title: 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.affiliation: Section of Hepatology, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Denver, CO, USA. greg.everson@uchsc.edu
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Everson
authors.forename: John C
authors.initials: JC
authors.lastname: Hoefs
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Seeff
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
authors.forename: Deepa
authors.initials: D
authors.lastname: Naishadham
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kahn
authors.forename: Anna S F
authors.initials: AS
authors.lastname: Lok
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Di Bisceglie
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.forename: Jules L
authors.initials: JL
authors.lastname: Dienstag
authors.forename: Marc G
authors.initials: MG
authors.lastname: Ghany
authors.forename: Chihiro
authors.initials: C
authors.lastname: Morishima
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a