title: Influence of amino-acid polymorphism in the core protein on progression of liver disease in patients infected with hepatitis C virus genotype 1b.
abstract: The substitution of amino acid (aa) 70 of arginine for glutamine and/or that of aa91 of leucine for methionine in the core protein in patients infected with hepatitis C virus (HCV) genotype 1b is associated with a poor response to pegylated interferon and ribavirin. Factors influencing these substitutions were sought in 1,097 patients infected with HCV-1b who had not received antiviral treatment. HCV variants with Arg70 and Leu91 (wild-type) decreased, while those with Gln70 and/or Met91 (mutant types) increased with age (P < 0.001). Of the 1,097 patients, 464 (42.3%) were infected with the Gln70 variant and the remaining 633 patients with the Arg70 variant. The proportion of patients with the Gln70 variant increased with the severity of liver disease (P < 0.001), elevated gamma-glutamyl transpeptidase (gamma-GTP) levels (P < 0.001) and a decrease in platelet count (P = 0.008). In univariate analysis patients with hepatocellular carcinoma, elevated aspartate aminotransferase (AST > or = 58 IU/L) and gamma-GTP (> or =61 IU/L), and decreased albumin levels (<3.9 g/dl) were more frequent in the patients with the Gln70 variant than the Arg70 variant (P = 0.003, 0.005, <0.001, and 0.031, respectively). In multivariate analysis HCC (odds ratio 1.829 [95% confidence interval 1.147-2.917]) and gamma-GTP > or =61 IU/L (1.647 [1.268-2.139]) increased the risk for the Gln70 variant. In conclusion, the substitution of amino aa70 of Arg for Gln in patients infected with HCV-1b increases with age, and it is associated with severe liver disease accompanied by elevated AST and gamma-GTP levels, as well as the development of hepatocellular carcinoma.
authors: Research Institute for Hepatology, Toranomon Hospital, Tokyo, Japan. vj7m-kbys@asahi-net.or.jp
authors: Mariko
authors: M
authors: Kobayashi
authors: Norio
authors: N
authors: Akuta
authors: Fumitaka
authors: F
authors: Suzuki
authors: Tetsuya
authors: T
authors: Hosaka
authors: Hitomi
authors: H
authors: Sezaki
authors: Masahiro
authors: M
authors: Kobayashi
authors: Yoshiyuki
authors: Y
authors: Suzuki
authors: Yasuji
authors: Y
authors: Arase
authors: Kenji
authors: K
authors: Ikeda
authors: Sachiyo
authors: S
authors: Watahiki
authors: Rie
authors: R
authors: Mineta
authors: Satomi
authors: S
authors: Iwasaki
authors: Yuzo
authors: Y
authors: Miyakawa
authors: Hiromitsu
authors: H
authors: Kumada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D006528:Carcinoma, Hepatocellular / Q000503:physiopathology* / Q000821:virology; D018450:Disease Progression; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D006526:Hepatitis C / Q000503:physiopathology* / Q000821:virology; D018936:Hepatitis C Antigens / Q000235:genetics; D006801:Humans; D008103:Liver Cirrhosis / Q000503:physiopathology* / Q000821:virology; D008113:Liver Neoplasms / Q000503:physiopathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D014758:Viral Core Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D018936:Hepatitis C Antigens; D014758:Viral Core Proteins