels in HCC patients (588.0 pg/mL) were observed, particularly in patients with the T allele in VEGF -C936T (764.4 pg/mL) compared to those in the other groups.
The same trend occurred with AFP levels (HCC 8.522; cirrhosis 12.7; HCV 4.6; control 2.7 ng/mL). Levels of VEGF and AFP showed sensitivity of 65% and 28% and specificity of 85 and 99%, respectively, for HCC patients.
1. Alpha-fetoprotein still is a valuable diagnostic and prognosis predicting biomarker in hepatitis B virus infection-related hepatocellular carcinoma. Yao M, Zhao J, Lu F. Oncotarget. 2016 Jan 13.[Epub ahead of print]
2. Influence of vascular endothelial growth factor and alpha-fetoprotein on hepatocellular carcinoma. Yvamoto EY, Ferreira RF, Nogueira V et al. Genet Mol Res. 2015 Dec 21;14(4):17453-62
Aspirin may protect against liver fibrosis in adults
Aspirin may play a role in the prevention and treatment of fibrosis among adults with suspected chronic liver diseases, a US study suggests.
The study, at Harvard Medical School, Boston, used data from the National Health and Nutrition Examination Survey III to identify 1,856 individuals with suspected chronic liver disease.
The use of aspirin was associated with a significantly lower composite liver fibrosis index calculated from FIB4, APRI, Forns and NFS. The association of aspirin with lower fibrosis scores was significantly larger among those with suspected chronic liver disease compared to those without. The negative association between aspirin use and lower fibrosis index was consistent across all four fibrosis indices in individuals with chronic viral hepatitis, suspected alcoholic liver disease and NASH. In comparison, no negative associations with liver fibrosis were seen with ibuprofen in parallel analyses.
The researchers suggest aspirin and other anti-platelet drugs warrant further investigation for the prevention and treatment of liver fibrosis.
Aspirin use is associated with lower indices of liver fibrosis among adults in the United States. Jiang ZG, Feldbrügge L, Tapper EB et al. Aliment Pharmacol Ther. 2016 Jan 7 [Epub ahead of print]
Low cardiovascular risk in children receiving liver transplants
Children receiving liver transplants (LTs) do not present with significant cardiovascular risk factors (CVRF), a new French study suggests.
Researchers at Lyon University retrospectively assessed CVRF, lipid abnormalities, and atherosclerosis (appraised by c-IMT) in 31 children who underwent LTs between 1990 and 2000. Their median age at LT was 14 months and the median follow-up after LT was 11.9 years.
In these children, obesity (9.7%) and treated hypertension (9.7%) were rare. None of the patients were smokers or diabetic. High TC and TG were both observed in 6.5%. The mean c-IMT for male patients was 1.22mm and for female patients,1.58 mm.
Seven patients (22%) had a mean c-IMT above +2 s.d. Values below the fifth percentile were noted for LDL-cholesterol (58.1%), HDL-cholesterol (25.8%), apolipoprotein B (40%), and apolipoprotein A1 (20%). LDL-cholesterol and apolipoprotein B levels were significantly lower in patients treated by tacrolimus in comparison with CsA (p < 0.05).
Lipid profile and cardiovascular risk factors in paediatric liver transplant recipients. Roblin E, Dumortier J, Di Filippo M et al. Pediatr Transplant. 2016 Jan 11 [Epub ahead of print]
Benefit of adding mericitabine to protease inhibitor regimens in HCVg1
Adding a nucleoside polymerase inhibitor with intermediate antiviral potency to regimens containing a first-generation protease inhibitor (PI) may benefit difficult-to-treat HCV g1 patients.
Two studies have demonstrated the approach increased sustained virological response (SVR) rates and reduced relapse rates in this group.
Researchers studied the incremental benefits associated with adding mericitabine (nucleoside analogue inhibitor of HCV polymerase) to a PI plus PegIFN alfa-2a/RBV-based therapy in two double-blind randomised multicentre phase two trials. DYNAMO 1 used boceprevir and DYNAMO 2, telaprevir.
Overall, the addition of mericitabine to PI plus PegIFN alfa-2a/RBV therapy resulted in SVR12 rates of 60% to 70% in DYNAMO 1 and of 71% to 96% in DYNAMO 2. SVR12 rates were similar in patients infected with HCV genotype 1a and 1b in both trials.
The placebo control arms in both studies were stopped because of high rates of virological failure. Numerically lower relapse rates were associated with longer treatment with mericitabine (24 versus 12 weeks), telaprevir-containing regimens, and regimens that included 48 weeks of PegIFN alfa-2a/RBV therapy. No mericitabine resistance mutations were identified in any patient in either trial.
Mericitabine and either boceprevir or telaprevir in combination with peginterferon alfa-2a plus ribavirin for patients with chronic hepatitis C genotype 1 infection and prior null response: the randomized DYNAMO 1 and DYNAMO 2 studies. Wedemeyer H, Forns X, Hézode C et al. PLoS One. 2016 Jan 11;11(1):e0145409
Higher rates of infections among HCV patients in a surgical intensive care unit
In a US surgical intensive care unit (SICU), patients with HCV had an increased incidence of infectious complications compared with non-HCV patients.
A total of 1,941 patients admitted to the SICU at Houston’s Baylor College of Medicine between 2008 and 2012 were studied. Those who were HCV-positive had a higher overall incidence of infectious complications (25% versus 18%), particularly ventilator-associated pneumonia (VAP) and bacteraemia. The increased incidences of VAP and bacteraemia persisted when cirrhotic patients were excluded.
Prolonged intubation (odds ratio 2.1), abdominal surgery (odds ratio 1.6), and model for end-stage liver disease ≥ 15 (odds ratio 1.4) were independent predictors of SICU infectious complications.
Hepatitis C status and infectious complications in the surgical intensive care unit: a retrospective analysis of 1,941 consecutive patients. Kueht M, Bebko S, Helmick R et al. Am J Surg. 2015 Dec 13 [Epub ahead of print]
Gender influences HCV outcomes
Gender influences fibrosis progression, likelihood of initiating HCV antiviral therapy, and treatment outcomes, a new Canadian study suggests.
Among 1,978 chronic HCV-infected patients followed at The Ottawa Hospital and Regional Viral Hepatitis Programme, 630 were women. Compared to the men, they who had lower weight as well as liver enzyme and HCV RNA levels.
They were more likely to have non-genotype-1, black or Asian, and immigrants from Africa and Asia. Women aged under 50, on average, had lower fibrosis scores than men. Beyond the age of 50 years, the mean fibrosis scores were similar, suggesting a “catch-up” phase.
Women were less likely to have initiated interferon-based HCV antiviral therapy. Their crude sustained virological responses (SVR) were higher, but, when determined by multivariable analysis, were similar to men (odds ratio 0.92).
Women of low socioeconomic status were more likely to be HIV co-infected and had higher rates of fibrosis progression. Women living in low-income neighbourhoods were less likely to achieve SVR (odds ratio 0.50) compared with women in higher income regions.
Influence of female sex on hepatitis C virus infection progression and treatment outcomes. Corsi DJ, Karges W, Thavorn K et al. Eur J Gastroenterol Hepatol. 2016 Jan 7. [Epub ahead of print]
Tenofovir fails to prevent HIV in men who have sex with men
The use of single agent, tenofovir disoproxil fumarate (TDF), failed to prevent HIV acquisition or the establishment of a viral reservoir in two men who have sex with men.
The World Health Organization recently recommended Truvada (tenofovir disoproxil/emtricitabine) or TDF for high-risk individuals, with limited data for single-agent TDF pre-exposure prophylaxis in men who have sex with men.
Researchers from Guys and St Thomas' NHS Trust, London, reported two cases of TDF pre-exposure prophylaxis failure in men who had sex with men and who had received long-term TDF for HBV infection and who had therapeutic levels of drug immediately after HIV acquisition.
Rapid antiretroviral intensification at the diagnosis of acute HIV infection failed to limit immune dysfunction or prevent the establishment of a viral reservoir.
Tenofovir disoproxil fumarate fails to prevent HIV acquisition or the establishment of a viral reservoir: two case reports. Fox J, Brady M, Alexander H et al. Infect Dis Ther. 2016 Jan 9. [Epub ahead of print]
Reduced prophylactic antiviral therapy in patients with DLBCL
Prophylactic antiviral therapy could be withdrawn six months after ending chemotherapy in HBsAg-negative/anti-HBc-positive patients with diffuse large B cell lymphoma (DLBCL).
This was the conclusion of researchers at Peking University Cancer Hospital and Institute who retrospectively analysed 107 newly diagnosed DLBCL patients with HBV who received chemotherapy.
The median time from the cessation of anti-tumor therapy to the withdrawal of prophylactic antiviral therapy was 6.1 months. The incidence of delayed HBV reactivation was 21.7% in the HBsAg-positive group and none in the HBsAg-negative/anti-HBc-positive group. No HBV-related fulminant hepatitis or hepatitis-related deaths occurred.
The multivariate analysis showed that female gender and more than eight cycles of chemotherapy were independent risk factors of HBV reactivation in HBsAg-positive patients.
The researchers suggest a longer course (i.e. over six months) of prophylactic antiviral drug administration may be an optimal option to prevent delayed HBV reactivation for HBsAg-positive patients.
Hepatitis B virus reactivation after withdrawal of prophylactic antiviral therapy in patients with diffuse large B cell lymphoma. Liu WP, Wang XP, Zheng W et al. Leuk Lymphoma. 2016 Jan 4:1-8. [Epub ahead of print]
Efficacy of second generation DAAs for treatment-naïve HCV g1B
Second generation direct-acting antiviral agents (DAAs) with pegylated interferon and ribavirin (PR) and dual DAA regimens should become first line treatments for naïve HCV genotype 1.
Authors from Mahidol University, Bangkok, have performed a literature review and network meta-analysis and concluded the DAAs offer significant clinical benefits over PR alone.
They compared the treatment efficacy of the second generation DAAs, simeprevir (SMV), sofosbuvir (SOF), daclatasvir (DCV), ledipasvir (LDV), and paritaprevir/ritonavir/ombitasvir plus dasabuvir (PrOD) for naïve HCV genotype 1. Primary outcomes were sustained virological response at weeks 12 (SVR12) and 24 (SVR24) after the end of treatment and adverse drug events. Sixteen studies were included in the analysis.
Compared with the PR regimen, SOF plus PR, SMV plus PR, and DVC plus PR regimens yielded significantly higher probability of SVR24 with pooled risk ratios of 1.98, 1.46 and 1.68, respectively.
Pooled incidence rates of SVR12 and SVR24 in all treatment regimens without PR (pooled incidence of SVR12 ranging from 93% to 100%, and pooled incidence of SVR24 ranging from 89% to 96%) were much higher than the pooled incidence rates of SVR12 (51%) and SVR24 (48%) in PR alone.
In comparing SOF plus LDV with ribavirin and SOF plus LDV without ribavirin, the chance of SVR12 was not significantly different between these two regimens, with the pooled risk ratio of 0.99.
The risks of serious adverse drug events, anaemia and fatigue were relatively higher in treatment regimens with PR than in the treatment regimens without PR.
Efficacy of second generation direct-acting antiviral agents for treatment naïve hepatitis C genotype 1: a systematic review and network meta-analysis. Suwanthawornkul T, Anothaisintawee T, Sobhonslidsuk A et al. PLoS One. 2015 Dec 31;10(12):e0145953
Increased glucose metabolism/insulin secretion in cirrhotic HBV patients
HBV patients with liver cirrhosis may be at an increased risk of insulin resistance and abnormal glucose metabolism, new evidence suggests.
In a study at China’s Affiliated Jiangyin Hospital of Southeast University Medical College, 106 HBV positive subjects with liver cirrhosis as well as with different grade of Child-Pugh and 37 healthy subjects had the oral glucose tolerance test (OGTT), C-peptide and insulin release test. Plasma glucose and insulin levels were analysed periodically for two hours after oral glucose loading.
There was no significant difference in the level of fasting plasma glucose and C-peptide between the two groups. However, the levels of OGTT two-hour glucose, insulin and C peptide were significantly higher in the cirrhosis group than in the controls.
The peak insulin and C-peptide response occurred at 60 minutes in the controls but was delayed to 120 minutes in the cirrhosis group. There was a significant difference between the two groups in the pattern of plasma glucose levels at corresponding time points. The OGTT two hour glucose and insulin levels were positively correlated with Child-Pugh Scores.
The investigation of glucose metabolism and insulin secretion in subjects of chronic hepatitis B with cirrhosis. Guo CH, Sun TT, Weng XD et al. Int J Clin Exp Pathol. 2015 Oct 1; 8(10): 13381-6
BASL welcomes new drinking guidelines
BASL has welcomed new Government guidelines, which state there is no safe level of drinking.
In a report published today (Friday, 8 January), the UK’s Chief Medical Officer warns any level of alcohol consumption increases the risk of a range of cancers. It also states men should have no more than 14 units a week, bringing the limit in line with the recommended maximum for women.
It says the oft-reported heart health benefits of alcohol only apply for women 55 and over, and concluded that there is no justification for drinking for health reasons. It also recommends pregnant women avoid alcohol altogether.
A BASL spokesman said it was an important report that enabled the public to make informed choices about the graduated risks of drinking alcohol.
“It tackles the increasingly tenuous myth that alcohol could be in any way beneficial for cardiovascular health, and reverses the unhelpful 'daily drinking' guideline in favour of a sensible weekly total - the equivalent of two bottles of wine shared with a partner plus a couple of pints at the weekend,” he added.
Dame Sally Davies, Chief Medical Officer for England, said any level of regular drinking carried a health risk, but sticking to the weekly limit would keep the risk of cancer and liver disease low.
“I want pregnant women to be very clear that they should avoid alcohol as a precaution. Although the risk of harm to the baby is low if they have drunk small amounts of alcohol before becoming aware of the pregnancy, there is no ‘safe’ level of alcohol to drink when you are pregnant,” she added.
“What we are aiming to do with these guidelines is give the public the latest and most up to date scientific information so that they can make informed decisions about their own drinking and the level of risk they are prepared to take.”
HCV g4 more common in black Africans in Belgium
In a Belgian study, patients with HCV genotype 4 (HCV-4) were more frequently of black African origin than of any other origin.
This multicentre study selected 473 HCV-4 patients from seven Belgian hospital databases and compared them according to ethnic origin, i.e., black African (331) or not (142), for epidemiological, clinical, biological and histological characteristics. Interleukin 28B polymorphism (CC-genotype) was evaluated in a second cohort of 69 black African and 30 non-black African patients.
Compared to other patients, the black African patients were more likely to be female and were older, commonly overweight, frequently had abnormal glucose metabolism and arterial hypertension. They were less likely to have dyslipidemia, a history of alcohol consumption or ALT elevation. The route of infection was more frequently unknown in these patients.
Black African patients had more HCV-4 subtypes, were less frequently of IL28B CC-genotype and had less severe liver fibrosis. The proportion of patients who received antiviral treatment was similar in the two groups.
Ethnic epidemiological profiles and antiviral therapy among patients infected with hepatitis C virus genotype 4: a multicentre study from Belgium. Nkuize M, Mulkay JP, Moreno C et al. Acta Gastroenterol Belg. 2015 Oct-Dec; 78(4):365-72
Chronic HBV with spontaneous severe acute exacerbation – a review
A new review summarises our current knowledge regarding chronic HBV with severe spontaneous acute exacerbation.
The reviewers, from Kaohsiung Veterans General Hospital in Taiwan, explain that spontaneous acute exacerbation is not uncommon in the natural history of chronic HBV, with a cumulative incidence of 10% to 30% every year. While exacerbations can be mild, some patients may develop hepatic decompensation and even die.
The underlying pathogenesis is possibly related to the activation of cytotoxic T lymphocyte-mediated immune response against HBV. An upsurge of serum HBV DNA usually precedes the rise of alanine aminotransferase and bilirubin.
Whether antiviral treatment can benefit in this condition remains controversial, early nucleos(t)ide analogue (NA) treatment seemed to be associated with an improved outcome. There has been no randomized study that has compared the effects of different NAs in this setting. However, potent NAs with good resistance profiles are recommended.
Chronic hepatitis B with spontaneous severe acute exacerbation. Tsai WL, Sun WC, Cheng JS. Int J Mol Sci. 2015 Nov 26; 16(12):28126-28145
Ledipasvir/sofosbuvir highly effective for older genotype 1 HCV patients
Ledipasvir/sofosbuvir (LDV/SOF), with or without ribavirin (RBV) has been shown to be highly effective for the treatment of genotype 1 chronic HCV in patients aged 65-plus.
Among 2,293 patients with genotype 1 chronic HCV enrolled in four multi-national phase three trials, 264 were aged 65 or older and 24 were over 75. All were treated with LDV/SOF, and 1,042 also received RBV.
Sustained virological response at 12 weeks (SVR12) was achieved by 97% of 2,029 patients aged under 65, and 98% of the 264 aged 65 or older.
The most common adverse events (AEs) in both LDV/SOF groups, occurring in ≥ 10% of subjects, were headache and fatigue. The rate of study discontinuation due to AE was similar in the two age cohorts. The addition of RBV increased the number of AEs, treatment-related AEs, and AEs leading to study drug modification/interruption, particularly among elderly subjects.
Safety and efficacy of ledipasvir/sofosbuvir for the treatment of genotype 1 hepatitis C in subjects aged 65 years or older. Saab S, Park SH, Mizokami M et al. Hepatology. 2015 Dec 24 [Epub ahead of print]
HEV genotype 3 viremia mainly presents in underlying chronic liver diseases
HEV genotype 3 (HEV-3) viremia mainly presents in patients with underlying chronic liver diseases or an impaired immune system, Dutch investigators reported.
The investigators, from the Erasmus MC, University Medical Centre Rotterdam studied 79 patients with HEV-3 infections diagnosed by means of quantitative real-time reverse transcription-polymerase chain reaction test (RT-PCR).
Sixty-one patients were immunocompromised. Three had only transient viremia, 43 cleared the infection within six months and 26 developed chronic infection. Five patients were lost to follow-up.
All patients developing chronic infection were immunocompromised. Overall, 13 patients within this cohort died. Three patients had pre-existent liver diseases and died of liver-related causes. Time between diagnosis and death was shorter for patients with pre-existent liver diseases
Twenty-eight per cent of patients on immunosuppressive medication achieved viral clearance after reducing the dose of immunosuppressive therapy. Thirty patients were treated with off-label ribavirin, of whom 25 demonstrated a sustained viral response was documented.
Hepatitis E virus genotype 3 infection in a tertiary referral centre in the Netherlands: Clinical relevance and impact on patient morbidity. Nijskens CM, Pas SD, Cornelissen J et al. J Clin Virol. 2015 Dec 2; 74:82-87 [Epub ahead of print]
HBV increases risk of osteoporosis
People with HBV are at an increased risk of osteoporosis, a new Taiwanese study shows.
Using a nationwide Longitudinal Health Insurance Database 2000, the study compared 36,146 adult HBV patients with 144,584 patients without advanced liver disease
Compared with the comparison cohort, the HBV patients had a higher risk of osteoporosis (adjusted hazard ratio 1.14) after adjusting for age, sex, frequency of medical visits, and comorbidities of diabetes, hypertension, hyperlipidemia, heart failure, cirrhosis, chronic kidney disease, thyroid diseases, medication of steroid, PPI, warfarin, aspirin, and oestrogen replacement therapy.
The HBV patients exhibited a 1.13-fold higher risk of developing osteoporosis, but the risk of osteoporotic fracture was comparable between patients with HBV and the comparison cohort (adjusted hazard ratio 1.20). The incidence of osteoporosis increased with the increment of age (age ≤ 49, adjusted hazard ratio 1; age 50-64, 5.67,age ≧ 65, 13.3) and coexisting cirrhosis (adjusted hazard ratio 1.62).
However, the osteoporosis risk contributed by HBV decreased with age and the age-specific risk analyses showed that patients with HBV exhibited the highest risk of osteoporosis than patients without HBV for the patients aged ≤49 (adjusted hazard ratio 1.42). Furthermore, the osteoporosis risk contributed by HBV decreased with the presence of comorbidities (adjusted hazard ratio 1.27 versus 1.04).
Association between chronic hepatitis B virus infection and risk of osteoporosis: a nationwide population-based study. Chen CH, Lin CL, Kao CH. Medicine (Baltimore). 2015 Dec; 94(50): e2276
A new predictive score for HCC associated with HCV
A new easy-to-use, non-invasive score can help predict patients with hepatocellular carcinoma (HCC) associated with HCV.
Researchers from three Egyptian universities measured α-1-acid glycoprotein (AGP) and C-reactive protein (CRP) in the serum of 53 HCC patients, 20 liver cirrhosis patients and 15 healthy individuals. Area under receiver operating characteristic curves (AUCs) was used to create a predictive score comprising AGP, CRP, alpha fetoprotein (AFP) and albumin. The diagnostic performances of score was determined and compared with AFP alone for the diagnosis of HCC.
The combination of AGP, albumin, CRP and AFP had AUC 0.92 and sensitivity 85% which was higher than AFP alone. The odds ratio of having HCC was 8.4 for AGP, 5.8 for CRP, 12.5 for AFP and 6.5 for albumin.
The score predicted HCC with an odds ratio of 50.6 for HCC. The AUC of score in HCC with single tumour, absent vascular invasion and CLIP score (0-1) were 0.9, 0.9, 0.82, respectively, compared with 0.71, 0.71, 0.68 respectively, for AFP.
An easy and useful noninvasive score based on α-1-acid glycoprotein and C-reactive protein for diagnosis of patients with hepatocellular carcinoma associated with hepatitis C virus infection. Omran MM, Emran TM, Farid K et al. J Immunoassay Immunochem. 2015 Dec 18. [Epub ahead of print]
Entecavir plus tenofovir superior to entecavir alone in HBV
New data suggest that the combination of entecavir (ETV) and tenofovir (TDF) is superior for HBV suppression and ALT normalisation in partial responders to ETV monotherapy.
This was a retrospective cohort study consisting of 86 consecutive treatment-naive, ETV 0.5mg partial responders who maintained ETV 0.5mg daily or switched to either ETV 1.0mg daily or ETV/TDF 0.5mg/300mg in three US hospitals between 2005 and 2012.
In all therapy groups, the majority of patients were HBV e antigen-positive and had similar baseline alanine aminotransferase (ALT) levels. However, baseline HBV DNA and HBV DNA at regimen switch points were lower in the ETV 0.5mg cohort compared with those switched to ETV 1.0mg or ETV/TDF, respectively. The ETV 0.5 mg cohort also had the shortest duration of ETV 0.5mg therapy before switch.
After the switch point, more patients on the combination achieved complete viral suppression (CVS) compared with those on either ETV monotherapy at months six, 12 and 18. Compared with the ETV monotherapy groups, the ETV/TDF group also had higher rates of ALT normalisation at the three time points.
The multivariate analyses,inclusive of baseline age and treatment duration on initial therapy with ETV 0.5mg, indicated that the ETV/TDF combination (hazard ratio 12.19) was independently and positively associated with CVS, whereas high HBV DNA levels at baseline (hazard ratio 0.77) and at switch point (hazard ratio 0.46) were negatively associated with CVS. ETV 1.0mg dose was not a predictor for CVS compared with ETV 0.5mg.
Alternative therapies for chronic hepatitis B patients with partial virological response to standard entecavir monotherapy. Chaung KT, O'Brien C, Ha NB et al. J Clin Gastroenterol. 2015 Dec 5. [Epub ahead of print]
High rise in HCV among men who have sex with men
The incidence of HCV infection in HIV-positive men who have sex with men (MSM) rose 18-fold between 1998 and 2011 in Switzerland.
In a new study of predominantly HIV-negative MSM, half the participants were aware of their HCV. However, high rates of unprotected anal intercourse (UAI) and of UAI without HIV serosorting were reported.
Between 2011 and 2012, trained health care professionals in southwest Switzerland invited individuals attending (1) MSM screening clinics and (2) indoor and outdoor meeting areas to complete an anonymous questionnaire. Consenting participants were rapid tested for HCV (OraQuick HCV Rapid Antibody Test).
Of 918 MSM approached, 654 agreed to participate, most of whom were enrolled via MSM screening clinics. Of 654 participants, 21 disclosed being HIV positive and 140 had unknown HIV status.
In the preceding 12 months, 357 participants reported UAI and 321 reported UAI with partners of different/unknown HIV status. Not HIV serosorting was reported more frequently among HIV-positive individuals (76%). Three hundred and two participants were aware of their HCV, awareness being higher among clinic than meeting area participants. One individual with a negative HIV test result 18 months previously was newly diagnosed as being HCV positive on rapid testing.
The study authors suggest that, given the increasing incidence of HCV amongst MSM, counselling should be offered regardless of HIV status, with testing offered to those at high risk.
Hepatitis C virus awareness among men who have sex with men in southwest Switzerland. Clerc O, Darling K, Calmy A et al. Sex Transm Dis. 2016 Jan; 43(1):44-48
HCV eradication leads to reduced portal pressure
Among chronic HCV-infected patients with advanced hepatic fibrosis, platelet counts improved following sustained viral response (SVR).
Also, the change in platelets correlated with the change in spleen size following antiviral therapy.
These were the findings of an international retrospective study and, say the researchers, their results suggest that HCV eradication leads to reduced portal pressure.
In the study, platelet counts and spleen sizes were recorded in chronic HBV patients with Ishak four to six fibrosis who started antiviral therapy between 1990 and 2003. Last measured platelet counts and spleen sizes were compared to their pre-treatment values (within six months prior to the start of therapy).
Amongst 464 patients, 353 had cirrhosis and 187 attained a SVR. Among patients with SVR, median platelet count, increased by 35 x109/L. In comparison, patients without SVR showed a median decline of 17 x109/L.
In a subgroup of 209 patients, median decrease in spleen size was 1.0 cm for patients with SVR, while median spleen size increased with 0.6 cm among those without SVR. The changes in spleen size and platelet count were significantly correlated.
Improvement of platelets after SVR among patients with chronic HCV infection and advanced hepatic fibrosis. van der Meer AJ, Maan R, Veldt BJ et al. J Gastroenterol Hepatol. 2015 Dec 8 [Epub ahead of print]
Successful treatment of HCV in renal transplant recipients with DAAs
HCV eradication with direct-acting antiviral agents (DAAs) has been found to be successful after kidney transplantation, with few treatment-related side effects.
Researchers at the University of Pennsylvania collected data from 20 consecutive kidney recipients treated with interferon-free regimens for HCV; 88% were infected with genotype 1 and 50% had biopsy-proven advanced hepatic fibrosis on their most recent liver biopsy preceding treatment; 60% had failed treatment pre-transplant with interferon-based therapy. DAA treatment was initiated a median of 888 days after renal transplantation.
All patients cleared the virus while on therapy and 100% achieved a sustained virologic response at 12 weeks after completion of DAA therapy. The most commonly used regimen was sofosbuvir 400 mg daily in combination with simeprevir 150 mg daily. However, four different treatment approaches were employed, with comparable results. The DAAs were well tolerated and less than half of patients required calcineurin inhibitor dose adjustment during treatment.
Successful treatment of Hepatitis C in renal transplant recipients with direct-acting antiviral agents. Sawinski D, Kaur N, Ajeti A et al. Am J Transplant. 2015 Nov 25 [Epub ahead of print]
Why some HCV patients relapse after DAAs
A new study has identified risk factors associated with HCV treatment failure after direct acting antivirals (DAAs) in patients with complex treatment histories.
Amongst 35 HCV mono-infected patients at Mount Sinai Medical Centre, New York who were treated with boceprevir (BOC) or telaprevir (TVR), eight subsequently relapsed and were treated with simeprevir (SMV) and sofosbuvir (SOF) ± ribavirin (RBV) for 12 weeks.
All eight patients had an end of treatment response, but later relapsed. All had previously failed PEG/RBV dual therapy at least once in addition to prior failure with triple therapy. Total number of times treated ranged from three to six. All eight had liver cirrhosis and seven had genotype 1a HCV. Seven had over 1 million IU/mL HCV RNA at the time of re-treatment.
The authors concluded that twelve weeks of SMV/SOF/RBV is insufficient in cirrhotics with high-titre genotype 1a HCV.
Re-re-treatment of hepatitis C virus: Eight patients who relapsed twice after direct-acting-antiviral drugs. Hartman J, Bichoupan K, Patel N et al. World J Gastroenterol. 2015 Nov 21;21(43):12430-8
Limited role for pentoxifylline in the treatment of alcoholic hepatitis
Pentoxifylline is a phosphodiesterase inhibitor with an anti-TNF effect and has been reported to reduce mortality and the incidence of hepatorenal syndrome in severe alcoholic hepatitis (AH). However, a review of recent evidence concludes that it has no clear beneficial effects in severe AH but could perhaps be used in patients with a contraindication to corticosteroids.
The reviewer, from Hospital Clínic, IDIBAPS, Barcelona, points out that corticosteroids are still the treatment recommended by clinical guidelines, pentoxifylline being the second-line option for non-responders to corticosteroids and for patients with contraindications.
Several studies, of distinct quality, have tested the efficacy of pentoxifylline in different scenarios. The conclusions of these studies are that pentoxifylline seems to improve survival in comparison to placebo but has lower efficacy than corticosteroids, with no improvement in survival when added to corticosteroids or in non-responders to steroid therapy.
The role of pentoxifylline in severe AH is even more doubtful after the results of a very recent controlled study that showed no beneficial effect on survival at one, three and 12 months of follow up, although a very recent network meta-analysis reported a beneficial effect of pentoxifylline alone or with corticosteroids on short-term survival.
Is there a role for pentoxifylline in the treatment of alcoholic hepatitis? Caballeria J. Gastroenterol Hepatol. 2015 Nov 14 [Epub ahead of print]
Liver viral load correlates with liver damage in chronic HBV
The results of a new study show a strong correlation between liver viral load and liver damage in patients with chronic HBV.
Researchers at Babol University of Medical Sciences, Iran, studied 30 patients with chronic anti-Hbe positive HBV, with liver enzymes two or more times the upper limit of normal and positive HBV DNA of any amount.
The mean age of the patients was 32 and 24 were males. Ten patients had HBV viral load levels less than 20000 IU/mL. There was a significant correlation between liver viral load levels with staging or grading of liver damage.
Relationship between hepatitis B DNA viral load in the liver and its histology in patients with chronic hepatitis B. Biazar T, Yahyapour Y, Hasanjani Roushan MR et al. Caspian J Intern Med. 2015 Fall;6(4):209-212
Nucleoside analogues prevent HBV transmission from father to infant
Nucleoside analogues are effective and safe for the prevention of vertical transmission of HBV from father to infant, a new study shows.
Researchers at the third Hospital Liver Disease Centre of Qinhuangdao, China, studied 201 patients who were positive for HBV surface antigen (HBsAg), HBeAg, anti-HBc, and HBV DNA; of these, 189 had abnormal liver function. In all couples, the fathers were HBV DNA-negative and had normal liver function, and the mothers were anti-HB-positive before pregnancy. The control group comprised of 188 couples that visited the hospital during the same time period. The fathers in the control group were positive for HBsAg, HBeAg, anti-HBc, and HBV DNA. The mothers were HBsAg-negative and anti-HBs-positive.
No infants in the case group were HBsAg-positive and HBV DNA-positive, and all were anti-HBs-positive, indicating that father to infant HBV vertical transmission was prevented in the case group.
In the control group, 147 of 188 newborns were anti-HBs-positive at birth, 28 were HBV DNA-positive, and 19 were HBsAg-positive. A significant difference was observed between the two groups. No statistically significant difference was observed in the gestational age, birth weight, birth length, one-minute and eight-minute Apgar score. Nor in jaundice, other internal and surgical diseases, delivery mode, and other birth information between the neonates born to couples in the case and control groups; there were no foetal malformations and stillbirths in the two groups.
Efficacy and safety of nucleoside analogues in preventing vertical transmission of the hepatitis B virus from father to infant. Cao LH, Zhao PL, Liu ZM et al. Genet Mol Res. 2015 Dec 2;14(4):15539-46
Efficacy of nucleotide/nucleoside analogues in HBV-associated glomerulonephritis
A new meta-analysis of studies shows the efficacy of nucleotide/nucleoside analogue (NA) monotherapy for treating HBV-associated glomerulonephritis (HBV-GN).
Researchers found ten trials involving 325 patients – four randomised controlled trials, two cohort clinical trials, and four self-controlled studies.
Based on the fixed-effects model, the reviewers found significant proteinuria remission rate improvement in the NA group (relative risk 3.60), a negative conversion rate of HBV-DNA (relative risk 2.20), and clearance of HBeAg (relative risk 4.49).
Improvement in ALT (mean difference 56.60) was found with the fixed effects model, and a slight decrease in serum creatinine (mean difference 25.25) was shown.
Meta-analysis of the efficacy and safety of nucleotide/nucleoside analog monotherapy for hepatitis B virus-associated glomerulonephritis. Wang WN, Wu MY, Ma FZ, et al. Clin Nephrol. 2015 Dec 4. [Epub ahead of print]
HCV patients with high healthcare resource utilisation have more comorbidities
New data shows chronic HCV patients with high healthcare resource utilisation (HRU) have a high level of comorbidity at baseline, it also suggests non-HCV comorbidities and conditions are strong predictors of high HRU.
Using North American health insurance claims for 2001-2013, researchers studied 4,898 adult patients with two or more chronic HCV claims and six or more months of continuous insurance coverage before and more than 36 months after the first diagnosis.
Liver disease severity and both chronic HCV and non-HCV-related comorbidities and conditions were strong predictors of high healthcare costs, with odds ratios for ≥2 chronic HCV and ≥2 non-chronic HCV-related comorbidities/conditions 2.78 and 2.19, respectively.
Chronic-HCV and non-chronic HCV-related comorbidities and conditions were also strong predictors of liver disease progression with odds ratios for ≥2 chronic HCV-related and ≥2 non-chronic HCV-related comorbidities and conditions of 2.18 and 1.50, respectively.
Predictors of high healthcare resource utilization and liver disease progression among patients with chronic hepatitis C. LaMori J, Tandon N, Laliberté F et al. J Med Econ. 2015 Dec 1:1-31. [Epub ahead of print]
High risk of drug-drug interactions with new direct acting antivirals
Researchers have warned a significant number of HCV patients are at risk for drug-drug interactions (DDIs) if treated with the recently approved direct acting antivirals (DAAs).
Researchers from Hannover Medical School and the University of Liverpool, studied 261 HCV monoinfected patients who received DAA therapy at two intervals between 2011 and 2014. The potential for DDI between all these drugs and sofosbuvir/ribavirin, ledipasvir/sofosbuvir, sofosbuvir/daclatasvir,sofosbuvir/simeprevir, ombitasvir/paritaprevir/ritonavir±dasabuvir as well as boceprevir and telaprevir triple therapy was assessed using www.hep-druginteractions.org and the relevant prescribing information.
The 261 patients took a median number of two drugs and 20% did not take any medication. Sofosbuvir/ribavirin had the lowest risk to cause a potentially significant DDI (9.6%). In contrast, for ombitasvir/paritaprevir/ritonavir±dasabuvir, potentially significant DDI could be expected in 66.3% of the patients. Significant DDI for sofosbuvir/simeprevir would be expected in 31.4%, for sofosbuvir/daclatasvir in 36.8% and sofosbuvir/ledipasvir in 40.2%.
Proton pump inhibitors, thyroid hormones and dihydropyridine derivatives were frequently used and presented a risk of interacting with the antiviral regimen.
Drug-drug interactions with novel all oral interferon free antiviral agents in a large real-world cohort. Höner Zu Siederdissen C, Maasoumy B, Marra F et al. Clin Infect Dis. 2015 Nov 26 [Epub ahead of print]
Daclatasvir plus asunaprevir improves renal dysfunction in HCV
Clinicians have concluded the combination of daclatasvir and asunaprevir is safe for chronic HCV patients with renal dysfunction.
The clinicians, at Hiroshima University, treated a patient with HCV-related liver cirrhosis with severe leg oedema due to chronic renal dysfunction using this dual oral therapy.
Although serum ALT increased rapidly during the first week of treatment, the antiviral therapy was able to continue and liver function recovered spontaneously. After one month of treatment, serum HCV RNA became continuously undetectable, and serum albumin level gradually increased.
Throughout the therapy, serum creatinine level nearly normalised, and leg oedema gradually improved. These improvements continued after the combination therapy was completed. HCV RNA remained undetectable following the end of therapy, and sustained virological response at 12 weeks was achieved.
Improvement of renal dysfunction in a patient with HCV-related liver cirrhosis by daclatasvir and asunaprevir combination therapy: A case report. Tsuge M, Hiramatsu A, Shinohara F et al. Hepatol Res. 2015 Nov 27 [Epub ahead of print]
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