High-Resolution Genotyping of HLA Alleles and Association with Genetic Background of Virological Response in Chronic Hepatitis B.

Abstract

Background: Hepatitis B virus (HBV) infection is a major global health problem and can cause chronic infections and promote the development of cirrhosis and liver cancer. In the current investigation, we focused on evaluating the association between human leukocyte antigen (HLA) class I and II genotyping, HBV viral load, and the presence of steatosis in CHB (chronic hepatitis B) patients.

Methods: In this study, we evaluated 204 patients with CHB who did not receive antiviral therapy before inclusion in the study and during the follow-up period. All patients were divided into 2 categories based on their HBV DNA levels. The presence of hepatic steatosis was determined by an ultrasound examination and SteatoTest. HLA genotyping for 11 genes, including HLA class I and class II, was conducted using next-generation sequencing.

Results: Four HLA class II alleles, HLA-DQA1*01:02:02 (p = 0.019), HLA-DQB1*05:02:01 (p = 0.014), HLA-DRB1*16:01:01 (p = 0.032), and HLA-DRB5*02:02:01 (p = 0.052), were found to be positively associated with high levels of HBV-DNA. Furthermore, when studying the association of HLA class I and class II alleles with hepatic steatosis, our data showed that HLA-B*08:01:01 (p = 0.011), HLA-C*07:01:01 (p = 0.011), and HLA-DRB3*01:01:02 (p = 0.027) were positively correlated with the presence of hepatic steatosis.

Conclusions: Integrating next-generation sequencing data of HLA genes in genomic and epigenomic data can offer a comprehensive understanding of the molecular mechanisms underlying HBV infection. This integrated approach will help identify new biomarkers, deeply understand the complex interactions between genetic and epigenetic factors, and facilitate the development of personalized prevention and treatment strategies.