Hepatitis Research Today is a free monthly online journal that collates and summarizes the latest research about Hepatitis, including details on hepatitis a, b, c, causes, symptoms.

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

Everson GT, Hoefs JC, Seeff LB, Bonkovsky HL, Naishadham D, Shiffman ML, Kahn JA, Lok AS, Di Bisceglie AM, Lee WM, Dienstag JL, Ghany MG, Morishima C,

Section of Hepatology, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Denver, CO, USA. greg.everson@uchsc.edu

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.

Published 4 December 2006 in Hepatology, 44(6): 1675-84.
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