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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]
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]
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]
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]
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]
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]
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]
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.
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]
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]