Virological and immunological determinants of hepatitis E virus infection outcomes

Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis worldwide, especially in regions with limited sanitation infrastructure. Unlike hepatitis B virus (HBV) and hepatitis C virus (HCV) - which frequently progress to chronic infections associated with cirrhosis and hepatocellular carcinoma - HEV typically leads to acute and self-resolving infection in immunocompetent individuals. This review explores the mechanistic underpinnings that distinguish HEV's clinical trajectory from HBV and HCV, focusing on viral genome organization, replication strategies, immune evasion tactics, and host immune responses. Understanding these factors provides critical insights into the determinants of viral clearance versus persistence and may guide future vaccine and antiviral development.