The classical human leukocyte antigen (HLA)-DRB1* 03: 01 and HLA-DRB1* 04: 01 alleles are established autoimmune hepatitis (AIH) risk alleles. To study the immune-modifying effect of these alleles, we imputed the genotypes from genome-wide association data in 649 Dutch AIH type-1 patients. We therefore compared the international AIH group (IAIHG) diagnostic scores as well as the underlying clinical characteristics between patients positive and negative for these HLA alleles. Seventy-five percent of the AIH patients were HLA-DRB1* 03: 01/HLA-DRB1* 04: 01 positive. HLA-DRB1* 03: 01/HLA-DRB1* 04: 01-positive patients had a higher median IAIHG score than HLA-DRB1* 03: 01/HLA-DRB1* 04: 01-negative patients (P< 0.001). We did not observe associations between HLA alleles and alanine transaminase levels (HLA-DRB1* 03: 01: P= 0.2; HLA-DRB1* 04: 01; P= 0.5); however, HLA-DRB1* 03: 01 was independently associated with higher immunoglobulin G levels (P= 0.04). The HLA-DRB1* 04: 01 allele was independently associated with presentation at older age (P= 0.03) and a female predominance (P= 0.04). HLA-DRB1* 03: 01-positive patients received immunosuppressive medication and liver transplantation. In conclusion, the HLA-DRB1* 03: 01 and HLA-DRB1* 04: 01 alleles are both independently associated with the aggregate diagnostic IAIHG score in type-1 AIH patients, but are not essential for AIH development. HLA-DRB1* 03: 01 is the strongest genetic modifier of disease severity in AIH.