Viral hepatitis remains a significant global health challenge, with infections caused by hepatitis A (HAV), B (HBV), C (HCV), D (HDV), and E (HEV) viruses. Co-infections with two or more of these viruses are increasingly recognized as a critical clinical concern, often leading to more severe liver disease, accelerated progression to cirrhosis and hepatocellular carcinoma (HCC), and greater challenges in management compared to mono-infections. This article reviews the clinical course and specific features of combined viral hepatitis infections. We delve into the epidemiology, virological and immunological interactions, clinical manifestations, diagnostic approaches, and treatment strategies for the most common and clinically significant co-infection patterns, including HBV/HCV, HBV/HDV, and HAV/HEV. The impact of underlying immunosuppression, particularly from concurrent HIV infection, on the natural history of these co-infections is also discussed. Through a comprehensive review of existing literature and data, this paper highlights the heightened morbidity and mortality associated with viral hepatitis co-infections and underscores the necessity for integrated screening, diagnosis, and management approaches to improve patient outcomes.

Viral Hepatitis, Co-infection, Hepatitis B Virus, Hepatitis C Virus, Hepatitis D Virus, Liver Cirrhosis, Hepatocellular Carcinoma

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