Impact of disease severity on outcome of antiviral therapy for chronic hepatitis C: Lessons from the HALT-C trial

In patients with chronic hepatitis C, advanced fibrosis and cirrhosis are associated with lower rates of sustained virologic response (SVR) to interferon (IFN)-based therapy. In this study, we assessed virologic response to retreatment with peginterferon alfa-2a and ribavirin (RBV), as a function of the baseline fibrosis score (Ishak staging) and platelet count, in 1,046 patients enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. All patients had failed prior treatment with IFN or peginterferon ± RBV and had Ishak fibrosis scores ≥ 3. Four groups of patients with increasingly severe liver disease were compared: (A) bridging fibrosis (Ishak 3 and 4) with platelet counts >125,000/mm 3 (n = 559); (B) bridging fibrosis with platelet counts ≤125,000/mm 3 (n = 96); (C) cirrhosis (Ishak 5 and 6) with platelet counts >125,000/mm 3 (n = 198); and (D) cirrhosis with platelet counts ≤125,000/mm 3 (n = 193). SVR rates were 23%, 17%, 10%, and 9% in groups A, B, C, and D, respectively ( P < .0001 for trend). Reduction in SVR as a function of increasingly severe disease was independent of age, percent African American, HCV genotype, HCV level, and type of prior therapy. Dose reduction lowered SVR frequencies, but to a lesser extent than disease severity. By logistic regression, cirrhosis ( P < .0001) was the major determinant that impaired virologic response, independent of dose reduction or platelet count. In conclusion , disease severity is a major independent determinant of rate of SVR in patients with advanced chronic hepatitis C. New strategies are needed to optimize antiviral therapy in these “difficult-to-cure” patients. (H EPATOLOGY 2006;44:1675–1684.)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55880/1/21440_ftp.pd