Clinical significance of HLA DRB1*03?DRB1*04 in type 1 autoimmune hepatitis

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Abstract
Background: HLA DRB1*03–DRB1*04 combines both susceptibility factors for type‐1 autoimmune hepatitis. Aims: Determine whether this phenotype is a risk factor for autoimmune hepatitis in white North American patients, assess its associations with clinical features and treatment outcome, and determine whether alleles within this phenotype affect prognosis. Methods: One hundred and ninety‐eight patients with type 1 autoimmune hepatitis and 102 normal adults were evaluated. HLA typing was performed by DNA‐based techniques. Results: Twenty‐eight patients had HLA DRB1*03–DRB1*04, and the frequency was higher than in normal subjects (14% vs 4%, OR 4.0%, 95% CI 1.4–11.8, P=0.01). Patients with DRB1*03–DRB1*04 relapsed less frequently than patients with DRB1*03 (1.3±0.3 vs 2.1±0.2, P=0.04), but they otherwise had outcomes similar to patients with other phenotypes. Patients with DRB1*03‐DRB1*04 who had 3–4 alleles encoding lysine at position DRβ71 within the class II molecule of the major histocompatibility complex developed cirrhosis more commonly (75% vs 9%, P=0.05) and had a higher frequency of hepatic‐related death or liver transplantation (40% vs 0%, P=0.04) than patients with fewer alleles. Conclusions: HLA DRB1*03–DRB1*04 is a risk factor for type‐1 autoimmune hepatitis, and its impact on outcome relates to the diversity of DRB1*04 alleles that encode a critical motif.