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.

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.

• Authors: Yuya Seko, Norio Akuta, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Yoshiyuki Suzuki, Tetsuya Hosaka, Masahiro Kobayashi, Mariko Kobayashi, Satoshi Saitoh, Yasuji Arase, Kenji Ikeda, Hiromitsu Kumada
• Journal: Intervirology (Intervirology) Vol. 56 Issue 1 Pg. 13-21 ( 2013) ISSN: 1423-0100 [Electronic] Switzerland
• PMID: 22907167 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 S. Karger AG, Basel.

Chemical References

• Antiviral Agents
• Cholesterol, HDL
• Viral Core Proteins
• nucleocapsid protein, Hepatitis C virus
• Ribavirin
• Interferons

Topics

• Amino Acid Substitution
• Antiviral Agents (therapeutic use)
• Carcinoma, Hepatocellular (blood, epidemiology, virology)
• Cholesterol, HDL (blood)
• Drug Resistance, Viral
• Drug Therapy, Combination
• Genotype
• Hepacivirus (drug effects, genetics)
• Hepatitis C (complications, drug therapy)
• Humans
• Interferons (administration & dosage, therapeutic use)
• Liver Neoplasms (blood, epidemiology, virology)
• Ribavirin (administration & dosage, therapeutic use)
• Risk Factors
• Viral Core Proteins (genetics)
• Viral Load