[1, 2] The effectiveness of antiviral treatment has historically been evaluated by the surrogate endpoint of sustained virologic response (SVR) 24 weeks after cessation of antiviral medication. In numerous studies, SVR has been associated with a reduced occurrence of liver failure, hepatocellular carcinoma (HCC), and liver-related deaths in patients with HCV.[3, 4] Whether the beneficial effects of SVR also result in reduced all-cause mortality, however, is the Ponatinib more essential

question to answer. Because all-cause mortality is the most definite clinical endpoint with clear interpretation, demonstrating direct clinical benefits of SVR on all-cause mortality would better justify the use of intensive and costly antiviral therapy. Knowing the effect of HCV antiviral treatment on all-cause mortality is also important for considering broader clinical questions such as the utility of birth cohort screening for HCV. In the largest prior effort, a study of 16,864 U.S. Veterans analyzed separately Stem Cell Compound Library clinical trial by genotype found reduced

all-cause mortality among patients with HCV genotypes 1, 2, and 3 who were treated in routine medical practice.[5] Because the majority of these patients were treated without liver biopsy, there was limited information about the impact of SVR on all-cause mortality in patients with severe fibrosis or cirrhosis. The current article by van der Meer et al.[6] seeks to add to the information about the impact of SVR on all-cause mortality, 上海皓元 particularly in patients with severe fibrosis or cirrhosis. Van der Meer et al. report on long-term outcomes from 530 patients from five large tertiary care hospitals in Europe and Canada. The patients started an interferon-based regimen between 1990 and 2003 following histologic proof of advanced hepatic fibrosis or cirrhosis (Ishak

score of 4 in 27% of patients, Ishak score of 5 in 19% and Ishak score of 6 in 54%). In all, 175 patients started interferon monotherapy, 148 patients started interferon/ribavirin, and 176 patients started pegylated interferon/ribavirin with resulting SVR rates of 5.1%, 23.6%, and 42.1%, respectively. An additional 14 patients started pegylated interferon monotherapy and 17 patients started consensus interferon with or without ribavirin. A total of 204 patients with initial non-SVR were retreated, of whom 67 subsequently achieved SVR. Ultimately, 192 of 530 patients (36%) achieved SVR. The patients with successful retreatment were considered as patients without SVR in the analysis until after successful treatment, at which point they were treated as patients with SVR for the remainder of the follow-up. Thirteen patients with SVR and 100 patients without SVR died (10-year cumulative all-cause mortality rate 8.9% [95% confidence interval (CI) 3.3%-14.5%] with SVR and 26.0% [95% CI 20.2%-28.