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HLA class I allelic diversity and progression of fibrosis in patients with chronic hepatitis C
Author(s) -
Patel Keyur,
Norris Suzanne,
Lebeck Lauralynn,
Feng Anne,
Clare Michael,
Pianko Stephen,
Portmann Bernard,
Blatt Lawrence M.,
Koziol James,
Conrad Andrew,
McHutchison John G.
Publication year - 2006
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.21040
Subject(s) - human leukocyte antigen , allele , immunology , genotype , cirrhosis , loss of heterozygosity , zygosity , locus (genetics) , biology , fibrosis , hepatitis c , hepatitis c virus , medicine , gastroenterology , antigen , genetics , virus , gene
Patients infected with HIV‐1 who are heterozygous at HLA class I loci present greater variety of antigenic peptides to CD8 + cytotoxic T lymphocytes, slowing progression to AIDS. A similar broad immune response in chronic hepatitis C (CHC) infection could result in greater hepatic injury. Although specific HLA class II alleles may influence outcome in CHC patients, the role of HLA class I heterogeneity is generally less clearly defined. Our aims were to determine whether HLA class I allelic diversity is associated with disease severity and progression of fibrosis in CHC. The study population consisted of 670 adults with CHC, including 155 with advanced cirrhosis, and 237 non–HCV‐infected controls. Serological testing for HLA class I antigens was performed via microlymphocytotoxicity assay. Peptide expression was defined as heterozygous ( i.e. , a different allele at each locus) or homozygous. Fibrosis staging was determined using METAVIR classification. Heterozygosity at the B locus (fibrosis progression rate [FPR] 0.08 vs. 0.06 units/yr; P = .04) and homozygosity at the A locus (FPR 0.10 vs. 0.08 units/yr; P = .04) predicted a higher median FPR. Age at infection, genotype, and duration of infection were also predictors of FPR. A higher proportion of patients with stage F2‐F4 expressed HLA‐B18 compared with controls (OR 2.2, 95% CI 1.17‐4.23; P = .02). These differences were not observed in patients with advanced cirrhosis. HLA zygosity at 1, 2, or 3 alleles was not associated with fibrosis stage, liver inflammation, or treatment outcome. In conclusion , HLA class I allelic diversity has a minor influence on FPRs and disease severity in CHC. (Hepatology 2006,43:241–249.)