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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 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]
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]
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 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
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]
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]
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
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
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]