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

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

Research output: Contribution to journalArticle

135 Scopus citations


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/mm3 (n = 559); (B) bridging fibrosis with platelet counts ≤125,000/mm3 (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/mm3 (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.

Original languageEnglish (US)
Pages (from-to)1675-1684
Number of pages10
Issue number6
Publication statusPublished - Dec 2006


ASJC Scopus subject areas

  • Hepatology

Cite this

Everson, G. T., Hoefs, J. C., Seeff, L. B., Bonkovsky, H. L., Naishadham, D., Shiffman, M. L., ... Morishima, C. (2006). Impact of disease severity on outcome of antiviral therapy for chronic hepatitis C: Lessons from the HALT-C trial. Hepatology, 44(6), 1675-1684.