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. (C) 2005 Blackwell Publishing Asia Pty Ltd.