Genetic predisposition to autoimmune hepatitis (AIH) in adults is associated with possession of HLA class I (A*01, B*08) and class II alleles (DRB1*03, -04, -07 or -13), depending on geographic regions. Juvenile autoimmune liver disease (AILD) comprises AIH-1, AIH-2 and autoimmune sclerosing cholangitis (ASC), which are phenotypically different from their adult counterparts. We aimed to define the relationship between HLA profile and disease course, severity and outcome in juvenile AILD.  We studied 236 children of European ancestry [152 females (64%), median age 11.15 years, range 0.8-17], including 100 AIH-1, 59 AIH-2 and 77 ASC. The follow up period was from 1977 to June 2019 (median 14.5 years). Class I and II HLA genotyping was performed using PCR/sequence specific primers.  HLA B*08, -DRB1*03 and the A1-B8-DR3 haplotype impart predisposition to all three forms of AILD. Homozygosity for DRB1*03 represented the strongest risk factor (8.8). HLA DRB1*04, which independently confers susceptibility to AIH in adults, was infrequent in AIH-1 and ASC, suggesting protection, and DRB1*15 (DR15) was protective against all forms of AILD. Distinct HLA class II alleles predispose to the different subgroups of juvenile AILD: DRB1*03 to AIH-1, DRB1*13 to ASC and DRB1*07 to AIH-2. Possession of homozygous DRB1*03 or of DRB1*13 is associated with fibrosis at disease onset, and possession of these two genes in addition to DRB1*07 is associated with a more severe disease in all three subgroups.  Unique HLA profiles are seen in each subgroup of juvenile AILD. HLA genotype might be useful in predicting responsiveness to immunosuppressive treatment and course. This article is protected by copyright. All rights reserved.