Association of fulminant non-A non-B hepatitis with homozygosity for HLA A1-B8-DR3.
BACKGROUND
For the majority of cases of acute liver failure in western Europe and North America an etiology cannot be defined. The condition is most often called fulminant non-A, non-B (NANB) hepatitis. Features such as female preponderance and presence of serum autoantibodies suggest a possible autoimmune basis. The aim of the present paper was to examine a possible human leukocyte antigen (HLA) association with fulminant NANB hepatitis.


METHODS
HLA A, B, and DR data of 55 adult Caucasian fulminant NANB patients were compared with those of 1449 local Caucasian controls.


RESULTS
In Caucasian patients, homozygosity (but not heterozygosity) for the alleles A1, B8, and DR3 were associated with fulminant NANB hepatitis (Pcorrected = 0.02, <0.00001 and 0.002, respectively). Greatest relative risk (RR) was associated with homozygosity for the A1-B8-DR3 haplotype (P < 0.00001; RR: 12.8; 95% confidence interval [CI]: 5.7-22.3). HLA DR8 was also associated with development of the syndrome (RR: 4.2; 95%CI: 1.6-9.2).


CONCLUSIONS
Homozygosity for the HLA haplotype A1-B8-DR3 confers susceptibility to the development of fulminant NANB hepatitis. This observation may imply a role for the immune response genes (which are flanked by HLA B and DR) in the pathogenesis of this syndrome.
Gow
Paul
P
Gastroenterology Unit and Liver Transplant Unit, Austin Hospital, Heidelberg, Victoria, Australia. Paul.Gow@austin.org.au
Hathaway
Mark
M
Gunson
Bridget
B
Heward
Joanne
J
Mutimer
David
D
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006526:Hepatitis C / Q000235:genetics* / Q000276:immunology*; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D016031:Liver Transplantation; D008297:Male; D016133:Polymerase Chain Reaction; D044465:White People
D006680:HLA Antigens