Increased oestradiol in hepatitis E virus‐infected pregnant women promotes viral replication

Yang, Chenchen; Wu, Yu; Bi, Yanlan; Long, Feiyan; Li, Y.; Wei, Du; Hao, Xianhui; Situ, Jianwen; Yu, Zeting; Huang, Fen

doi:10.1111/jvh.12865

Cited by 39 publications

(54 citation statements)

References 32 publications

(49 reference statements)

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“…The successful establishment provided a valuable chance to explore the underlying mechanism of HEV infection. In this study, higher viral titers were detected in the fecal and blood samples of pregnant rhesus macaques than in non-pregnant rhesus macaque; this result was consistent with the classical clinical symptoms of HEV infection in pregnant women 45 . In our previous study, we confirmed estrogen-promoting HEV replication in cells when estrogen analogs are supplied (17β-estradiol or diethylstilbestrol) 45 .…”

Section: Discussionsupporting

confidence: 87%

Vertical transmission of hepatitis E virus in pregnant rhesus macaques

Hao

et al. 2020

Sci Rep

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Hepatitis E virus (HEV) is the major pathogen of viral hepatitis. HEV causes high mortality in pregnant women. Its infection during pregnancy usually leads to fulminant hepatic failure, spontaneous abortions, premature delivery, or stillbirth. Vertical transmission of HEV has been reported, but the pathogenesis during pregnancy remains largely elusive. Pregnant rhesus macaques were infected with HEV to explore the pathogenesis of genotype 4 HEV infection during pregnancy. Active HEV infections were established with shedding viruses in the feces and blood, and elevated liver enzymes. Notably, higher viral titers and longer durations of HEV infection were found in HEV-infected pregnant rhesus macaques than in non-pregnant macaques. Premature delivery and fetal death occurred in one of the HEV-infected pregnant rhesus macaques. HEV RNA was detected in the liver, spleen, kidneys, and intestines of the dead fetus. This result strongly indicated vertical HEV transmission from mother to fetus. Maternal-transferred antibodies were observed in one of the babies with poor protection. The expressions of interferon-stimulated genes (ISGs) related to HEV infection were completely different between pregnant and non-pregnant rhesus macaques. During pregnancy, impaired innate immune responses, reduced progesterone levels, and shifts in immune states may aggravate HEV infection and result in adverse pregnancy outcomes.

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Section: Discussionsupporting

confidence: 87%

Vertical transmission of hepatitis E virus in pregnant rhesus macaques

Hao

et al. 2020

Sci Rep

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“…The levels of the three hormonal factors were found to be higher in HEV-positive pregnant FHF patients than in HEV-negative patients or controls [104]. Increased estradiol in the serum of HEV-infected pregnant women promoted viral replication [114,115], which may be associated with poor outcomes [86]. In addition, a high level of estrogen was found to be related to preterm delivery, low birth weight infants and fetal mortality through placental dysfunction in pregnant women with HEV infection [116].…”

Section: Hormonal Factorsmentioning

confidence: 99%

Hepatitis E virus infection during pregnancy

Xia

2020

Virol J

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Background: Hepatitis E virus (HEV) generally causes self-limiting viral hepatitis. However, in pregnant women, HEV infection can be severe and has been associated with up to 30% mortality in the third trimester. Additionally, HEV infection in pregnancy is also associated with high rates of preterm labor and vertical transmission. Main body: HEV is now recognized as a global health problem in both developing and industrialized countries. HEV can be transmitted via the fecal-oral route, zoonotic route, and blood transfusion route. An altered immune status, hormonal levels, and viral factors may be related to the severity of the disease. Currently, no established treatment is available for HEV in pregnant women. A Chinese vaccine has been demonstrated to be protective against HEV in the general population and seems to be safe in pregnancy; however, its safety and efficacy in a large population of pregnant women remain to be determined. Conclusion: This review summarizes the current knowledge about HEV infection during pregnancy and focuses on the epidemiology, clinical manifestations, mechanisms underlying severe liver injury, and management and prevention of HEV infection during pregnancy. Considering that HEV infection during pregnancy may result in poor outcomes, screening for and monitoring HEV infection early in pregnancy should be taken into account. In addition, a better understanding of the pathogenesis will help to develop potential treatment strategies targeting HEV infection in pregnancy.

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“…(288) Proposed factors contributing to risk in pregnancy include HEV genotype 1 (with varying replication efficiency at the maternal-fetal placenta interface), (289,290) folate or other nutritional deficiencies, (291) and immunologic changes in pregnancy. (292) Acute HEV is responsible for an estimated 3,000 stillbirths worldwide annually, (293) with fetal and neonatal mortality rates likely influenced by the severity of maternal illness. A systematic review reported the median fetal and neonatal case fatality rate of 33% (interquartile range [IQR], 19%-37%) and 8% (IQR, 3%-20%), respectively.…”

Section: Hepatitis Ementioning

confidence: 99%