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Background & Aims Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. We used a genome-wide approach to identify genetic variants that predispose individuals to AIH. Methods We performed a genome-wide association study of 649 adults in The Netherlands with AIH type 1 and 13,436 controls. Initial associations were further analyzed in an independent replication panel comprising 451 patients with AIH type 1 in Germany and 4103 controls. We also performed an association analysis in the discovery cohort using imputed genotypes of the major histocompatibility complex region. Results We associated AIH with a variant in the major histocompatibility complex region at rs2187668 (P = 1.5 x 10-78). Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3 x 10-49) as a primary susceptibility genotype and HLA-DRB1*0401 (P = 2.8 x 10-18) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 x 10-8) and CARD10 (rs6000782, 22q13.1; P = 3.0 x 10-6). In addition, strong inflation of association signal was found with single-nucleotide polymorphisms associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with single-nucleotide polymorphisms associated with other genetic traits. Conclusions In a genome-wide association study, we associated AIH type 1 with variants in the major histocompatibility complex region, and identified variants of SH2B3and CARD10 as likely risk factors. These findings support a complex genetic basis for AIH pathogenesis and indicate that part of the genetic susceptibility overlaps with that for other immune-mediated liver diseases. [ABSTRACT FROM AUTHOR]

Background and Aims: In recent years chronic courses of hepatitis E virus (HEV) infection have been described in immunosuppressed individuals. This may implicate a potential role for HEV in the development of autoimmune diseases, including autoimmune hepatitis (AIH). Here we investigated the prevalence of HEV-antibodies in AIH patients in an endemic Central European country., Methods: HEV-specific immunoglobulin G (IgG) and HEV RNA were determined in 354 and 377 AIH patients, respectively. Clinical characteristics and disease outcome parameters were retrospectively collected., Results: No HEV viraemic patients were identified in this cohort. A total of 106 AIH patients (29.9%) tested positive for anti-HEV IgG, and this figure was slightly higher compared to the prevalence in a reference cohort including 5,329 healthy Dutch blood donors (26.7%; P>0.05)., Conclusion: This is the largest study on the association between HEV infection and AIH. Apparently silent HEV infection is present in a significant proportion of AIH patients, yet appears not to have significant clinical repercussions in this immune compromised group of patients. Nevertheless, since acute hepatitis E may present with histological and biochemical features of AIH, the possibility of a (concomitant) HEV infection should be considered in this category of patients.