Hepatitis E in Pregnant Women and the Potential Use of HEV Vaccine to Prevent Maternal Infection and Mortality

Abstract

Purpose of Review Hepatitis E (HEV) is a continuing public health problem in developing countries, causing high mortality in pregnant women. This article reviews the latest knowledge on HEV in pregnancy, the vaccine candidates that have reached clinical trials, and their potential use during pregnancy. Recent Findings New evidence suggests that a genotype-specific tropism to uteroplacental cells contributes to the multifactorial pathology leading to the increased severity of HEV during pregnancy. Data from pregnant women inadvertently vaccinated are limited but show similar rates of adverse events as non-pregnant women, and no evident harm to newborns. Protective anti-HEV IgG antibodies are estimated to last longer after vaccination than natural infection. Accelerated vaccination appears safe and provides protective antibodies similar to a normal dosing regimen. Summary HEV239 is the most extensively studied vaccine and has been shown to be safe and effective, but more data are needed to recommend use of this vaccine on a global basis. Further studies should focus on safety and efficacy in pregnant women, and evaluate a shorter two-dose regime, which is highly warranted in outbreak situations.

Prevalence and clinical correlation of hepatitis E virus antibody in the patients’ serum samples from a tertiary care hospital in Thailand during 2015–2018

“…We reported the incidence of HEV infection in pregnant women of 11.8% (Table 7 ). Studies from China demonstrated that the anti-HEV IgM antibody's detection rate in pregnant women ranged from 0.6 to 4.11% [ 18 – 20 , 29 ]. These studies screened pregnant women during their antenatal and postpartum visits, most of which were not presented with clinical hepatitis, unlike our study.…”

Hepatitis E and Pregnancy: An Unholy Alliance Unmasked from Kashmir, India

“…The role of HEV-gt1 is increasingly being recognized in causing infection and dysregulation at the maternal–fetal interface which leads to vertical transmission and increased systemic inflammation and consequent severe maternal disease [ 187 ]. Based on HEV transplacental transmission to the fetus, Bose et al [ 188 ] studied placental HEV replication in 90 pregnant women (HEV-AVH 68 and HEV-ALF 22) and detected replicative HEV RNA and HEV RNA staining by ORF3, which correlated with fetal and maternal mortality in HEV-ALF patients.…”

Towards the Improved Accuracy of Hepatitis E Diagnosis in Vulnerable and Target Groups: A Global Perspective on the Current State of Knowledge and the Implications for Practice

“…Mothers are predisposed to increased morbidity, primarily due to the development of acute liver failure (defined as the onset of jaundice, hepatic coagulopathy, and hepatic encephalopathy), which may eventually end in maternal death [ 68 , 69 , 70 ]. Pregnancy is likely to cause suppression of T cell-mediated immunity (including suppression of CD4 cells) and increased production of steroid hormones, leading to increased virus replication [ 71 , 72 ]. Upon entering the body, the virus can be present without visible antigens in a partially enveloped phase, which enables it to hide its existence from opsonizing antibodies.…”

“…This in turn suppresses cellular immunity at the circulation interface, between embryonic tissue and the uterine lining (maternal–fetal interface) and allows the transmission of HEV. Moreover, there are reports of HEV replicating within the placenta [ 71 , 73 ]. Therefore, rapid, effective response to invasive pathogens is vital to avoid massive maternal infection and consequent fetal complications [ 67 ].…”