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Amino acid substitutions in hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by antiviral therapy.
- Source :
-
Journal of medical virology [J Med Virol] 2011 Jun; Vol. 83 (6), pp. 1016-22. - Publication Year :
- 2011
-
Abstract
- Substitution of amino acid (aa) 70 and/or 91 in the core region of HCV genotype 1b (HCV-1b) is an important predictor of hepatocarcinogenesis, but its impact on the development of hepatocellular carcinoma (HCC) following eradication of HCV RNA by antiviral therapy is not clear. 1,273 patients with HCV-related chronic liver disease, with sustained virological response, defined as negative HCV RNA at 24 weeks after cessation of interferon monotherapy or interferon plus ribavirin combination therapy, were included in a follow-up study to evaluate the impact of aa substitution in the core region on hepatocarcinogenesis. Twenty six patients developed HCC during the follow-up. The cumulative rates of new HCC were 3.2%, 4.8%, and 8.6% at the end of 5, 10, and 15 years, respectively. The rates in patients infected with HCV-1b/Gln70(His70) [glutamine (histidine) at aa 70] were significantly higher than in patients infected with HCV-1b/Arg70 (arginine at aa 70) (P = 0.007; log-rank test) and HCV-2a/2b (P < 0.001; log-rank test). The rates in patients infected with HCV-1b/Arg70 were not significantly higher than in those infected with HCV-2a/2b (P = 0.617; log-rank test). Multivariate analysis identified HCV-1b/Gln70(His70) (HR 10.5, P < 0.001), advanced fibrosis (HR 9.03, P = 0.002), and old age (HR 3.09, P = 0.066) as determinants of hepatocarcinogenesis. In conclusion, aa substitution in the core region of HCV-1b at the start of antiviral therapy is an important predictor of HCC following eradication of HCV RNA. This study emphasizes the importance of detection of aa substitutions in the core region before antiviral therapy.<br /> (Copyright © 2011 Wiley-Liss, Inc.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Amino Acid Substitution genetics
Carcinoma, Hepatocellular diagnosis
Drug Therapy, Combination
Female
Follow-Up Studies
Genotype
Hepacivirus classification
Hepacivirus drug effects
Hepatitis C, Chronic complications
Hepatitis C, Chronic virology
Humans
Incidence
Interferons therapeutic use
Liver pathology
Liver Neoplasms diagnosis
Male
Middle Aged
RNA, Viral blood
RNA, Viral drug effects
RNA, Viral genetics
Ribavirin therapeutic use
Viral Core Proteins chemistry
Young Adult
Antiviral Agents therapeutic use
Carcinoma, Hepatocellular etiology
Hepacivirus genetics
Hepatitis C, Chronic drug therapy
Liver Neoplasms etiology
Viral Core Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1096-9071
- Volume :
- 83
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of medical virology
- Publication Type :
- Academic Journal
- Accession number :
- 21503914
- Full Text :
- https://doi.org/10.1002/jmv.22094