Molecular Insights into Hepatitis Virus-Induced Hepatocarcinogenesis

Cancer is a multifactorial disease influenced by genetic, epigenetic, and environmental determinants, including biological agents such as oncogenic viruses. Among these, hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV) play pivotal roles in the pathogenesis of hepatocellular carcinoma (HCC)—the predominant form of primary liver cancer and a major contributor to global cancer mortality. Chronic infection with these hepatotropic viruses drives hepatocarcinogenesis through both direct mechanisms, including viral genome integration and oncoprotein expression, and indirect pathways involving persistent inflammation, immune evasion, and oxidative stress.Despite substantial advances in HBV vaccination programs and the development of curative therapies for HCV, the global burden of hepatitis-related liver cancer remains high, driven by underdiagnosis, limited access to care, and the absence of a functional cure for HBV.This review critically examines the molecular and pathogenic mechanisms by which HBV, HCV, and HDV contribute to cancer initiation and progression, and summarizes current therapeutic and preventive strategies. It further highlights emerging research directions and translational challenges that must be addressed to improve prevention, early detection, and treatment of virus-induced hepatocellular carcinoma.