Genetic susceptibility and HLA association in autoimmune hepatitis among Yemeni patients

Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver disease characterized by the progressive destruction of hepatocytes, often leading to cirrhosis and liver failure. Genetic predisposition, particularly the involvement of human leukocyte antigen (HLA) alleles, is well-documented in the pathogenesis of AIH. However, the specific HLA associations in the Yemeni population remain unexplored, despite increasing clinical evidence of AIH in this region.

This study aims to elucidate the distribution of HLA class alleles in Yemeni patients (aged ≥ 18 years) with AIH and assess their association with disease susceptibility, contributing to the growing body of immunogenetic research in Middle Eastern populations.

This case-control study included 93 AIH patients and 280 healthy controls (total N = 373), all of Yemeni origin. We conducted high-resolution HLA typing and compared the frequencies of HLA alleles with global data. Allelic distributions were analyzed for associations with AIH susceptibility, and findings were interpreted in the context of previously identified genetic markers of autoimmune liver disease.

The most frequent allele in Yemeni AIH patients was HLA-DRB1*03:01 (42.5% vs. 15.5% in controls, OR = 4.0, 95% CI = 2.8-5.8, p = 0.01), followed by HLA-DRB1*04:01 (21.5% vs. 16.9%, OR = 1.3, 95% CI = 1.1-2.0, p = 0.04) and HLA-A*02 (31.7% vs. 27.9%, OR = 1.2, 95% CI = 1.1-1.3, p = 0.001). Protective alleles such as HLA-DRB1*13:01 were significantly more frequent in controls (13.2% vs. 3.8%, OR = 0.3, 95% CI = 0.1-0.6, p = 0.001). Our results demonstrate a genetic predisposition to AIH in Yemen, primarily associated with the HLA-DRB1*03:01 and HLA-DRB1*04:01 alleles. The observed distribution aligns with international trends but also reveals distinct ethnic-specific patterns that warrant further investigation.

This study highlights the critical role of HLA-DRB1* alleles, particularly DRB1*03:01 and DRB1*04:01, in the genetic susceptibility to AIH in the Yemeni population. These findings not only enhance the understanding of genetic factors in AIH but also establish a foundation for future immunogenetic research in the Middle East. The identification of region-specific HLA associations could inform both diagnostic and therapeutic strategies for AIH in Yemen and similar populations. This study was restricted to adults (≥ 18 years); therefore, findings may not apply to pediatric AIH.