Development of hepatocellular carcinoma in patients with hepatitis C virus infection who achieved sustained virological response following interferon therapy: A large-scale, long-term cohort study

J Gastroenterol Hepatol. 2016 May;31(5):1009-15. doi: 10.1111/jgh.13236.

Abstract

Background: We assessed the risk factors for the development of hepatocellular carcinoma (HCC) following successful eradication of hepatitis C virus (HCV) with interferon (IFN) therapy in a long-term, large-scale cohort study.

Methods: We reviewed 1094 consecutive patients with HCV who achieved sustained virological response (SVR) following IFN therapy between January 1995 and September 2013.

Results: During the observation period (median 50 months: range 13-224), 36 (3%) of 1094 patients developed HCC after SVR. The median period from SVR to diagnosis of HCC was 37 months (range 17-141), and the cumulative rates of HCC at 5, 10, and 15 years were 4%, 6%, and 12%, respectively. Multivariate analysis identified old age (≥60 years, HR, 3.1: 95%CI, 1.3-6.6: P = 0.009), male sex (HR, 12.0: 95%CI, 2.8-50.0: P < 0.0001), advanced fibrosis stage (F3/4, HR, 3.2: 95%CI, 1.6-7.2: P < 0.0001), and alpha-fetoprotein ≥10 ng/mL at 1 year after SVR (HR, 7.8: 95%CI, 2.9-16.8: P < 0.0001) as significant and independent risk factors for post-SVR HCC.

Conclusions: Older age and male sex (host factors), advanced fibrosis stage (pre-IFN treatment factor), and higher alpha-fetoprotein values (post-treatment factor) were significantly associated with HCC development after HCV eradication.

Keywords: hepatitis C virus; hepatocellular carcinoma; interferon therapy; sustained viral responders; α-fetoprotein.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / therapeutic use*
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / virology*
  • Chi-Square Distribution
  • Child
  • Female
  • Hepatitis C / complications
  • Hepatitis C / diagnosis
  • Hepatitis C / drug therapy*
  • Humans
  • Interferons / therapeutic use*
  • Kaplan-Meier Estimate
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / virology
  • Liver Function Tests
  • Liver Neoplasms / blood
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / virology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Severity of Illness Index
  • Sex Factors
  • Sustained Virologic Response*
  • Time Factors
  • Treatment Outcome
  • Up-Regulation
  • Young Adult
  • alpha-Fetoproteins / analysis

Substances

  • AFP protein, human
  • Antiviral Agents
  • alpha-Fetoproteins
  • Interferons