Clinical significance of HLA DRB103-DRB104 in type 1 autoimmune hepatitis

HLA DRB1*03-DRB1*04 combines both susceptibility factors for type-1 autoimmune hepatitis.

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.

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.

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 DRbeta71 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.

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.