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

Abstract

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 > or = 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 < or =125,000/mm3 (n = 96); (C) cirrhosis (Ishak 5 and 6) with platelet counts >125,000/mm3 (n = 198); and (D) cirrhosis with platelet counts < or =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.

• Authors: 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, HALT-C Trial Group
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 44 Issue 6 Pg. 1675-84 (Dec 2006) ISSN: 0270-9139 [Print] United States
• PMID: 17133499 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Antiviral Agents
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• peginterferon alfa-2a

Topics

• Antiviral Agents (therapeutic use)
• Biopsy
• Drug Therapy, Combination
• Female
• Hepatitis C, Chronic (drug therapy, pathology)
• Humans
• Interferon alpha-2
• Interferon-alpha (therapeutic use)
• Liver (pathology)
• Liver Cirrhosis (drug therapy)
• Male
• Middle Aged
• Polyethylene Glycols (therapeutic use)
• Recombinant Proteins
• Ribavirin (adverse effects, therapeutic use)
• Treatment Failure
• Treatment Outcome