HLA Class II Alleles Are Associated With Histological Inflammatory Features of Steatohepatitis (NASH): Presidential Poster

Abstract

Introduction: The genotype-phenotype interaction in chronic liver diseases is a subject of growing interest. Previous studies have linked liver fibrosis susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class II alleles and histological characteristics and severity in patients with NAFLD/ NASH. Methods: DNA from biopsy-proven NAFLD patients was genotyped using polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO) for HLA class II antigens (HLA-DR1, -DR3, -DP &-DQ). Liver biopsies were assessed for hepatic steatosis, inflammation, and fibrosis. Multivariate analysis was performed to draw correlations between HLA antigen frequencies and the different variables; p≤0.05 were considered to be significant. Results: The study cohort include 85 patients with biopsy-proven NAFLD [age=44.25±10.78 years; female=68 (80.0%); white=59 (69.41%); NASH=35 (41.18%); diabetes mellitus=44 (22.4%); hyperlipidemia= 48 (56.47%) 75(38.9%), hypertension=46 (54.12%)]; diabetes=30 (35.29%); portal Inflammation=46 (54.12%), lobular Inflammation: [Kupffer cell hypertrophy=3 (3.8%%), inflammatory cells=18 (21.18%), polymorhnuclear cells=9 (10.59%)], [pericellular fibrosis=33 (38.82%), portal fibrosis=53 (62.35%); bridging fibrosis and cirrhosis=13 (15.29%)] and controls (N=55) without liver disease. DPB1*03 was found to be associated with patients with advanced steatosis [N=7 (31.82%) vs. non-steatosis N=6 (9.52%), p=0.01]. Interestingly DQA*05 was found to be associated with apoptosis and necrosis [N=25 (35.71%) vs. 1 (6.67%, p=0.02]. DRB3*01 was only found in patients with apoptotic or necrotic markers [N=16 (22.86%) vs. 0 (0.00%), p=0.03]. DQA1*03 was associated with higher risk of inflammation [n= 7 (53.85%) vs. 17 (25.76%), p=0.04] than those without inflammation. Inversely, DPA1*01 [n= 3 (33.33%) vs. 64 (84.21%), p<0.001], DPB1*04 [n= 0 (0.00%) vs. 47 (61.84%), p<0.001], DQB1*03 [n=2 (22.22%) vs. 49 (64.47%), p=0.01], and DRB4*01 [n= 2 (22.22%) vs. 47 (61.84%), p=0.04] were associated with lower risk of any type of inflammation. In multivariate analysis, DQA1*03 was independently associated with inflammation [odds ratio (OR): 6.12 (95% CI 1.39-27.73; p=0.01), while DPA1*01 was independently associated with lower risk of any type of inflammation (OR 0.08; 95% CI 0.01-0.61; p =0.01]. Conclusion: HLA-class II genes play important role in determining the disease mechanisms. DQA1*03 alleles play important role in predisposing to sever histological features of NASH among patients with NALFD. These HLA class II alleles that are risk haplotypes may help identify NAFLD patients with increased risk for developing inflammation and sever liver disease.