TOWARD PRECISION HEPATOLOGY: GENOMIC AND IMMUNOLOGIC DETERMINANTS OF DISEASE PROGRESSION IN CHRONIC HBV AND HCV INFECTION

Abstract

Hepatitis B and C remain significant causes of cirrhosis and hepatocellular carcinoma, especially in the Middle East, where HBV genotype D and HCV genotype 4 are predominant. Despite the expansion of vaccination programs and new direct-acting antivirals, many patients still progress to advanced liver disease due to complex host–virus interactions involving genetic, epigenetic, and immune system balance. This study compiles recent research on viral genotypes, host immunogenetic polymorphisms, and multi-omics advances to capture long-term profiles of liver injury. Key viral factors include the pathogenic roles of DNA integration and immune-escape mutations in HBV, as well as NS5A resistance variants in HCV. Host factors involve HLA allele diversity, interferon-lambda and cytokine gene polymorphisms, and immune checkpoint regulation. Multi-omics technologies, analyzing genomics, transcriptomics, proteomics, metabolomics, and immunomics, are shaping the era of precision hepatology by enabling detailed molecular profiling of tissues and responses to fibrosis stages. To maximize the benefits of precision hepatology in the Middle Eastern population, integrating with national genomic databases and linking to multi-omics data is crucial for identifying population-specific biomarkers. Additionally, translating detection into treatment through local biorepositories and omics collaboration is essential to improve national models, support Saudi Vision 2030, and achieve global hepatitis elimination goals.