Abstract
BACKGROUND: Hepatitis E virus (HEV) is a major cause of viral hepatitis in low- and middle-income countries, particularly in South Asia, where poor sanitation facilitates its fecal-oral transmission. Nepal, Bangladesh, and Pakistan experience a significant HEV burden, with severe outcomes in high-risk groups like pregnant women and hepatic patients, who face elevated mortality rates. This systematic review and meta-analysis aimed to estimate HEV seroprevalence in these countries, focusing on the general population, pregnant women, and hepatic patients, to inform public health strategies. METHODS: We searched PubMed, Embase, Cochrane Library, and ProMED-mail for studies published between 2000 and 2017, following PRISMA guidelines and a registered protocol [PROSPERO: CRD42018099558]. Studies reporting HEV seroprevalence in Nepal, Bangladesh, or Pakistan using serological or molecular methods were included. The original search period was retained as data extraction was completed in 2018, and including newer studies was not feasible. A random-effects meta-analysis was conducted using the 'metaprop' function in R, with heterogeneity assessed via I² and τ² statistics. Publication bias was evaluated using Egger's test and funnel plots. RESULTS: The meta-analysis included 64 studies, totaling 25,301 participants. Pooled HEV seroprevalence was 23.8% (95% CI: 13.7%-35.5%) in the general population (n = 9,935), 41.2% (95% CI: 27.6%-55.6%) in pregnant women (n = 4,345), and 41.8% (95% CI: 30.7%-53.4%) in hepatic patients (n = 11,021). High heterogeneity was observed (I²=98.3-99.4%), with significant country-level variation in hepatic patients (p = 0.0002). Subgroup analyses revealed country-specific variations, particularly for hepatic patients where Bangladesh and Nepal showed higher prevalence than Pakistan. Publication bias was evident in pregnant women (p = 0.0002) and hepatic patients (p = 0.0066), but not in the general population (p = 0.6235). CONCLUSIONS: These findings highlight the substantial burden of HEV in South Asia, with notable differences across population groups and countries. The high seroprevalence in hepatic patients and pregnant women underscores the need for targeted surveillance and intervention strategies like improved sanitation and vaccination. High heterogeneity and publication bias suggest cautious interpretation, and future research should focus on standardizing diagnostics and conducting longitudinal studies to assess temporal trends in HEV prevalence.