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Amino Acid Substitutions in the Hepatitis C Virus Core Region and Lipid Metabolism Are Associated with Hepatocarcinogenesis in Nonresponders to Interferon plus Ribavirin Combination Therapy

Authors
  • Seko, Yuya
  • Akuta, Norio
  • Suzuki, Fumitaka
  • Kawamura, Yusuke
  • Sezaki, Hitomi
  • Suzuki, Yoshiyuki
  • Hosaka, Tetsuya
  • Kobayashi, Masahiro
  • Kobayashi, Mariko
  • Saitoh, Satoshi
  • Arase, Yasuji
  • Ikeda, Kenji
  • Kumada, Hiromitsu
Type
Published Article
Journal
Intervirology
Publisher
S. Karger AG
Publication Date
Aug 16, 2012
Volume
56
Issue
1
Pages
13–21
Identifiers
DOI: 10.1159/000339993
PMID: 22907167
Source
Karger
Keywords
License
Green
External links

Abstract

Background: Substitution of amino acid 70 and/or 91 in the core region of hepatitis C virus (HCV) genotype 1b (HCV-1b) is an important predictor of hepatocellular carcinoma (HCC), but its impact on HCC in nonresponders to interferon (IFN) and ribavirin (RIB) combination therapy is not clear. Methods: A total of 292 patients with HCV-1b-related chronic liver disease who did not achieve a sustained virological response to 24–48 weeks of IFN+RIB combination therapy were included in a follow-up study to investigate the risk factors for HCC. Results: Sixteen patients developed HCC during the follow-up. The cumulative HCC rates were 5.0, 13.1 and 16.9% at the end of 3, 5 and 7 years, respectively. Multivariate analysis identified substitution of core amino acid 70 (Gln70/His70; hazard ratio 4.64, p = 0.018) and low serum levels of high-density lipoprotein cholesterol (<50 mg/dl; hazard ratio 9.35, p = 0.041) as determinants of HCC. Gender, stage of fibrosis and interleukin-28B showed no such relationship. Conclusions: Amino acid substitution in the core region of HCV-1b and low serum levels of high-density lipoprotein cholesterol are significant and independent predictors of HCC in nonresponders to IFN+RIB combination therapy. These results emphasize the importance of viral and lipid metabolic factors in the development of HCC after combination therapy.

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