HLA class I allelic diversity and progression of fibrosis in patients with chronic hepatitis C.
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.
Patel
Keyur
K
Division of Gastroenterology, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27715, USA.
Norris
Suzanne
S
Lebeck
Lauralynn
L
Feng
Anne
A
Clare
Michael
M
Pianko
Stephen
S
Portmann
Bernard
B
Blatt
Lawrence M
LM
Koziol
James
J
Conrad
Andrew
A
McHutchison
John G
JG
D000328:Adult; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005805:Genes, MHC Class I; D014644:Genetic Variation; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies