Peginterferon ALPHA-2A (40KD) Plus Ribavirin for the Treatment of Patients With Chronic Hepatitis C (CHC) and Compensated Liver Cirrhosis in Japan

Abstract

Introduction: Known predictors of response to combination pegylated interferon (PEG-IFN) and ribavirin (RBV) for treatment of chronic hepatitis C (CHC) include genotype, race, rapid virologic response, early virologic response and recently identified interleukin-28B polymorphism. There has been conflicting data regarding the relationship between weight loss during antiviral therapy and sustained virologic response (SVR). Purpose: To determine if weight loss during antiviral therapy correlates with SVR to PEG-IFN and RBV therapy in CHC patients. Methods: We conducted a retrospective chart review of approximately 500 randomly selected CHC patients treated with combination PEG-IFN and RBV therapy from 2004 to 2009 in our urban academic hepatology practice. Random selection was accomplished by electronically randomizing an alphabetical list of CHC patients seen in our practice. Patients with acute HCV infection, HBV or HIV co-infection, liver transplant recipients, patients on experimental protocols or extended treatment courses, with unavailable weight data or lost to follow up were excluded. Both treatment-naive and treatment-experienced patients were included. Univariate and multivariate analysis, including chi-square testing, t-test and logistic regression modeling using SAS 9.2, was completed to assess for association between weight loss and achieving SVR. Results: Data on 194 patients (68% genotype 1; 43% with advanced fibrosis) were analyzed after exclusion criteria applied. 37% of patients had SVR (including treatment-naive and prior non-responders and relapsers). Baseline characteristics for SVR and non-SVR groups were similar except for genotype (40% in SVR group were genotype 1 vs 84% in non-SVR group) and fibrosis scores (SVR group had lower scores). Overall, 68% had weight loss >1 kg, with 40% SVR in those with weight loss vs 24% SVR among those with no weight loss. Overall, the majority of weight loss (67%) occurred in the first 12 weeks, but for those with weight loss >10kg (10% of patients), only 40% of weight loss occurred by week 12. In multivariate analysis, weight loss > 5kg (28% of patients) was associated with SVR (aOR 2.9, CI 1.04-8.30). Consistent with previous studies, genotypes 2/3 (aOR 7.1, CI 2.94-17.28), lower stage of fibrosis (aOR 1.7, CI 1.162.44) and lower baseline weight (aOR 1.03, CI 1.01-1.06) were also associated with SVR. Conclusions: Our study found an association between SVR and weight loss while controlling for other known predictors of SVR. Our data suggests that weight trend during treatment of CHC patients with combination PEG-IFN and RBV should be monitored as weight loss may be used as a surrogate marker of SVR to the current standard of care.