Association of HLA DRB1 Allele Profile with Pediatric Autoimmune Liver Disease in India

Abstract

The aim of this study is to study the association of human leukocyte antigen (HLA) DRB1 alleles with treatment response in Indian children with autoimmune liver disease (AILD). HLA DRB1 alleles of 71 Indian children with pediatric AILD (pAILD) were analyzed along with 25 genetically confirmed patients with Wilson disease as controls. After 1 year of therapy, all those who failed to normalize aspartate & alanine transferase (AST/ ALT) (below 1.5 times of upper limit of normal) and/or failed to normalize IgG levels, or who had >2 relapses (AST/ALT levels >1.5 times of upper limit of normal) while on treatment, were labeled as difficult to treat (DTT). HLA DRB1∗3 was found to be significantly associated with AIH type 1 (46.2% vs. 4% in controls; P corrected=0.011). Majority of the patients [55 (77.5%)] had chronic liver disease at presentation, with 42 (59.2%) having portal hypertension and 17 (23.9%) having ascites. Out of the 71 with pAILD, 19 (26.8%) were DTT. HLA DRB1∗14 was found to be independently associated with DTT cases (36.8% vs. 9.6%, OR 5.87, 95% CI 1.07-32.09, P= 0.041). Other factors independently associated with DTT were presence of autoimmune sclerosing cholangitis (OR 8.57, P=0.008) and high-risk varices (OR 7.55, P=0.016), improving the correctness of classification of the model from 73.2% to 84.5%. HLA DRB1∗14 is independently associated with treatment response in pAILD and HLA DRB1∗3 is associated with AIH type 1. HLA DRB1 alleles may thus provide supportive information for diagnosis and prognosis of AILD.