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HLA class I allelic diversity and progression of fibrosis in patients with chronic hepatitis C

Academic Article
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Overview

authors

  • Patel, K.
  • Norris, S.
  • Lebeck, L.
  • Feng, A.
  • Clare, M.
  • Pianko, S.
  • Portmann, B.
  • Blatt, L. M.
  • Koziol, James
  • Conrad, A.
  • McHutchison, J. G.

publication date

  • 2006

journal

  • Hepatology  Journal

abstract

  • 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.

subject areas

  • Adult
  • Disease Progression
  • Female
  • Gene Frequency
  • Genes, MHC Class I
  • Genetic Variation
  • Hepatitis C, Chronic
  • Heterozygote
  • Humans
  • Liver
  • Liver Cirrhosis
  • Male
  • Middle Aged
  • Retrospective Studies
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Identity

International Standard Serial Number (ISSN)

  • 0270-9139

Digital Object Identifier (DOI)

  • 10.1002/hep.21040

PubMed ID

  • 16440356
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Additional Document Info

start page

  • 241

end page

  • 249

volume

  • 43

issue

  • 2

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