Distinct Clinical Patterns Associated with HLA-DRB1 Genotypes in Pediatric Autoimmune Liver Diseases

Autoimmune liver diseases (AILD), including autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC), are rare but important causes of chronic liver disease in children. Although HLA-DRB1 alleles have been associated with disease susceptibility, their role in modulating the clinical phenotype and long-term outcome of pediatric AILDs remains incompletely understood. We aimed to characterize the distribution of HLA-DRB1 alleles and genotype combinations and describe the accompanying clinical features in a pediatric AILD cohort. Thirty children diagnosed with AIH-1 (n = 14), AIH-2 (n = 6), or ASC (n = 10) underwent HLA-DRB1 genotyping. Clinical presentation, fibrosis stage, treatment response, and associated autoimmune diseases were retrospectively analyzed. The most frequent alleles copies were HLA-DRB1*03 (n = 15), predominantly identified in AIH, and HLA-DRB1*13 (n = 14), identified in both AIH and ASC. Genotype combinations involving these alleles were observed across a broad spectrum of clinical presentations, fibrosis stages, treatment responses, and extrahepatic autoimmune manifestations. In this small cohort, HLA-DRB1*14-containing genotypes were observed in several patients with severe disease features, including advanced fibrosis, cirrhosis, treatment-refractory disease, and ulcerative colitis. Patients carrying HLA-DRB1*11, HLA-DRB1*15, or HLA-DRB1*16 had favorable hepatic outcomes despite severe initial presentation or associated extrahepatic autoimmune manifestations; however, the number of carriers was small. Clinical features varied among patients carrying different genotype combinations; however, the independent contribution of the accompanying allele could not be assessed. Our findings illustrate marked clinical heterogeneity among children carrying different HLA-DRB1 alleles and genotype combinations. In this exploratory cohort, selected HLA-DRB1 combinations co-occurred with distinct clinical patterns. HLA profiling may have a role in future risk stratification and individualized follow-up of children with AILD, but these observations are hypothesis-generating, they do not support genotype-based clinical management and require validation in larger, multicenter cohorts.