Number of mutations within CTL-defined epitopes of the hepatitis B Virus (HBV) core region is associated with HBV disease progression (pages 2082–2087)

摘要

The virologic determinants of progressive liverndisease associated with hepatitis B virus (HBV)nremain unclear. Previous investigations havenassociated HBV disease with specific mutationsnbut this association may be confounded bynHBV genotype, HLA haplotype of the infectednindividual or both. The association betweennnon-synonymous mutations located within putativencytotoxic T-lymphocyte directed epitopesn(CDE) of the HBV core region and disease statesnwas investigated. Subjects infected with HBVnwere enrolled from a clinical cohort in Seoul,nKorea, and HBV core gene sequences were analyzednfor mutational patterns inside and outsidenof CDE with respect to subject demographicsnand HBV-related disease states. No specificnmutation or pattern of mutations were associatednwith progressive disease states; however,nindividuals with cirrhosis and hepatocellularncarcinoma had greater numbers of nonsynonymousnmutations within CDE when comparednto those with chronic HBV infection whonwere HBeAg positive (P ?0.007 and 0.026,nrespectively). In conclusion, this study demonstratesnthat HBV disease progression is associatednwith viral escape mutations that are anmarker of CTL activity. These data suggest thatnthe number of non-synonymous mutations innthe HBV core region may predict HBV diseasenprogression better than any single mutationnor pattern of mutations. J. Med. Virol. 83:n2082–2087, 2011. u0001 2011 Wiley Periodicals, Inc.