The neglected hepatitis C virus genotypes 4, 5 and 6: an international consensus report

Hepatitis C virus (HCV) genotypes 4, 5 and 6 represent >20% of all HCV cases worldwide. HCV-4 is mainly seen in Egypt, where it represents 90% of all HCV cases. Antischistosomal therapy was the main cause of contamination there, followed by procedures performed by informal providers and traditional healers such as dental care, wound treatment, circumcision, deliveries, excision and scarification. It is also highly prevalent in sub-Saharan Africa and in the Middle East. In Europe, its prevalence has recently increased particularly among intravenous drug users and in immigrants. HCV-5 is mainly found in South Africa, where it represents 40% of all HCV genotypes, but four pockets of HCV-5 were found in France, Spain, Syria and Belgium and sporadic cases were found elsewhere. The mode of transmission is mainly iatrogenic and transfusion. HCV-6 is found in Hong Kong, Vietnam, Thailand and Myanmar and also in American and Australian from Asian origin. The response to treatment in HCV-4 is intermediate between HCV-1 and HCV-2 and HCV-3. A sustained viral response is achieved in 43-70% with pegylated interferon and ribavirin. It is higher in Egyptians than Europeans and Africans and is negatively related to insulin resistance and to the severity of fibrosis. It increases to >80% with 24 weeks of therapy only if a rapid virological response is achieved. In HCV-5, a sustained virological response is achieved in >60% with 48 weeks of therapy. HCV-6 is also considered an easy-to-treat genotype, leading to a response in 60-85% of cases. © 2009 John Wiley & Sons A/S.link_to_subscribed_fulltex

Changes in anti-viral effectiveness of interferon after dose reduction in chronic hepatitis c patients: a case control study

BACKGROUND: High dose interferon induction treatment of hepatitis C viral infection blocks viral production over 95%. Since dose reduction is often performed due to clinical considerations, the effect of dose reduction on hepatitis C virus kinetics was studied. METHODS: A new model that allowed longitudinal changes in the parameters of viral dynamics was used in a group of genotype-1 patients (N = 15) with dose reduction from 10 to 3 million units of interferon daily in combination with ribavirin, in comparison to a control group (N = 9) with no dose reduction. RESULTS: Dose reduction gave rise to a complex viral kinetic pattern, which could be only explained by a decrease in interferon effectiveness in blocking virion production. The benefit of the rapid initial viral decline following the high induction dose is lost after dose reduction. In addition, in some patients also the second phase viral decline slope, which is highly predictive of success of treatment, was impaired by the dose reduction resulting in smaller percentage of viral clearance in the dose reduction group. CONCLUSIONS: These findings, while explaining the failure of many induction schedules, suggest that for genotype-1 patients induction therapy should be continued till HCVRNA negativity in serum in order to increase the sustained response rate for chronic hepatitis C

Liver cancer risk, coffee, and hepatitis C virus infection: a nested case–control study in Japan

We examined hepatocellular carcinoma mortality in relation to coffee consumption and anti-hepatitis C virus (HCV) antibody seropositivity in a nested case–control study involving 96 cases. The multivariate-adjusted odds ratios (95% confidence interval) for daily coffee drinkers vs non-drinkers were 0.49 (0.25–0.96), 0.31 (0.11–0.85), and 0.75 (0.29–1.92) in all cases, in HCV-positive and in HCV-negative individuals, respectively

Bayes Factors for Mixed Models: a Discussion

van Doorn et al. (2021) outlined various questions that arise when conducting Bayesian model comparison for mixed effects models. Seven response articles offered their own perspective on the preferred setup for mixed model comparison, on the most appropriate specification of prior distributions, and on the desirability of default recommendations. This article presents a round-table discussion that aims to clarify outstanding issues, explore common ground, and outline practical considerations for any researcher wishing to conduct a Bayesian mixed effects model comparison

Mortality rate of patients with asymptomatic primary biliary cirrhosis diagnosed at age 55 years or older is similar to that of the general population

Recent routine testing for liver function and anti-mitochondrial antibodies has increased the number of newly diagnosed patients with primary biliary cirrhosis (PBC). This study investigated the prognosis of asymptomatic PBC patients, focusing on age difference, to clarify its effect on the prognosis of PBC patients. The study was a systematic cohort analysis of 308 consecutive patients diagnosed with asymptomatic PBC. We compared prognosis between the elderly (55 years or older at the time of diagnosis) and the young patients (< 55 years). The mortality rate of the patients was also compared with that of an age- and gender-matched general population. The elderly patients showed a higher aspartate aminotransferase-to-platelet ratio, and lower alanine aminotransferase level than the young patients (P < 0.01 and P = 0.03, respectively). The two groups showed similar values for alkaline phosphatase and immunoglobulin M. Death in the young patients was more likely to be due to liver failure (71%), while the elderly were likely to die from other causes before the occurrence of liver failure (88%; P < 0.01), especially from malignancies (35%). The mortality rate of the elderly patients was not different from that of the age- and gender-matched general population (standardized mortality ratio, 1.1; 95% confidence interval, 0.6-1.7), although this rate was significantly higher than that of the young patients (P = 0.044). PBC often presents as more advanced disease in elderly patients than in the young. However, the mortality rate of the elderly patients is not different from that of an age- and gender-matched general population

Role of Sleep Disturbance in Chronic Hepatitis C Infection

Chronic infection with the hepatitis C virus (CHC) is associated with physical and mental symptoms including fatigue and depression that adversely affect quality of life. A related complaint, sleep disturbance, has received little attention in the literature, with the exception of sleep changes noted in cirrhosis and end-stage liver disease. We present an overview of studies indicating sleep problems in patients with CHC, with about 60% to 65% of individuals reporting such complaints. Evidence suggests that impairments in sleep quality exist independent of antiviral therapy with interferon-α and prior to advanced stages of liver disease. Further investigation of sleep disturbance in CHC patients with a mild stage of liver disease may provide important information on disease course as well as allow additional opportunities for patient support

Risk factors for hepatitis C virus infection among blood donors in southern Brazil: a case-control study

BACKGROUND: In Brazil, it is estimated that between 2.5 and 4.9% of the general population present anti-hepatitis C virus (HCV) antibodies, which corresponds to as many as 3.9 to 7.6 million chronic carriers. Chronic liver disease is associated with HCV infection in 20% to 58% of the Brazilian patients. The objective of this case-control study was to investigate the risk factors for presence of anti-HCV antibody in blood donors in southern Brazil. METHODS: One hundred and seventy eight blood donors with two positive ELISA results for anti-HCV were cases, and 356 controls tested negative. A standardized questionnaire was used to collect data concerning demographic and socioeconomic aspects, history of previous hepatitis infection, social and sexual behaviors, and number of donations. Variables were grouped into sets of hierarchical categories. Cases and controls were compared using logistic regression, odds ratios, and 95% confidence intervals. The statistical significance of the associations was assessed through likelihood ratio tests based on a P value < 0.05. RESULTS: The prevalence of anti-HCV among blood donors was 1.1%. Most of the donors were white and males. In the multivariate analysis, independent predictors of anti-HCV positivity were: intravenous drug use, blood transfusion >10 years earlier, having had two to four sexually transmitted diseases, incarceration, tattooing, sex with a hepatitis B or C virus carrier or with intravenous drug users. CONCLUSION: Intravenous drug use, blood transfusion, and tattooing were the main risk factors for anti-HCV positivity among blood donors from southern Brazil, but sexual HCV transmission should also be considered

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure. Affected individuals are usually in their fifth to seventh decades of life at time of diagnosis, and 90% are women. Annual incidence is estimated between 0.7 and 49 cases per million-population and prevalence between 6.7 and 940 cases per million-population (depending on age and sex). The majority of patients are asymptomatic at diagnosis, however, some patients present with symptoms of fatigue and/or pruritus. Patients may even present with ascites, hepatic encephalopathy and/or esophageal variceal hemorrhage. PBC is associated with other autoimmune diseases such as Sjogren's syndrome, scleroderma, Raynaud's phenomenon and CREST syndrome and is regarded as an organ specific autoimmune disease. Genetic susceptibility as a predisposing factor for PBC has been suggested. Environmental factors may have potential causative role (infection, chemicals, smoking). Diagnosis is based on a combination of clinical features, abnormal liver biochemical pattern in a cholestatic picture persisting for more than six months and presence of detectable antimitochondrial antibodies (AMA) in serum. All AMA negative patients with cholestatic liver disease should be carefully evaluated with cholangiography and liver biopsy. Ursodeoxycholic acid (UDCA) is the only currently known medication that can slow the disease progression. Patients, particularly those who start UDCA treatment at early-stage disease and who respond in terms of improvement of the liver biochemistry, have a good prognosis. Liver transplantation is usually an option for patients with liver failure and the outcome is 70% survival at 7 years. Recently, animal models have been discovered that may provide a new insight into the pathogenesis of this disease and facilitate appreciation for novel treatment in PBC