Occult hepatitis B infection in Saudi Arabia: Molecular mechanisms, diagnostic challenges, and implications for HBV elimination.

Although universal HBV vaccination has markedly reduced the prevalence of overt HBV infection in Saudi Arabia, Occult hepatitis B infection (OBI) remains an underrecognized clinical and public health concern, associated with HBV reactivation during immunosuppression and progression to hepatocellular carcinoma. This review summarizes current evidence on the epidemiology, molecular mechanisms, diagnostic challenges, and public health implications of OBI in Saudi Arabia and across the Middle East. Important mechanisms include persistence of covalently closed circular DNA, viral genetic mutations, immune-mediated suppression, and epigenetic regulation of viral transcription. Despite progress in molecular diagnostics, challenges exist for optimal detection and surveillance of low-level viremia, including assay sensitivity, standardization, infrastructure, and cost, with the limitations of conventional serological screening and the increasing importance of nucleic acid testing. Strengthening integrated screening strategies, molecular surveillance, risk-based nucleic acid testing, and clinician awareness will be essential to support HBV elimination efforts by 2030.