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 > 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.) Abbreviations: HCV, hepatitis C virus; RBV, ribavirin; SVR, sustained virologic response; PEG-IFN, pegylated interferon; INR, international normalized ratio. From the:

Pegylated interferon-based treatment in patients with advanced liver disease due to chronic delta hepatitis

“…This is in variance with studies performed in CHC (27)(28)(29). In contrast, studies in CHB have reported both favorable (16) and unfavorable results (30 However, clinically important adverse events occurred in patients with advanced liver disease, which included two cases of hepatic decompensation and one case of tuberculosis reactivation.…”

British HIV Association guidelines for the management of coinfection with HIV‐1 and hepatitis B or C virus 2010

“…The National Institutes of Health (NIH)-sponsored Hepatitis C Antiviral Long-Term Treatment aganist Cirrhosis (HALT-C) clinical trial failed to show a benefit of maintenance interferon on differences in the rates of mortality, decompensation, HCC, or fibrosis progression between the peginterferon alpha-2a maintenance group and the control group [220]. A similar study in HIVpositive individuals -the SLAM-C study -was also unable to show any beneficial effect on fibrosis progression rates [221].…”

Hepatitis C viral kinetics in special populations

“…Thus, theoretically, patients with a high fraction of HCV-infected hepatocytes will have high ε c and hence will have a poorer chance of achieving SVR. Interestingly, Pal et al [47] showed that advanced liver disease is associated with a higher fraction of HCV-infected hepatocytes and lower SVR rates (<29%) than for patients without liver disease [25,26,48,49].…”