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Substitutions in interferon sensitivity-determining region and hepatocarcinogenesis after hepatitis C virus

Satoshi Yasuda1, Masatoshi Ishigami1, Yoji Ishizu1

  • 1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Journal of Gastroenterology and Hepatology
|May 11, 2018
PubMed
Abstract

Insights

Amino-acid substitutions in the interferon sensitivity-determining region (ISDR) predict hepatocellular carcinoma (HCC) risk in hepatitis C virus (HCV) patients after treatment. This finding aids in predicting HCC development post-sustained virological response (SVR).

Area of Science:

  • Hepatology
  • Virology
  • Oncology

Background:

  • Interferon (IFN) therapy is used for Hepatitis C Virus (HCV) infection.
  • Amino-acid substitutions in the Interferon Sensitivity-Determining Region (ISDR) of the NS5A gene correlate with IFN treatment response.
  • Previous research suggests a link between ISDR and Hepatocellular Carcinoma (HCC) development in HCV patients, but this is unclear post-sustained virological response (SVR).

Purpose of the Study:

  • To investigate the association between ISDR amino-acid substitutions and HCC development in HCV patients who achieved SVR.
  • To determine if ISDR mutations can predict HCC risk after successful HCV treatment.

Main Methods:

  • Analysis of 1,588 HCV patients treated with IFN-based therapy.
  • Focus on 475 patients who achieved SVR and had pretreatment virological data.
  • Direct sequencing of the ISDR region for HCV genotypes 1a, 1b, 2a, 2b, and 3a.

Main Results:

  • Nineteen patients developed HCC after SVR, with cumulative incidences of 2.1% at 5 years and 15.9% at 10 years.
  • Multivariate analysis identified older age (≥60 years), higher gamma-glutamyl transpeptidase levels (≥50 IU/L), and ≥3 ISDR substitutions as independent predictors of HCC development.
  • The hazard ratio for ≥3 ISDR substitutions was 3.24 (P=0.016).

Conclusions:

  • Amino-acid substitutions in the ISDR are valuable predictors of HCC development in HCV patients achieving SVR.
  • ISDR analysis can inform risk stratification for HCC in patients post-IFN therapy.
  • These findings extend the utility of ISDR analysis beyond predicting IFN responsiveness.
Keywords:
hepatitis Chepatocellular carcinomainterferon and pegylated interferon

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