Hepatitis E virus (HEV) infection has emerged as a significant cause of acute viral hepatitis worldwide, with disproportionate impact in developing countries.

Traditionally overshadowed by hepatitis A, B, and C, HEV is now recognized as a critical public health concern, particularly due to its severe outcomes in vulnerable populations and evolving epidemiology.

Virology and Genotypes: Understanding HEV's Complexity

Hepatitis E virus is a small, non-enveloped, single-stranded RNA virus belonging to the Hepeviridae family. It comprises at least eight distinct genotypes, each with unique epidemiological and clinical features. Genotypes 1 and 2 are restricted to humans and predominantly cause large waterborne outbreaks in low-resource settings. Meanwhile, genotypes 3 and 4 are zoonotic, circulating in animal reservoirs such as swine and causing sporadic infections in industrialized countries through zoonotic transmission.

Recent genetic analyses have uncovered emerging variants, underscoring HEV's adaptive evolution and the challenges in vaccine development. Dr. Mary J. Stephenson, a virologist at the University of Liverpool, notes, "The diversity within HEV strains demands a nuanced approach to diagnosis and preventive strategies tailored to regional epidemiology."

Transmission Pathways: Beyond the Waterborne Paradigm

Historically, HEV outbreaks have been linked to contaminated drinking water, reflecting inadequate sanitation infrastructure in many developing regions. However, current evidence reveals a broader range of transmission modes including food-borne, zoonotic, and parenteral routes.

Food products such as undercooked, wild game, and shellfish have been implicated in HEV transmission, especially for genotypes 3 and 4. Additionally, vertical transmission from mother to fetus and nosocomial infections via contaminated blood products highlight the virus's versatility.

Recent studies emphasize the urgent need for improved blood screening protocols in endemic areas. Dr. Rajesh Mehta, infectious disease specialist at AIIMS Delhi, warns, "Silent HEV infections in blood donors pose a hidden risk that could exacerbate outbreaks if not addressed promptly."

Clinical Spectrum: From Mild Infection to Severe Hepatic Failure

Acute hepatitis E typically manifests as a self-limited illness with jaundice, malaise, nausea, and elevated liver enzymes. However, severity varies widely. Pregnant women, particularly in the third trimester, face a dramatically higher risk of fulminant hepatic failure, with case fatality rates approaching 25%.

Chronic HEV infection, once considered rare, is increasingly reported among immunocompromised individuals such as transplant recipients and HIV-positive patients. Persistent viremia in these populations can lead to progressive liver fibrosis and cirrhosis.

Diagnostic Challenges and Advances

Definitive diagnosis relies on detecting HEV RNA by reverse transcription PCR in blood or stool samples, complemented by serological assays for anti-HEV IgM and IgG antibodies. Nevertheless, serological tests can exhibit cross-reactivity and variable sensitivity depending on genotype and assay design.

Recent advancements include highly sensitive molecular assays and next-generation sequencing techniques facilitating early detection and outbreak investigation. Integration of point-of-care molecular diagnostics could revolutionize HEV management in resource-limited settings.

Therapeutic Approaches and Vaccine Development

Currently, no specific antiviral therapy is approved for hepatitis E. Supportive care remains the cornerstone of treatment. Ribavirin has demonstrated efficacy in chronic HEV cases, particularly among immunosuppressed patients, though its use requires careful monitoring due to potential hematological toxicity.

Encouragingly, a recombinant HEV vaccine (HEV 239 or Hecolin) licensed in China has shown high efficacy in preventing infection by genotype 1. Yet, global availability is limited, and questions remain regarding cross-genotype protection and use in high-risk groups such as pregnant women. Dr. Elena García, vaccine researcher at WHO, emphasizes, "Scaling up vaccination efforts could transform HEV control, but robust data on long-term efficacy and safety in diverse populations are needed."

Public Health Strategies: Addressing a Multifaceted Challenge

Efforts to curb HEV transmission in developing regions must prioritize water sanitation improvements, food safety education, and strengthening healthcare infrastructure. Blood donation screening and enhanced surveillance systems are vital to detect and contain outbreaks rapidly.

A multidisciplinary approach involving environmental scientists, clinicians, and public health officials—aligned with the One Health concept—offers the most promising framework to mitigate this rising threat.

Hepatitis E is no longer a neglected tropical disease but a pressing global medical challenge with complex virology, diverse transmission routes, and significant morbidity among vulnerable groups. Advances in diagnostics, therapeutics, and vaccines hold promise, yet comprehensive, region-specific strategies are crucial to reduce the growing burden in developing regions.