Viral Hepatitis: An Update on Biology, Pathogenesis and Diagnosis

Abstract

Viral hepatitis remains one of the leading causes of liver-related morbidity and mortality worldwide, despite major advances in vaccination, antiviral therapy, and public health interventions. Hepatitis viruses A, B, C, D, and E differ in their genomic structure, modes of transmission, mechanisms of infection, and clinical outcomes, ranging from self-limiting acute disease to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. This review summarizes the historical development of hepatitis research and provides a comprehensive overview of the virology, epidemiology, mechanisms of viral entry, replication, and pathogenesis of the major hepatitis viruses. It further discusses current diagnostic approaches, including serological, molecular, imaging, and histopathological techniques, that enable early detection and disease monitoring. Recent therapeutic advances, particularly nucleos(t)ide analogues for hepatitis B, direct-acting antivirals for hepatitis C, and targeted therapies for hepatitis D, have substantially improved patient outcomes, although achieving a complete cure for chronic hepatitis B remains challenging due to the persistence of covalently closed circular DNA (cccDNA). Preventive strategies, including vaccination, blood safety, sanitation, and harm-reduction programmes, remain fundamental to disease control. Emerging therapeutic approaches such as gene-silencing technologies, capsid assembly modulators, CRISPR/Cas9-based genome editing, immune checkpoint inhibitors, and artificial intelligence-assisted disease prediction offer promising opportunities for future management. Continued research, expanded access to diagnosis and treatment, and coordinated global public health efforts are essential to achieve the World Health Organization's goal of eliminating viral hepatitis as a major public health threat by 2030.