Current global estimates, risk factors, and knowledge gaps for Hepatitis E virus (HEV): A scoping review

Hepatitis E virus (HEV) remains a leading cause of acute viral hepatitis globally, particularly in South Asia and Africa. However, epidemiological prioritization is hampered by fragmented data and discordant disease burden estimates. Following JBI and PRISMA-Sc guidelines, we conducted a scoping review of global HEV evidence. We used the PCC framework: (P) general and high-risk populations (pregnant women, immunocompromised, and displaced groups); (C) quantitative estimates of burden, risk factors, or virological gaps; and (C) global evidence across all WHO regions to include studies. We searched PubMed, Scopus, and Web of Science, supplemented by country-specific searches in Google Scholar and IHME. From 11,583 citations, 395 articles met the inclusion criteria. The temporal distribution shows a marked increase in research volume, with 65.3% of studies published after 2010; however, 54.9% relied on observational descriptive designs while experimental investigations remained infrequent (4.3%). We identified three estimates of the global burden of HEV: the IHME Global Burden of Disease (GBD) published in 2021 (19.4 million cases) and two widely cited systematic reviews published in 2012 (20.1 million infections) and 2020 (939 million infections). A significant virological "blind spot" was observed, as 47.8% of studies did not report genotype information, though Genotype 3 (21.8%) was the most frequently identified among specified reports. Key risk domains identified were environmental (sanitation/water contamination) and cultural/occupational practices. Pregnant women, immunocompromised patients, and patients with pre-existing liver conditions were high at-risk populations. Key knowledge gaps identified were limited confidence in burden of disease estimates: severe molecular blind spots and evidence deserts, limited public health resources for surveillance, diagnostics, and reporting of cases and deaths in highest risk settings; exclusion of outbreaks from estimates of the burden of disease and unreliable convenience sample derived estimates. Hepatitis E virus is often neglected by international communities, global actors and national governments. However, it is difficult for stakeholders to prioritize a pathogen with highly variable and unreliable global burden of disease estimates. Comprehensive country level data based on more access to routine testing could facilitate global initiatives to devise strategies for equitable vaccination and mitigate the morbidity and mortality associated with this vaccine-preventable disease.