Maintenance peginterferon therapy and other factors associated with hepatocellular carcinoma in patients with advanced hepatitis C

Anna S. Lok, James E. Everhart, Elizabeth C. Wright, Adrian M. Di Bisceglie, Haeyoung Kim, Richard K. Sterling, Gregory T. Everson, Karen L. Lindsay, William M. Lee, Herbert L. Bonkovsky, Jules L. Dienstag, Marc G. Ghany, Chihiro Morishima, Timothy R. Morgan

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149 Scopus citations

Abstract

Background & Aims: Interferon reportedly decreases the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial showed that 4 years of maintenance therapy with pegylated interferon (peginterferon) does not reduce liver disease progression. We investigated whether peginterferon decreases the incidence of HCC in the HALT-C cohort over a longer posttreatment follow-up period. Methods: The study included 1048 patients with chronic hepatitis C (Ishak fibrosis scores <3) who did not have a sustained virologic response (SVR) to therapy. They were randomly assigned to groups given a half-dose of peginterferon or no treatment (controls) for 3.5 years and followed up for a median of 6.1 (maximum, 8.7) years. Results: Eighty-eight patients developed HCC (68 definite, 20 presumed): 37 of 515 who were given peginterferon (7.2%) and 51 of 533 controls (9.6%; P = .24). There was a significantly lower incidence of HCC among patients given peginterferon therapy who had cirrhosis, but not fibrosis, based on analysis of baseline biopsy samples. After 7 years, the cumulative incidences of HCC in treated and control patients with cirrhosis were 7.8% and 24.2%, respectively (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.240.83); in treated and control patients with fibrosis, incidences were 8.3% and 6.8%, respectively (HR, 1.44; 95% CI, 0.772.69). Treated patients with a <2-point decrease in the histologic activity index, based on a follow-up biopsy, had a lower incidence of HCC than those with unchanged or increased scores (2.9% vs 9.4%; P = .03). Conclusions: Extended analysis of the HALT-C cohort showed that long-term peginterferon therapy does not reduce the incidence of HCC among patients with advanced hepatitis C who did not achieve SVRs. Patients with cirrhosis who received peginterferon treatment had a lower risk of HCC than controls.

Original languageEnglish (US)
Pages (from-to)840-849.e1
JournalGastroenterology
Volume140
Issue number3
DOIs
StatePublished - Mar 2011

Keywords

  • Hepatitis C Clinical Trial
  • Interferon Nonresponders
  • Interferon Therapy
  • Liver Cancer

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Lok, A. S., Everhart, J. E., Wright, E. C., Di Bisceglie, A. M., Kim, H., Sterling, R. K., Everson, G. T., Lindsay, K. L., Lee, W. M., Bonkovsky, H. L., Dienstag, J. L., Ghany, M. G., Morishima, C., & Morgan, T. R. (2011). Maintenance peginterferon therapy and other factors associated with hepatocellular carcinoma in patients with advanced hepatitis C. Gastroenterology, 140(3), 840-849.e1. https://doi.org/10.1053/j.gastro.2010.11.050