Mapping HLA class I and II allele associations with hepatitis C related liver disease progression in an Egyptian cohort

Abstract

BACKGROUND AND AIM: Host genetic factors, particularly human leukocyte antigen (HLA) polymorphisms, play a crucial role in determining the immunological outcome of Hepatitis C virus (HCV) infection. These genetic variations may influence susceptibility, disease progression, and the development of severe liver complications such as liver cirrhosis and hepatocellular carcinoma (HCC). Given the predominance of HCV genotype 4 in Egypt, this study was designed to investigate the association between specific HLA Class I and Class II alleles and clinical outcomes in an Egyptian cohort of patients with chronic HCV infection. PATIENTS AND METHODS: sequence-specific oligonucleotide (SSO) probe assay. Clinical and demographic data were collected between 2014 and 2016, before the implementation of Egypt's nationwide HCV eradication program, launched in 2018. RESULTS: This study identified differential HLA allele frequencies across HCV-related liver disease outcomes in an Egyptian cohort. HLA-DQB1*03, HLA-B*27, HLA-C*05, and HLA-A*26 showed high frequencies in healthy controls, whereas HLA-DRB1*14, HLA-A*69, HLA-B*52, HLA-B*58, and HLA-DRB1*15 appeared enriched in disease groups. Only HLA-DQB1*03 remained significant after Bonferroni correction. However, given the small sample size and lack of comprehensive national HLA data for direct comparison, these observations should be interpreted with caution. Alleles, such as HLA-B*44 and HLA-C*05, appeared absent in the HCC subgroup, though the significance of this finding remains uncertain due to low background frequencies in the control group. CONCLUSION: These preliminary data suggest possible associations of certain HLA alleles and HCV-related liver disease progression in Egyptian patients, possibly serving as candidate biomarkers for risk stratification. Nonetheless, larger, population-based studies with confirmed HCV genotyping, comprehensive treatment data, and updated controls reflecting current Egyptian HLA allele frequencies are needed to substantiate these associations.