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Association between HLA class II genotype and spontaneous clearance of hepatitis C viraemia. 1998

M E Cramp, and P Carucci, and J Underhill, and N V Naoumov, and R Williams, and P T Donaldson
Institute of Liver Studies, King's College Hospital, London, UK.

OBJECTIVE Hepatitis C virus (HCV) infection becomes chronic in most cases, with only 10-20% of those infected not developing persistent viraemia. The immune response to HCV may be an important determinant of disease resolution and can be influenced by a number of host factors. The aim of this study was to assess the role of host HLA class II type in influencing viral clearance or susceptibility to chronic HCV infection. METHODS We have compared the distribution of HLA DRB1, DQA1 and DQB1 alleles in 49 patients with spontaneous clearance of HCV infection (HCV antibody positive but persistently HCV RNA negative), with 55 chronically infected patients and 134 racially matched controls. RESULTS Three alleles were found significantly more frequently in patients with spontaneous viral clearance compared to those with chronic infection-DRB1*04 (pc=0.0022, odds ratio OR=4.52), DQA1*03 (pc=0.0012, OR=4.69) and DQB1*0301 (pc=0.0078, OR=5.09). DQB1*0302 was found at reduced frequency in all HCV-antibody-positive patients compared to controls (pc=0.0063). CONCLUSIONS DRB1*04, DQA1*03 and DQB1*0301 are associated with spontaneous clearance of HCV viraemia, with the primary association likely to be with DQB1*0301 and the associations with DRB1*04 and DQA1*03 being due to linkage. In addition, DQB1*0302 is associated with protection from HCV infection. These findings suggest that host HLA class II genotype is an important factor in determining the outcome of infection with hepatitis C virus.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008103 Liver Cirrhosis Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. Cirrhosis, Liver,Fibrosis, Liver,Hepatic Cirrhosis,Liver Fibrosis,Cirrhosis, Hepatic
D008297 Male Males
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D004198 Disease Susceptibility A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. Diathesis,Susceptibility, Disease,Diatheses,Disease Susceptibilities,Susceptibilities, Disease
D005260 Female Females
D005802 Genes, MHC Class II Genetic loci in the vertebrate major histocompatibility complex that encode polymorphic products which control the immune response to specific antigens. The genes are found in the HLA-D region in humans and include H-2M, I-A, and I-E loci in mice. Class II Genes,Genes, Class II,Genes, HLA Class II,MHC Class II Genes,Class II Gene,Gene, Class II
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006526 Hepatitis C INFLAMMATION of the LIVER in humans caused by HEPATITIS C VIRUS, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown. Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted,Parenterally-Transmitted Non-A, Non-B Hepatitis,PT-NANBH,Parenterally Transmitted Non A, Non B Hepatitis

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