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Human leukocyte antigen class II and III alleles and severity of hepatitis C virus–related chronic liver disease
Author(s) -
Asti Margherita,
Martinetti Miryam,
Zavaglia Claudo,
Cuccia Maria Clara,
Gusberti Laura,
Tinelli Carmine,
Cividini Agostino,
Bruno Savino,
Salvaneschi Laura,
Ideo Gaetano,
Mondelli Mario U.,
Silini Enrico M.
Publication year - 1999
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510290445
Subject(s) - immunology , liver disease , hepatitis c virus , allele , virology , human leukocyte antigen , chronic liver disease , antigen , virus , hepatitis , medicine , disease , biology , gene , genetics , cirrhosis
Hepatitis C outcome is likely related both to viral factors and host's immune responses. We correlated the severity of liver disease with human leukocyte antigen (HLA) genes (C4A, C4B, TNFA, TNFB, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, TAP1, and TAP2) in three groups of subjects: 99 patients with chronic hepatitis, 41 asymptomatic carriers, and 179 uninfected controls. Patients 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 protective role, and high frequency of allele DRB1*1001, which was associated with disease severity. HLA‐DRB*11 subtypes were differentially distributed: DRB1*1104 was most frequent in carriers, whereas DRB1*1101 was more frequent in patients. The TAP1C,2A haplotype was also underrepresented in patients with respect to controls. Finally, a decrease of heterozygous subjects was observed in patients with respect to carriers at the DQB1 locus. Multivariate analysis by correspondence analysis and multiple logistic regression indicated that age, sex, and hepatitis C virus (HCV) type were the strongest risk factors; however, some immunogenetic variables (TNFB*1, DRB1*1104, and DRB3*03) showed an independent contribution, especially in comparing patients with extreme manifestations of disease. The involvement of different genes in various HLA subregions suggests that anti‐HCV responses are modulated by a complex gene interplay rather than by single alleles