Human leukocyte antigen class II and III alleles and severity of hepatitisC virus-related chronic liver disease

Hepatitis C outcome is likely related both to viral factors and host's immu ne responses. We correlated the severity of liver disease with human leukoc yte antigen (HLA) genes (C4A, C4B, TNFA, TNFB, DRB1, DRB3, DRB4, DRB5, DQA1 , DQB1, TAP1, and TAP2) in three groups of subjects: 99 patients with chron ic hepatitis, 41 asymptomatic carriers, and 179 uninfected controls. Patien ts with grade/stage 3 to 4 hepatitis significantly differentiated for their low frequency of alleles TNFB*1, DRB1*1104, and DRB3*03, which had a prote ctive role, and high frequency of allele DRB1*1001, which was associated wi th disease severity HLA-DRB*11 subtypes were differentially distributed: DR B1*1104 was most frequent in carriers, whereas DRB1*1101 was more frequent in patients. The TAP1C,2A haplotype was also underrepresented in patients w ith respect to controls. Finally, a decrease of heterozygous subjects was o bserved in patients with respect to carriers at the DQB1 locus. Multivariat e analysis by correspondence analysis and multiple logistic regression indi cated that age, sex, and hepatitis C virus (HCV) type were the strongest ri sk factors; however, some immunogenetic variables (TNFB*1, DRB1*1101, and D RB3*03) showed an independent contribution, especially in comparing patient s with extreme manifestations of disease. The involvement of different gene s in various HLA subregions suggests that anti-HCV responses are modulated by a complex gene interplay rather than by single alleles.