title: Amino acid substitutions in hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by antiviral therapy.
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.
authors.affiliation: Department of Hepatology, Toranomon Hospital, Tokyo, Japan. akuta-gi@umin.ac.jp.
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Miharu
authors.initials: M
authors.lastname: Hirakawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sezaki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saitoh
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arase
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000209:etiology*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D015994:Incidence; D007372:Interferons / Q000627:therapeutic use; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects / Q000235:genetics; D012254:Ribavirin / Q000627:therapeutic use; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D012254:Ribavirin; D007372:Interferons