Influence of amino-acid polymorphism in the core protein on progression of liver disease in patients infected with hepatitis C virus genotype 1b.

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.