Enterically Transmitted Viral Hepatitis: A Comprehensive Review of Hepatitis A and Hepatitis E — Epidemiology, Pathogenesis, Clinical Manifestations, Diagnostics, Treatment and Prevention

Enterically transmitted hepatitis, caused by hepatitis A virus (HAV) and hepatitis E virus (HEV), constitutes a major global public health burden driven by inadequate water and sanitation infrastructure, particularly in low- and middle-income countries. Despite sharing fecal-oral transmission routes, these two infections differ substantially in virology, epidemiology, clinical course, and outcome. HAV, a Picornaviridae member, invariably causes self-limiting acute hepatitis, with effective inactivated vaccines providing lifelong protection. HEV, classified within the Hepeviridae family, presents a more heterogeneous disease profile: epidemic strains (genotypes 1 and 2) cause large waterborne outbreaks in endemic regions and impose disproportionate mortality — up to 30% — in pregnant women, while zoonotic genotypes (3 and 4) circulate endemically in high-income countries and cause chronic hepatitis in immunocompromised patients, a complication absent in HAV infection. This review critically examines the virological characteristics, global and regional epidemiological trends, immunopathogenic mechanisms, clinical manifestations including high-risk populations, diagnostic advances, and current management strategies for both infections. Special attention is given to recent developments from 2019 to 2025, including updated WHO guidance, molecular epidemiology data, the expanding clinical phenotype of chronic HEV, and the unresolved issue of global HEV vaccine access. Significant gaps persist in HEV diagnostic standardization, equitable vaccine deployment, and antiviral development, which constitute priority areas for future research and policy.

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