The Global Epidemiology of Hepatitis E Virus Infection

A Systematic Review and Meta-analysis

Pengfei Li; Jiaye Liu; Yang Li; Junhong Su; Zhongren Ma; Wichor M. Bramer; Wanlu Cao; Robert A. de Man; Maikel P. Peppelenbosch; Qiuwei Pan


Liver International. 2020;40(7):1516-1528. 

In This Article

Abstract and Introduction


Background and aims: Hepatitis E virus (HEV), as an emerging zoonotic pathogen, is a leading cause of acute viral hepatitis worldwide, with a high risk of developing chronic infection in immunocompromised patients. However, the global epidemiology of HEV infection has not been comprehensively assessed. This study aims to map the global prevalence and identify the risk factors of HEV infection by performing a systematic review and meta-analysis.

Methods: A systematic searching of articles published in Medline, Embase, Web of science, Cochrane and Google scholar databases till July 2019 was conducted to identify studies with HEV prevalence data. Pooled prevalence among different countries and continents was estimated. HEV IgG seroprevalence of subgroups was compared and risk factors for HEV infection were evaluated using odd ratios (OR).

Results: We identified 419 related studies which comprised of 1 519 872 individuals. A total of 1 099 717 participants pooled from 287 studies of general population estimated a global anti-HEV IgG seroprevalence of 12.47% (95% CI 10.42–14.67; I 2 = 100%). Notably, the use of ELISA kits from different manufacturers has a substantial impact on the global estimation of anti-HEV IgG seroprevalence. The pooled estimate of anti-HEV IgM seroprevalence based on 98 studies is 1.47% (95% CI 1.14–1.85; I 2 = 99%). The overall estimate of HEV viral RNA-positive rate in general population is 0.20% (95% CI 0.15–0.25; I 2 = 98%). Consumption of raw meat (P = .0001), exposure to soil (P < .0001), blood transfusion (P = .0138), travelling to endemic areas (P = .0244), contacting with dogs (P = .0416), living in rural areas (P = .0349) and receiving education less than elementary school (P < .0001) were identified as risk factors for anti-HEV IgG positivity.

Conclusions: Globally, approximately 939 million corresponding to 1 in 8 individuals have ever experienced HEV infection. 15–110 million individuals have recent or ongoing HEV infection. Our study highlights the substantial burden of HEV infection and calls for increasing routine screening and preventive measures.


Hepatitis E virus (HEV) as a positive-sense single-stranded RNA virus is a leading cause of acute viral hepatitis worldwide. The infection is usually asymptomatic or self-limiting in the general population. However, acute infection in pregnant women may cause severe clinical outcomes, including fulminant hepatic failure with high mortality rate reaching up to 20%-30%.[1] These patients are mostly from resource-limited regions. In European countries, HEV infection has been frequently reported to bear high risk of developing into chronic hepatitis in immunocompromised individuals, in particular organ transplant patients.[2,3] Thus, HEV is truly imposing a global health burden in both developing and developed countries.

Currently, eight distinct genotypes (GTs) of HEV have been classified.[4] GT 1–4 are known to be the main threat to humans. GT 1 and GT 2 are restricted to human and mainly transmit through contaminated water causing acute hepatitis. GT 3 and GT 4 are zoonotic and have been identified in a wide spectrum of hosts, including human, swine, wild boar, goat, cattle, deer, camel and yak.[5] Both GT 3 and GT 4 can cause chronic infection in organ transplant patients,[2,6] and consumption of raw or undercooked animal meat has been recognized as the main routes of causing sporadic cases in developed countries.[7] In fact, the host range of HEV is ever expanding and the implications of the rare GTs and the newly discovered strains in human health remain largely uncertain.[7] This further complicates the transmission and the risk of HEV infection. In addition to the classical waterborne and foodborne transmission routes, blood transfusion-mediated transmission has been reported in organ transplant patients.[8] Person-to-person transmission has also been proposed.[9] Intriguingly, recent evidence has indicated that pet animals including dogs, cats, rabbits and horses might be accidental hosts for HEV and constitute a potential source for transmitting to human.[10,11] Thus, there is an urgent need to comprehensively understand the risks for HEV infection, in order to device preventive measures.

Globally, it has been roughly estimated that one-third of the population are living in HEV endemic areas.[12] More recently, substantial efforts have been dedicated to systematically evaluate HEV prevalence in different continents (eg the Americas and Europe),[13,14] different countries (eg industrialized countries, China, Iran, Brazil and Somalia)[15–17] and special populations or settings (eg blood donors, swine workers and outbreak setting).[18–20] Most of these studies are based on seropositivity of anti-HEV IgG antibody. Anti-HEV IgG antibody developed post-infection usually persists for many years, and is thus regarded as a marker for past infection.[21,22] In contrast, anti-HEV IgM antibody is short-lived up to a few months, thus considered as evidence of recent or current infection. Detection of HEV RNA is a bona fide marker for active ongoing infection. In this study, we aimed to systematically estimate the global burden of HEV infection. More specifically, we have mapped the global prevalence of past, recent and ongoing HEV infection and evaluated the key risk factors of infection.