1. Amino acid substitutions in hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by antiviral therapy.
- Author
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Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, and Kumada H
- 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
- 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., (Copyright © 2011 Wiley-Liss, Inc.)
- Published
- 2011
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