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

✍ Scribed by Gregory T. Everson; John C. Hoefs; Leonard B. Seeff; Herbert L. Bonkovsky; Deepa Naishadham; Mitchell L. Shiffman; Jeffrey A. Kahn; Anna S. F. Lok; Adrian M. Di Bisceglie; William M. Lee; Jules L. Dienstag; Marc G. Ghany; Chihiro Morishima

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 352 KB
• Volume: 44
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.21440

✦ Synopsis

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. (HEPATOLOGY 2006;44:1675-1684.