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Wu J, Wang H, Xiang Z, Jiang C, Xu Y, Zhai G, Ling Z, The Chinese Consortium for the Study of Hepatitis E (CCSHE). Role of viral hepatitis in pregnancy and its triggering mechanism. J Transl Int Med 2024; 12:344-354. [PMID: 39360164 PMCID: PMC11444475 DOI: 10.2478/jtim-2024-0015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/04/2024] Open
Abstract
Hepatitis viral infection can cause severe complications, even mortality in pregnant women and their offspring. Multiple studies have shown that vertical transmission can cause viral hepatitis infections in newborns, especially in hepatitis B, C, and E. Screening for hepatitis viral infection in pregnant women is essential. Once infected, pregnant women should be given timely antiviral treatments, which could effectively alleviate the disease progression and reduce adverse outcomes. Besides, the mechanism of viral hepatitis mediating adverse pregnancy outcomes has been a hot topic. Hepatitis B virus has been found to mediate both mother- to-child and parent-child transmission. Liver injury in hepatitis C virus infection is associated with immune-mediated mechanisms, which can be regulated by hormonal factors as well. The mediating mechanism of adverse maternal and infant outcomes caused by hepatitis E virus infection is mainly related to viral replication in the placenta and changes in cytokine and estrogen. Nevertheless, the specific mechanisms related to hepatitis A virus and hepatitis D virus remain unclear, and more research is needed. This review shows that the existence of viral hepatitis during pregnancy can pose certain risks for pregnant women and infants, and different interventions have been used to treat pregnant women infected with viral hepatitis. It may provide deep insight into adverse pregnancy outcomes caused by viral hepatitis and give guidance on treatment.
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Affiliation(s)
- Jian Wu
- Department of Blood Transfusion, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Suzhou215008, Jiangsu Province, China
| | - Huiqing Wang
- Department of Family Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou310016, Zhejiang Province, China
| | - Ze Xiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, City, Hangzhou310003, Zhejiang Province, China
| | - Chun Jiang
- Department of Blood Transfusion, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Suzhou215008, Jiangsu Province, China
| | - Yunyang Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, City, Hangzhou310003, Zhejiang Province, China
| | - Guanghua Zhai
- Department of Blood Transfusion, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Suzhou215008, Jiangsu Province, China
| | - Zongxin Ling
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, City, Hangzhou310003, Zhejiang Province, China
| | - The Chinese Consortium for the Study of Hepatitis E (CCSHE)
- Department of Blood Transfusion, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Suzhou215008, Jiangsu Province, China
- Department of Family Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou310016, Zhejiang Province, China
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, City, Hangzhou310003, Zhejiang Province, China
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Orosz L, Sárvári KP, Dernovics Á, Rosztóczy A, Megyeri K. Pathogenesis and clinical features of severe hepatitis E virus infection. World J Virol 2024; 13:91580. [PMID: 38984076 PMCID: PMC11229844 DOI: 10.5501/wjv.v13.i2.91580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 02/08/2024] [Accepted: 04/15/2024] [Indexed: 06/24/2024] Open
Abstract
The hepatitis E virus (HEV), a member of the Hepeviridae family, is a small, non-enveloped icosahedral virus divided into eight distinct genotypes (HEV-1 to HEV-8). Only genotypes 1 to 4 are known to cause diseases in humans. Genotypes 1 and 2 commonly spread via fecal-oral transmission, often through the consumption of contaminated water. Genotypes 3 and 4 are known to infect pigs, deer, and wild boars, often transferring to humans through inadequately cooked meat. Acute hepatitis caused by HEV in healthy individuals is mostly asymptomatic or associated with minor symptoms, such as jaundice. However, in immunosuppressed individuals, the disease can progress to chronic hepatitis and even escalate to cirrhosis. For pregnant women, an HEV infection can cause fulminant liver failure, with a potential mortality rate of 25%. Mortality rates also rise amongst cirrhotic patients when they contract an acute HEV infection, which can even trigger acute-on-chronic liver failure if layered onto pre-existing chronic liver disease. As the prevalence of HEV infection continues to rise worldwide, highlighting the particular risks associated with severe HEV infection is of major medical interest. This text offers a brief summary of the characteristics of hepatitis developed by patient groups at an elevated risk of severe HEV infection.
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Affiliation(s)
- László Orosz
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
| | - Károly Péter Sárvári
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
| | - Áron Dernovics
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
| | - András Rosztóczy
- Department of Internal Medicine, Division of Gastroenterology, University of Szeged, Szeged 6725, Csongrád-Csanád, Hungary
| | - Klára Megyeri
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
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Zhao W, Xia Y, Li T, Liu H, Zhong G, Chen D, Yu W, Li Y, Huang F. Hepatitis E virus infection upregulates ING5 expression in vitro and in vivo. Acta Biochim Biophys Sin (Shanghai) 2024; 56:1365-1372. [PMID: 38877781 PMCID: PMC11532201 DOI: 10.3724/abbs.2024091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 02/20/2024] [Indexed: 06/16/2024] Open
Abstract
Hepatitis E virus (HEV) is the major pathogen of viral hepatitis. Immunocompromised individuals infected by HEV are prone to chronic hepatitis and increase the risk of hepato-cellular carcinoma (HCC). Inhibitor of growth family member 5 (ING5) is a tumor suppressor that is expressed at low levels in cancer tumors or cells. However, the underlying relationship between ING5 and HEV infection is unclear. In the present study, acute and chronic HEV animal models are used to explore the interaction between ING5 and HEV. Notably, the expression of ING5 is significantly increased in both the livers of acute HEV-infected BALB/c mice and chronic HEV-infected rhesus macaques. In addition, the relationship between HEV infection and ING5 expression is further identified in human hepatoma (HepG-2) cells. In conclusion, HEV infection strongly upregulates ING5 expression both in vivo and in vitro, which has significant implications for further understanding the pathogenic mechanism of HEV infection.
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Affiliation(s)
- Wanqiu Zhao
- Medical FacultyKunming University of Science and TechnologyKunming650500China
| | - Yueping Xia
- Medical FacultyKunming University of Science and TechnologyKunming650500China
| | - Tengyuan Li
- Medical FacultyKunming University of Science and TechnologyKunming650500China
| | - Huichan Liu
- Medical FacultyKunming University of Science and TechnologyKunming650500China
| | - Guo Zhong
- Medical FacultyKunming University of Science and TechnologyKunming650500China
| | - Dongxue Chen
- Medical FacultyKunming University of Science and TechnologyKunming650500China
| | - Wenhai Yu
- Institute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeKunming650038China
| | - Yunlong Li
- Medical FacultyKunming University of Science and TechnologyKunming650500China
- Yunnan Provincial Key Laboratory of Clinical VirologyKunming650032China
| | - Fen Huang
- Medical FacultyKunming University of Science and TechnologyKunming650500China
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Qian Z, Cong C, Li Y, Bi Y, He Q, Li T, Xia Y, Xu L, Mickael HK, Yu W, Liu J, Wei D, Huang F. Quantification of host proteomic responses to genotype 4 hepatitis E virus replication facilitated by pregnancy serum. Virol J 2023; 20:111. [PMID: 37264422 PMCID: PMC10233519 DOI: 10.1186/s12985-023-02080-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 05/23/2023] [Indexed: 06/03/2023] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) infection is a common cause of acute hepatitis worldwide and causes approximately 30% case fatality rate among pregnant women. Pregnancy serum (PS), which contains a high concentration of estradiol, facilitates HEV replication in vitro through the suppression of the PI3K-AKT-mTOR and cAMPK-PKA-CREB signaling pathways. However, the proteomics of the complex host responses to HEV infection, especially how PS facilitates viral replication, remains unclear. METHODS In this study, the differences in the proteomics of HEV-infected HepG2 cells supplemented with fetal bovine serum (FBS) from those of HEV-infected HepG2 cells supplemented with serum from women in their third trimester of pregnancy were quantified by using isobaric tags for relative and absolute quantification technology. RESULTS A total of 1511 proteins were identified, among which 548 were defined as differentially expressed proteins (DEPs). HEV-infected cells supplemented with PS exhibited the most significant changes at the protein level. A total of 328 DEPs, including 66 up-regulated and 262 down-regulated proteins, were identified in HEV-infected cells supplemented with FBS, whereas 264 DEPs, including 201 up-regulated and 63 down-regulated proteins, were found in HEV-infected cells supplemented with PS. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that in HEV-infected cells, PS supplementation adjusted more host genes and signaling pathways than FBS supplementation. The DEPs involved in virus-host interaction participated in complex interactions, especially a large number of immune-related protein emerged in HEV-infected cells supplemented with PS. Three significant or interesting proteins, including filamin-A, thioredoxin, and cytochrome c, in HEV-infected cells were functionally verified. CONCLUSIONS The results of this study provide new and comprehensive insight for exploring virus-host interactions and will benefit future studies on the pathogenesis of HEV in pregnant women.
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Affiliation(s)
- Zhongyao Qian
- Medical School, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Chao Cong
- Medical School, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Yi Li
- Medical School, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Yanhong Bi
- Medical School, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Qiuxia He
- Medical School, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Tengyuan Li
- Medical School, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Yueping Xia
- Medical School, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Liangheng Xu
- Medical School, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Houfack K Mickael
- Medical School, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Wenhai Yu
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, People's Republic of China.
| | - Jiankun Liu
- 920th Hospital of Joint Logistics Support Force of PLA, Kunming, People's Republic of China.
| | - Daqiao Wei
- Medical School, Kunming University of Science and Technology, Kunming, People's Republic of China.
| | - Fen Huang
- Medical School, Kunming University of Science and Technology, Kunming, People's Republic of China.
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Yang J, Yuan X, Hao Y, Shi X, Yang X, Yan W, Chen L, Zhang D, Shen C, Li D, Zhu Z, Liu X, Zheng H, Zhang K. Proteins in pregnant swine serum promote the African swine fever virus replication: an iTRAQ-based quantitative proteomic analysis. Virol J 2023; 20:54. [PMID: 36978180 PMCID: PMC10043535 DOI: 10.1186/s12985-023-02004-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 03/03/2023] [Indexed: 03/30/2023] Open
Abstract
African swine fever (ASF) is a severe infectious disease caused by the African swine fever virus (ASFV), seriously endangering the global pig industry. ASFV possesses a large genome, strong mutation ability, and complex immune escape mechanisms. Since the first case of ASF was reported in China in August 2018, it has had a significant impact on social economy and food safety. In the present study, pregnant swine serum (PSS) was found to promote viral replication; differentially expressed proteins (DEPs) in PSS were screened and identified using the isobaric tags for relative and absolute quantitation technology and compared with those in non-pregnant swine serum (NPSS). The DEPs were analyzed using Gene Ontology functional annotation, Kyoto Protocol Encyclopedia of Genes and Genome pathway enrichment, and protein-protein interaction networks. In addition, the DEPs were validated via western blot and RT-qPCR experiments. And the 342 of DEPs were identified in bone marrow-derived macrophages cultured with PSS compared with the NPSS. The 256 were upregulated and 86 of DEPs were downregulated. The primary biological functions of these DEPs involved signaling pathways that regulate cellular immune responses, growth cycles, and metabolism-related pathways. An overexpression experiment showed that the PCNA could promote ASFV replication whereas MASP1 and BST2 could inhibit it. These results further indicated that some protein molecules in PSS were involved in the regulation of ASFV replication. In the present study, the role of PSS in ASFV replication was analyzed using proteomics, and the study will be provided a basis for future detailed research on the pathogenic mechanism and host interactions of ASFV as well as new insights for the development of small-molecule compounds to inhibit ASFV.
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Affiliation(s)
- Jinke Yang
- State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China
| | - Xingguo Yuan
- State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China
| | - Yu Hao
- State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China
| | - Xijuan Shi
- State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China
| | - Xing Yang
- State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China
| | - Wenqian Yan
- State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China
| | - Lingling Chen
- State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China
| | - Dajun Zhang
- State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China
| | - Chaochao Shen
- State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China
| | - Dan Li
- State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China
| | - Zixiang Zhu
- State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China
| | - Xiangtao Liu
- State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China
| | - Haixue Zheng
- State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China.
| | - Keshan Zhang
- State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730000, China.
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Xia Y, Yang W, Li Y, Qian Z, Chen S, Zhang Y, Cong C, Li T, Liu H, Chen D, Zhao W, Zhong G, Wei D, Yu W, Huang F. Severe maternal-fetal pathological damage and inflammatory responses contribute to miscarriage caused by hepatitis E viral infection during pregnancy. Liver Int 2023; 43:317-328. [PMID: 36305303 DOI: 10.1111/liv.15468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Revised: 09/04/2022] [Accepted: 10/25/2022] [Indexed: 01/28/2023]
Abstract
BACKGROUND Hepatitis E virus (HEV) infection causes serious adverse pregnancy outcomes during pregnancy. However, the maternal and fetal damage induced by HEV infection is rarely reported. METHODS A BALB/c pregnant mouse model was established to explore the maternal and fetal pathological damage and inflammatory responses caused by HEV infection. RESULTS Notably, miscarriages and stillbirths were observed in HEV-infected pregnant mice. HEV infections were identified by qRT-PCR, immunohistochemical analysis and immunofluorescence assay in the uterus, placenta, umbilical cords and livers and brains of fetuses. Serious inflammatory responses and pathological damage were triggered in the uterus and placenta of HEV-infected pregnant mice. Vertical transmission of HEV resulted in severe pathological damage and inflammatory responses in the livers and brains of fetuses, as well as emerging apoptosis cells in the brains of fetuses. Most of the cytokines/chemokines in the sera were significantly increased in the HEV-infected pregnant mice. Remarkably, cytokines/chemokines were significantly different between HEV-infected pregnant and miscarriage mice; IL9, GM-CSF and IL1α were the most important three cytokines/chemokines in determining the pregnancy outcomes. CONCLUSION HEV infections cause serious maternal/fetal pathological damage, inflammatory responses and apoptosis, which may be responsible for adverse pregnancy outcomes.
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Affiliation(s)
- Yueping Xia
- Life Science and Technology & Medical Faculty, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Weimin Yang
- Life Science and Technology & Medical Faculty, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Yi Li
- Life Science and Technology & Medical Faculty, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Zhongyao Qian
- Life Science and Technology & Medical Faculty, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Shuangfeng Chen
- Life Science and Technology & Medical Faculty, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Yike Zhang
- Life Science and Technology & Medical Faculty, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Chao Cong
- Life Science and Technology & Medical Faculty, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Tengyuan Li
- Life Science and Technology & Medical Faculty, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Huichan Liu
- Life Science and Technology & Medical Faculty, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Dongxue Chen
- Life Science and Technology & Medical Faculty, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Wanqiu Zhao
- Life Science and Technology & Medical Faculty, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Guo Zhong
- Life Science and Technology & Medical Faculty, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Daqiao Wei
- Life Science and Technology & Medical Faculty, Kunming University of Science and Technology, Kunming, People's Republic of China
| | - Wenhai Yu
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, People's Republic of China
| | - Fen Huang
- Life Science and Technology & Medical Faculty, Kunming University of Science and Technology, Kunming, People's Republic of China.,Yunnan Provincial Key Laboratory of Clinical Virology, Kunming, People's Republic of China
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Prevalence of hepatitis E virus and its association with adverse pregnancy outcomes in pregnant women in China. J Clin Virol 2023; 158:105353. [PMID: 36527809 DOI: 10.1016/j.jcv.2022.105353] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 09/12/2022] [Accepted: 12/07/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatitis E virus (HEV) infection has become a global concern, especially in pregnant women. However, the association between HEV prevalence and age, gravidity and parity of pregnant women remains unclear. METHODS Pregnant women (n=19,762) were enrolled for HEV prevalence and associated adverse pregnancy outcomes investigation in Qujing City, Yunnan Province of China from May 2019 to December 2020. RESULTS The seroprevalence of HEV was 11.6% (2,297/19,762; 95% CI:11.2%-12.1%). About 11.4% (2,247/19,762; 95% CI:10.9%-11.8%) were positive for anti-HEV IgG antibody, 0.1% (22/19,762; 95% CI:0.1%-0.2%) were positive for anti-HEV IgM antibody, and 0.1% (28/19,762; 95% CI:0.1%-0.2%) were positive for both anti-HEV IgM and IgG antibodies. Sixty-one out of 2,297 anti-HEV-antibodies-positive pregnant women were positive for HEV RNA. Phylogenetic analysis revealed that all HEV isolates from pregnant women belong to genotype 4. Age, gravidity and parity are associated with increased prevalence of HEV. Pregnant women positive for HEV-IgG antibody bear a higher risk for an adverse pregnancy history and liver injury with elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels than anti-HEV-negative pregnant women. Furthermore, seropositive pregnant women suffered a higher adverse maternal outcomes risk (crude odds ratio [cOR]=1.29; 95% CI: 1.16-1.43; adjusted odds ratio [aOR]=1.40, 95% CI: 1.25-1.55 for anti-HEV-IgG-positive pregnant women and cOR=1.38, 95% CI: 1.02-1.86; aOR=1.43, 95% CI: 1.05-1.95 for anti-HEV-IgM-positive pregnant women) and fetal outcomes risk (cOR=1.80, 95% CI: 1.61-2.01; aOR=1.77, 95% CI: 1.57-1.99) than anti-HEV-negative pregnant women. Adverse pregnancy outcomes of HEV infection are aggravated by age, gravidity and parity. CONCLUSION In this study, we demonstrated high prevalence of HEV in pregnancy women in China, and HEV infection can cause various adverse maternal and neonatal outcomes.
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Uterine Injury Caused by Genotype 4 Hepatitis E Virus Infection Based on a BALB/c Mice Model. Viruses 2021; 13:v13101950. [PMID: 34696377 PMCID: PMC8538062 DOI: 10.3390/v13101950] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 09/15/2021] [Accepted: 09/23/2021] [Indexed: 11/16/2022] Open
Abstract
To evaluate whether uterine injury caused by hepatitis E virus (HEV) infection is responsible for adverse pregnancy outcomes. HEV-infected female BALB/c mice were coupled with healthy male BALB/c mice at 0, 7, 14, 21, and 91 dpi to explore the uterine injury caused by HEV infection. Mice were euthanized after 10 days of copulation, and uteruses were collected for HEV RNA and antigen detection and histopathological analysis. Inflammatory responses; apoptosis; and estrogen receptor ɑ (ER-ɑ), endomethal antibody (ERAb), cytokeratin-7 (CK7), vimentin (VIM), and vascular endothelial growth factor (VEGF) expression levels were evaluated. After 10 days of copulation, miscarriage and nonpregnancy, as well as enlarged uteruses filled with inflammatory cytokines, were found in HEV-infected mice. HEV RNA and antigens were detected in the sera and uteruses of HEV-infected mice. Significant endometrial thickness (EMT) thinning, severe inflammatory responses, and aggravated apoptosis in the uteruses of HEV-infected mice that experienced miscarriage might contribute to adverse pregnancy outcomes. Furthermore, significantly suppressed ER-ɑ expression and increased ERAb, CK7, VIM, and VEGF expression levels were found in the uteruses of HEV-infected mice that had miscarried. However, uterine damage recovered after complete HEV clearance, and impaired fertility was improved. EMT injury, severe inflammatory responses, and aggravated apoptosis in the uterus caused by HEV infection are responsible for poor pregnancy outcomes.
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9
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Yadav KK, Kenney SP. Hepatitis E Virus Immunopathogenesis. Pathogens 2021; 10:pathogens10091180. [PMID: 34578211 PMCID: PMC8465319 DOI: 10.3390/pathogens10091180] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 09/05/2021] [Accepted: 09/06/2021] [Indexed: 12/22/2022] Open
Abstract
Hepatitis E virus is an important emerging pathogen producing a lethal impact on the pregnant population and immunocompromised patients. Starting in 1983, it has been described as the cause for acute hepatitis transmitted via the fecal–oral route. However, zoonotic and blood transfusion transmission of HEV have been reported in the past few decades, leading to the detailed research of HEV pathogenesis. The reason behind HEV being highly virulent to the pregnant population particularly during the third trimester, leading to maternal and fetal death, remains unknown. Various host factors (immunological, nutritional, hormonal) and viral factors have been studied to define the key determinants assisting HEV to be virulent in pregnant and immunocompromised patients. Similarly, chronic hepatitis is seen particularly in solid organ transplant patients, resulting in fatal conditions. This review describes recent advances in the immunopathophysiology of HEV infections in general, pregnant, and immunocompromised populations, and further elucidates the in vitro and in vivo models utilized to understand HEV pathogenesis.
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10
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Yu W, Ji H, Long F, Chen S, He Q, Xia Y, Cong C, Yang C, Wei D, Huang F. Inhibition of hepatitis E virus replication by zinc-finger antiviral Protein synergizes with IFN-β. J Viral Hepat 2021; 28:1219-1229. [PMID: 33894039 DOI: 10.1111/jvh.13522] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 04/06/2021] [Accepted: 04/08/2021] [Indexed: 01/26/2023]
Abstract
Hepatitis E virus (HEV) infection is the most common cause of acute viral hepatitis worldwide. However, host-HEV interactions have yet to be fully understood. Zinc-finger antiviral protein (ZAP) is a novel interferon (IFN)-stimulated gene product that inhibits a variety of viruses in synergy with IFN-β. To evaluate the role of ZAP in HEV infection, its expressions in HEV-infected patients and in cell cultures were measured. We report a significant inhibition of ZAP expression in patients with HEV genotype four acute infection. The expression of ZAP in the HEV life cycle was monitored in cultures of HEV-infected cells. Results indicated that the ZAP level decreased significantly after HEV infection. ZAP over-expression inhibited HEV replication, whereas its knockdown by RNA interference significantly increased HEV RNA. These suggest that ZAP serves as an antiviral in HEV infection. Moreover, silencing ZAP decreased IFN regulatory factor 3 (IRF3) phosphorylation in HEV-infected cells treated with poly(I:C), indicating that ZAP synergizes with IFN-β. In conclusion, ZAP is an important anti-HEV host factor and in synergy with IFN-β, inhibits HEV replication.
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Affiliation(s)
- Wenhai Yu
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
| | - Hanbin Ji
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Feiyan Long
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Shuangfeng Chen
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Qiuxia He
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Yueping Xia
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Chao Cong
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Chenchen Yang
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Daqiao Wei
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Fen Huang
- Medical Faculty, Kunming University of Science and Technology, Kunming, China.,Yunnan Provincial Key Laboratory of Clinical Virology, Kunming, China
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11
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Khuroo MS. Hepatitis E and Pregnancy: An Unholy Alliance Unmasked from Kashmir, India. Viruses 2021; 13:1329. [PMID: 34372535 PMCID: PMC8310059 DOI: 10.3390/v13071329] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 06/22/2021] [Accepted: 07/05/2021] [Indexed: 12/23/2022] Open
Abstract
The adverse relationship between viral hepatitis and pregnancy in developing countries had been interpreted as a reflection of retrospectively biased hospital-based data collection by the West. However, the discovery of hepatitis E virus (HEV) as the etiological agent of an epidemic of non-A, non-B hepatitis in Kashmir, and the documenting of the increased incidence and severity of hepatitis E in pregnancy via a house-to-house survey, unmasked this unholy alliance. In the Hepeviridae family, HEV-genotype (gt)1 from genus Orthohepevirus A has a unique open reading frame (ORF)4-encoded protein which enhances viral polymerase activity and viral replication. The epidemics caused by HEV-gt1, but not any other Orthohepevirus A genotype, show an adverse relationship with pregnancy in humans. The pathogenesis of the association is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the pregnant women including infection and damage to the maternal-fetal interface by HEV-gt1; vertical transmission of HEV to fetus causing severe fetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the pregnant women, promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of acute liver failure. (ALF). Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.
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Affiliation(s)
- Mohammad Sultan Khuroo
- Digestive Diseases Centre, Dr. Khuroo's Medical Clinic, Srinagar, Jammu and Kashmir 190010, India
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12
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Ji H, Chen S, He Q, Wang W, Gong S, Qian Z, Zhang Y, Wei D, Yu W, Huang F. The different replication between nonenveloped and quasi-enveloped hepatitis E virus. J Med Virol 2021; 93:6267-6277. [PMID: 34076903 DOI: 10.1002/jmv.27121] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Accepted: 05/31/2021] [Indexed: 12/15/2022]
Abstract
Hepatitis E virus (HEV) is the major pathogen of viral hepatitis. However, the understanding of the HEV life cycle is limited. In the present study, cells were separately infected with nonenveloped HEV (derived from feces or bile) or quasi-enveloped HEV (derived from the cell culture after serial passages, eHEV) and observed by confocal fluorescence microscopy to investigate the life cycle of HEV. HEV finished its binding and entry into host cells at first 6 h postinoculation (hpi). Cells inoculated with eHEV showed less infectivity than cells inoculated with nonenveloped HEV. Newly synthesized progeny virions were released into the supernatant of cell cultures from 48 hpi. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis results showed that the supernatant's progeny viruses were infectious even after five serial passages. These results show the significant difference between nonenveloped HEV and eHEV, which will provide novel insights into the HEV replication cycle. The efficient cell culture of HEV will promote the development of anti-HEV drugs and vaccines.
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Affiliation(s)
- Hanbin Ji
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Shuangfeng Chen
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Qiuxia He
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Wenjing Wang
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Shilin Gong
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Zhongyao Qian
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Yike Zhang
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Daqiao Wei
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China
| | - Wenhai Yu
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, PR China
| | - Fen Huang
- Medical Faculty, Kunming University of Science and Technology, Kunming, PR China.,Yunnan Provincial Key Laboratory of Clinical Virology, Kunming, PR China
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13
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Gong S, Hao X, Bi Y, Yang C, Wang W, Mickael HK, Zhang Y, Chen S, Qian Z, Huang F, Wei D, Yu W. Hepatitis E viral infection regulates estrogen signaling pathways: Inhibition of the cAMPK-PKA-CREB and PI3K-AKT-mTOR signaling pathways. J Med Virol 2021; 93:3769-3778. [PMID: 33128390 DOI: 10.1002/jmv.26641] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 10/17/2020] [Accepted: 10/25/2020] [Indexed: 12/22/2022]
Abstract
Hepatitis E virus (HEV) infection has become a global concern with high mortality rates among pregnant women, especially those in their third trimester of pregnancy. Estrogen plays an important role in mediating the body, regulating physiological and pathological processes. Estrogen is activated by binding to estrogen receptors (ERs) and mediates rapid signaling events by pathways that involve transmembrane ERs. Our previous study had confirmed that high estrogen levels during pregnancy are associated with high HEV titers. However, the association between HEV infection and estrogen signaling pathways remains unclear. In the present study, the regulation of estrogen signaling pathways by HEV infection was evaluated. Results demonstrated that HEV infection significantly inhibits the cAMP-PKA-CREB and PI3K-AKT-mTOR signaling pathways, but is independent of the Ras-Raf-MEK-ERK signaling pathway. In summary, the increasing estrogen levels and highly activated ERα during pregnancy aggravates HEV replication. The exacerbation of HEV replication, in turn, inhibits ERα expression and suppresses both cAMP-PKA-CREB and PI3K-AKT-mTOR signaling pathways.
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Affiliation(s)
- Shilin Gong
- Medical School, Kunming University of Science and Technology, Kunming, PR China
- Yunnan Provincial Key Laboratory of Clinical Virology, Kunming, PR China
| | - Xianhui Hao
- Medical School, Kunming University of Science and Technology, Kunming, PR China
| | - Yanhong Bi
- Medical School, Kunming University of Science and Technology, Kunming, PR China
| | - Chenchen Yang
- Medical School, Kunming University of Science and Technology, Kunming, PR China
| | - Wenjing Wang
- Medical School, Kunming University of Science and Technology, Kunming, PR China
| | - Houfack K Mickael
- Medical School, Kunming University of Science and Technology, Kunming, PR China
| | - Yike Zhang
- Medical School, Kunming University of Science and Technology, Kunming, PR China
| | - Shuangfeng Chen
- Medical School, Kunming University of Science and Technology, Kunming, PR China
| | - Zhongyao Qian
- Medical School, Kunming University of Science and Technology, Kunming, PR China
| | - Fen Huang
- Medical School, Kunming University of Science and Technology, Kunming, PR China
- Yunnan Provincial Key Laboratory of Clinical Virology, Kunming, PR China
| | - Daqiao Wei
- Medical School, Kunming University of Science and Technology, Kunming, PR China
| | - Wenhai Yu
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, PR China
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14
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Belei O, Ancusa O, Mara A, Olariu L, Amaricai E, Folescu R, Zamfir CL, Gurgus D, Motoc AG, Stânga LC, Strat L, Marginean O. Current Paradigm of Hepatitis E Virus Among Pediatric and Adult Patients. Front Pediatr 2021; 9:721918. [PMID: 34660485 PMCID: PMC8515027 DOI: 10.3389/fped.2021.721918] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 08/31/2021] [Indexed: 12/26/2022] Open
Abstract
Hepatitis E virus (HEV) infection is a polymorphic condition, present throughout the world and involving children and adults. Multiple studies over the last decade have contributed to a better understanding of the natural evolution of this infection in various population groups, several reservoirs and transmission routes being identified. To date, acute or chronic HEV-induced hepatitis has in some cases remained underdiagnosed due to the lower accuracy of serological tests and due to the evolutionary possibility with extrahepatic manifestations. Implementation of diagnostic tests based on nucleic acid analysis has increased the detection rate of this disease. The epidemiological and clinical features of HEV hepatitis differ depending on the geographical areas studied. HEV infection is usually a self-limiting condition in immunocompetent patients, but in certain categories of vulnerable patients it can induce a sudden evolution toward acute liver failure (pregnant women) or chronicity (immunosuppressed patients, post-transplant, hematological, or malignant diseases). In acute HEV infections in most cases supportive treatment is sufficient. In patients who develop chronic hepatitis with HEV, dose reduction of immunosuppressive medication should be the first therapeutic step, especially in patients with transplant. In case of unfavorable response, the initiation of antiviral therapy is recommended. In this review, the authors summarized the essential published data related to the epidemiological, clinical, paraclinical, and therapeutic aspects of HEV infection in adult and pediatric patients.
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Affiliation(s)
- Oana Belei
- First Pediatric Clinic, Disturbance of Growth and Development on Children Research Center, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Oana Ancusa
- Fifth Department of Internal Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Adelina Mara
- Department of Internal Medicine, Emergency City Hospital, Timisoara, Romania
| | - Laura Olariu
- First Pediatric Clinic, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Elena Amaricai
- Department of Rehabilitation Physical Medicine and Rheumatology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Roxana Folescu
- Department of Balneology, Medical Recovery and Rheumatology, Family Discipline, Center for Preventive Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Carmen Lacramioara Zamfir
- Department of Morpho-Functional Sciences I, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Daniela Gurgus
- Department of Balneology, Medical Recovery and Rheumatology, Family Discipline, Center for Preventive Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Andrei G Motoc
- Department of Anatomy and Embriology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Livia Claudia Stânga
- Department of Microbiology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Liliana Strat
- Department of Mother and Child Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Otilia Marginean
- First Pediatric Clinic, Disturbance of Growth and Development on Children Research Center, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
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15
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Aslan AT, Balaban HY. Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment. World J Gastroenterol 2020; 26:5543-5560. [PMID: 33071523 PMCID: PMC7545399 DOI: 10.3748/wjg.v26.i37.5543] [Citation(s) in RCA: 107] [Impact Index Per Article: 21.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 08/11/2020] [Accepted: 09/09/2020] [Indexed: 02/06/2023] Open
Abstract
The hepatitis E virus (HEV) is the fifth known form of viral hepatitis and was first recognized as the cause of an epidemic of unexplained acute hepatitis in the early 1980s. Globally, it is one of the most frequent causes of acute viral hepatitis. The majority of HEV infections are asymptomatic and lead to the spontaneous clearance of the virus. Among the eight different genotypes identified to date, HEV genotype 1 (HEV1), HEV2, HEV3, and HEV4 are the most frequent genotypes causing infections in humans. HEV1 and HEV2 are prevalent in developing regions and able to result in large-scale outbreaks originating from contaminated water supplies. They are also responsible for severe hepatitis in pregnant patients and infants. In contrast, HEV3 and HEV4 are zoonotic, and the transmission of these genotypes to humans occurs mainly through the fecal contamination of water and consumption of contaminated meat from infected animals. Their main reservoir is the pig, and they are mostly encountered in developed countries. The major risk groups for HEV infection and its ensuing adverse consequences are pregnant women, infants, older people, immunocompromised individuals, patients with underlying chronic liver diseases, and workers that come into close contact with HEV-infected animals. In the clinical perspective, HEV infections have diverse clinical manifestations including acute and self-limiting hepatitis, acute-on-chronic liver disease, chronic hepatitis, cirrhosis, and liver failure. Although HEV mainly results in acute self-limiting infection, chronic HEV infection may occur among immunocompromised patients (e.g., solid-organ transplant recipients). Additionally, HEV-associated extrahepatic manifestations involving various organs have been reported in the last decade, although the causal link for many of them still needs to be proven. Ribavirin and interferon-alpha are the most widely used agents for the treatment of HEV infections with a certain level of success. However, ribavirin is contraindicated in pregnant patients, and interferon-alpha cannot be used in most transplant recipients. Therefore, there is an urgent need for novel antiviral compounds that are safe and effective particularly for patients having contraindications for ribavirin or interferon-alpha and infected by the ribavirin-resistant HEV. In this review article, a literature search using PubMed and MEDLINE databases was performed, up to March 2020. Only the articles published in English were reviewed.
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Affiliation(s)
| | - Hatice Yasemin Balaban
- Department of Gastroenterology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey
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16
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Abstract
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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Affiliation(s)
- Chunchen Wu
- Department of Laboratory Medicine, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People's Republic of China
| | - Xiaoxue Wu
- Department of Laboratory Medicine, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People's Republic of China
| | - Jianbo Xia
- Department of Laboratory Medicine, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People's Republic of China.
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17
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Lhomme S, Marion O, Abravanel F, Izopet J, Kamar N. Clinical Manifestations, Pathogenesis and Treatment of Hepatitis E Virus Infections. J Clin Med 2020; 9:E331. [PMID: 31991629 PMCID: PMC7073673 DOI: 10.3390/jcm9020331] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 01/14/2020] [Accepted: 01/22/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis throughout the world. Most infections are acute but they can become chronic in immunocompromised patients, such as solid organ transplant patients, patients with hematologic malignancy undergoing chemotherapy and those with a human immunodeficiency virus (HIV) infection. Extra-hepatic manifestations, especially neurological and renal diseases, have also been described. To date, four main genotypes of HEV (HEV1-4) were described. HEV1 and HEV2 only infect humans, while HEV3 and HEV4 can infect both humans and animals, like pigs, wild boar, deer and rabbits. The real epidemiology of HEV has been underestimated because most infections are asymptomatic. This review focuses on the recent advances in our understanding of the pathophysiology of acute HEV infections, including severe hepatitis in patients with pre-existing liver disease and pregnant women. It also examines the mechanisms leading to chronic infection in immunocompromised patients and extra-hepatic manifestations. Acute infections are usually self-limiting and do not require antiviral treatment. Conversely, a chronic HEV infection can be cleared by decreasing the dose of immunosuppressive drugs or by treating with ribavirin for 3 months. Nevertheless, new drugs are needed for those cases in which ribavirin treatment fails.
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Affiliation(s)
- Sébastien Lhomme
- Virology Laboratory, National Reference Center for Hepatitis E Virus, Toulouse Purpan University Hospital, 31300 Toulouse, France; (F.A.); (J.I.)
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
| | - Olivier Marion
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
- Department of Nephrology and Organs Transplantation, Toulouse Rangueil University Hospital, 31400 Toulouse, France
| | - Florence Abravanel
- Virology Laboratory, National Reference Center for Hepatitis E Virus, Toulouse Purpan University Hospital, 31300 Toulouse, France; (F.A.); (J.I.)
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
| | - Jacques Izopet
- Virology Laboratory, National Reference Center for Hepatitis E Virus, Toulouse Purpan University Hospital, 31300 Toulouse, France; (F.A.); (J.I.)
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
| | - Nassim Kamar
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
- Department of Nephrology and Organs Transplantation, Toulouse Rangueil University Hospital, 31400 Toulouse, France
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18
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Aggarwal R, Goel A. Natural History, Clinical Manifestations, and Pathogenesis of Hepatitis E Virus Genotype 1 and 2 Infections. Cold Spring Harb Perspect Med 2019; 9:a032136. [PMID: 29735580 PMCID: PMC6601454 DOI: 10.1101/cshperspect.a032136] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Infection with genotype 1 or 2 hepatitis E virus (HEV) results primarily from human-to-human transmission through the fecal-oral route in low-resource countries. It presents primarily as "acute viral hepatitis" syndrome, usually a self-limiting illness. A few cases progress to acute liver failure, a serious illness with high fatality. Clinical disease is infrequent among children. Infection during pregnancy is associated with a higher risk of symptomatic disease, severe liver injury, and mortality. Severe disease is also encountered in persons with preexisting chronic liver disease. Some cases have associated extrahepatic features, particularly acute pancreatitis and neurological manifestations. Chronic infection appears to be extremely infrequent with these HEV genotypes. The exact pathogenesis of liver injury remains unknown, although the host immune response appears to be important for viral clearance as well as for induction of liver injury. Hormonal and immune factors appear to be responsible for the severe disease during pregnancy.
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Affiliation(s)
- Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Amit Goel
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
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19
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Yang C, Hao X, Li Y, Long F, He Q, Huang F, Yu W. Successful Establishment of Hepatitis E Virus Infection in Pregnant BALB/c Mice. Viruses 2019; 11:E451. [PMID: 31108901 PMCID: PMC6563234 DOI: 10.3390/v11050451] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 05/08/2019] [Accepted: 05/14/2019] [Indexed: 02/06/2023] Open
Abstract
Worldwide, the Hepatitis E virus (HEV) is the main pathogen of acute viral hepatitis, with an extremely high mortality in pregnant women. However, the pathogenesis of HEV infection in pregnant women remains largely unknown. We established an HEV-infected pregnant mice animal model to explore the adverse pregnancy outcomes of HEV infection. Mice were infected with HEV in their early, middle and late stages of pregnancy. HEV RNA was detected in the tissues (liver, spleen, kidney, colon, uterus and placenta) of pregnant mice. HEV antigens were also detected in these tissues of HEV-infected pregnant mice. Miscarriages (7/8, 87.5%) occurred in pregnant mice infected with HEV in the middle of pregnancy. Th1-biased immune status was found in these aborted mice. Vertical transmission was confirmed by HEV replication in the uterus and placenta, as well as in the positive HEV RNA and HEV antigen positive in fetal livers. The successful establishment of HEV infection in pregnant mice is beneficial for further study of HEV pathogenesis, especially the adverse pregnancy outcomes caused by HEV infection.
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Affiliation(s)
- Chenchen Yang
- Medical School, Kunming University of Science and Technology, Kunming 650500, China.
| | - Xianhui Hao
- Medical School, Kunming University of Science and Technology, Kunming 650500, China.
| | - Yunlong Li
- Medical School, Kunming University of Science and Technology, Kunming 650500, China.
| | - Feiyan Long
- Medical School, Kunming University of Science and Technology, Kunming 650500, China.
| | - Qiuxia He
- Medical School, Kunming University of Science and Technology, Kunming 650500, China.
| | - Fen Huang
- Medical School, Kunming University of Science and Technology, Kunming 650500, China.
| | - Wenhai Yu
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
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20
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Arora A, Kumar A, Anand AC, Puri P, Dhiman RK, Acharya SK, Aggarwal K, Aggarwal N, Aggarwal R, Chawla YK, Dixit VK, Duseja A, Eapen CE, Goswami B, Gujral K, Gupta A, Jindal A, Kar P, Kumari K, Madan K, Malhotra J, Malhotra N, Pandey G, Pandey U, Puri RD, Rai RR, Rao PN, Sarin SK, Sharma A, Sharma P, Shenoy KT, Singh KR, Singh SP, Suri V, Trehanpati N, Wadhawan M. Indian National Association for the Study of the Liver-Federation of Obstetric and Gynaecological Societies of India Position Statement on Management of Liver Diseases in Pregnancy. J Clin Exp Hepatol 2019; 9:383-406. [PMID: 31360030 PMCID: PMC6637074 DOI: 10.1016/j.jceh.2019.02.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Accepted: 02/25/2019] [Indexed: 12/12/2022] Open
Abstract
Liver diseases occurring during pregnancy can be serious and can progress rapidly, affecting outcomes for both the mother and fetus. They are a common cause of concern to an obstetrician and an important reason for referral to a hepatologist, gastroenterologist, or physician. Liver diseases during pregnancy can be divided into disorders unique to pregnancy, those coincidental with pregnancy, and preexisting liver diseases exacerbated by pregnancy. A rapid differential diagnosis between liver diseases related or unrelated to pregnancy is required so that specialist and urgent management of these conditions can be carried out. Specific Indian guidelines for the management of these patients are lacking. The Indian National Association for the Study of the Liver (INASL) in association with the Federation of Obstetric and Gynaecological Societies of India (FOGSI) had set up a taskforce for development of consensus guidelines for management of patients with liver diseases during pregnancy, relevant to India. For development of these guidelines, a two-day roundtable meeting was held on 26-27 May 2018 in New Delhi, to discuss, debate, and finalize the consensus statements. Only those statements that were unanimously approved by most members of the taskforce were accepted. The primary objective of this review is to present the consensus statements approved jointly by the INASL and FOGSI for diagnosing and managing pregnant women with liver diseases. This article provides an overview of liver diseases occurring in pregnancy, an update on the key mechanisms involved in its pathogenesis, and the recommended treatment options.
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Key Words
- ABCB4, ATP-binding cassette subfamily B member 4
- AFLP, Acute fatty liver of pregnancy
- ALF, Acute liver failure
- ALP, Alkaline phosphatase
- ALT, Alanine transferase
- ART, Antiretroviral therapy
- AST, Aspartate aminotransferase
- BCS, Budd-Chiari syndrome
- CT, Computerized tomography
- DIC, Disseminated intravascular coagulation
- DNA, Deoxyribonucleic acid
- DPTA, Diethylenetriamine pentaacetic acid
- ERCP, Endoscopic retrograde cholangiopancreatography
- FDA, Food and Drug Administration
- FOGSI, Federation of Obstetric and Gynaecological Societies of India
- GGT, Gamma-glutamyl transpeptidase
- GI, Gastrointestinal
- GRADE, Grading of Recommendations Assessment Development and Evaluation
- HBIG, Hepatitis B immune globulin
- HBV, Hepatitis B virus
- HBeAg, Hepatitis B envelope antigen
- HBsAg, Hepatitis B surface antigen
- HCV, Hepatitis C virus
- HELLP syndrome
- HELLP, Hemolysis, elevated liver enzymes, low platelet count
- HG, Hyperemesis gravidarum
- HIV, Human immunodeficiency virus
- HV, Hepatic vein
- ICP, Intrahepatic cholestasis of pregnancy
- INASL, Indian National Association for the Study of Liver
- IVF, In vitro fertilization
- LFT, Liver function test
- MDR, Multidrug resistance
- MRI, Magnetic resonance imaging
- MTCT, Mother-to-child transmission
- NA, Nucleos(t)ide analog
- PIH, Pregnancy-induced hypertension
- PT, Prothrombin time
- PUQE, Pregnancy-Unique Quantification of Emesis
- PegIFN, Pegylated interferon
- RNA, Ribonucleic acid
- TAF, Tenofovir alafenamide
- TDF, Tenofovir disoproxil fumarate
- TIPS, Transjugular intrahepatic portosystemic shunt
- UDCA, Ursodeoxycholic acid
- UGI, Upper gastrointestinal
- ULN, Upper limit of normal
- acute fatty liver of pregnancy
- hyperemesis gravidarum
- intrahepatic cholestasis of pregnancy
- liver diseases in pregnancy
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Affiliation(s)
- Anil Arora
- Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Ashish Kumar
- Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Anil C. Anand
- Kalinga Institute of Medical Sciences, KIIT University, Bubaneswar, India
| | - Pankaj Puri
- Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Subrat K. Acharya
- Kalinga Institute of Medical Sciences, KIIT University, Bubaneswar, India
| | - Kiran Aggarwal
- Department of Obstetrics and Gynecology, LHMC & Associated Hospitals, New Delhi, India
| | - Neelam Aggarwal
- Department of Obstetrics and Gynecology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Yogesh K. Chawla
- Kalinga Institute of Medical Sciences, KIIT University, Bubaneswar, India
| | - Vinod K. Dixit
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Bhabadev Goswami
- Department of Gastroenterology, Guwahati Medical College, Assam, India
| | - Kanwal Gujral
- Institute of Obstetrics and Gynecology, Sir Ganga Ram Hospital, New Delhi, India
| | - Anoop Gupta
- Delhi IVF and Fertility Research Centre, New Delhi, India
| | - Ankur Jindal
- Institute of Liver and Biliary Sciences, New Delhi, India
| | - Premashish Kar
- Department of Gastroenterology and Hepatology, Max Super Speciality Hospital, Vaishali, Patparganj, New Delhi
| | - Krishna Kumari
- Max Cure Suyosha Woman & Child Hospital, Hyderabad, India
| | - Kaushal Madan
- Max Smart Super Speciality Hospital, Saket, New Delhi, India
| | | | | | - Gaurav Pandey
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Uma Pandey
- Dept of Obstetrics & Gynecology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
| | - Ratna D. Puri
- Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Ramesh R. Rai
- Department of Gastroenterology, NIMS Medical College and Hospital, Jaipur, India
| | - Padaki N. Rao
- Department of Hepatology, Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Shiv K. Sarin
- Institute of Liver and Biliary Sciences, New Delhi, India
| | - Aparna Sharma
- Department of Obstetrics and Gynecology, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Praveen Sharma
- Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Koticherry T. Shenoy
- Sree Gokulam Medical College and Research Foundation, Venjaramoodu, Thiruvananthapuram, India
| | - Karam R. Singh
- Regional Institute of Medical Sciences (RIMS), Imphal, Manipur, India
| | | | - Vanita Suri
- Department of Obstetrics and Gynecology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Singh S, Daga MK, Kumar A, Husain SA, Kar P. Role of oestrogen and its receptors in HEV-associated feto-maternal outcomes. Liver Int 2019; 39:633-639. [PMID: 29979823 DOI: 10.1111/liv.13928] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Revised: 06/15/2018] [Accepted: 07/02/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Pregnant women infected with HEV develops adverse pregnancy outcomes like, abortions, intrauterine fetal death, still births, neonatal deaths, preterm delivery and maternal mortality. AIM To correlate oestrogen and its receptors ESR1α and ESR2β levels with HEV-associated feto-maternal outcomes. MATERIAL & METHODS A total of 142 pregnant women with HEV infection and 142 pregnant controls were included in study from Department of Obstetrics & Gynaecology and Department of Medicine, Maulana Azad Medical College (MAMC) and associated Lok Nayak Hospital (LNH), New Delhi. Three millilitre of blood sample was collected in plain for quantification of oestrogen, and its receptors ESR1α and ESR2β using commercially available third-generation ELISA kits. RESULTS The levels of oestrogen, ESR1α and ESR2β were considerably higher in HEV-infected pregnant women (20.11 ± 18.19 ng/mL, 10.58 ± 3.27 ng/mL, 10.42 ± 4.71 ng/mL respectively) than pregnant controls (11.74 ± 6.42 ng/mL, 9.11 ± 1.63 ng/mL, 9.01 ± 1.18 ng/mL respectively)(P < 0.0001). It was found that oestrogen levels were significantly higher in pregnant women infected with HEV who had preterm delivery, low birth weight babies and fetal loss (19.64 ± 17.60 ng/mL, 19.71 ± 17.63 ng/mL, 33.62 ± 23.20 ng/mL respectively) than who had full term delivery, average birth weight babies and live babies (11.71 ± 8.77 ng/mL, 11.99 ± 9.44 ng/mL, 16.58 ± 14.98 ng/mL respectively)(P < 0.05). A significant negative correlation was observed between baby birth weight and oestrogen levels in HEV-infected pregnant women. CONCLUSION The high level of oestrogen plays an important role in preterm delivery, low birth weight babies and fetal mortality in pregnant women with HEV infection through placental dysfunction. Moreover, oestrogen level is a significant predictor for preterm delivery and maternal mortality and ESR2β levels is a significant predictor for maternal mortality in pregnant women infected with HEV.
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Affiliation(s)
- Swati Singh
- Department of Medicine, Maulana Azad Medical College, New Delhi, India
| | - Mradul K Daga
- Department of Medicine, Maulana Azad Medical College, New Delhi, India
| | - Ashok Kumar
- Department of Obstetrics & Gynaecology, Maulana Azad Medical College, New Delhi, India
| | - Syed A Husain
- Department of Biosciences, Jamia Millia Islamia, New Delhi, India
| | - Premashis Kar
- Department of Medicine, Maulana Azad Medical College, New Delhi, India
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22
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Yang C, Yu W, Bi Y, Long F, Li Y, Wei D, Hao X, Situ J, Zhao Y, Huang F. Increased oestradiol in hepatitis E virus-infected pregnant women promotes viral replication. J Viral Hepat 2018; 25:742-751. [PMID: 29345855 DOI: 10.1111/jvh.12865] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Accepted: 12/14/2017] [Indexed: 01/17/2023]
Abstract
Hepatitis E virus (HEV) infection causes subclinical diseases, leading to high mortality (>25%) in pregnant women. HEV replication is aggressively escalated in pregnant women, especially in the third trimester of pregnancy. Oestrogen plays an important role in pregnancy. However, the pathogenesis of HEV in pregnant women or immunosuppressive pregnant women (such as HIV-infected or organ-transplanted pregnant women) remains unclear. We investigated the role of oestradiol in HEV infection in a cell culture system. HEV-infected pregnant women had significantly higher oestradiol levels compared with uninfected individuals. HEV infection was significantly increased in cells treated with analogues of oestradiol, diethylstilbestrol (DES) or 17β-oestradiol in a dose-dependent way. However, tamoxifen, an antagonist oestrogen, inhibited HEV replication. HEV infection inhibits oestrogen receptor (ER-α) expression. Immunofluorescence and co-immunoprecipitation assays indicated that ER-α interacted with the helicase of HEV ORF1 indirectly. More importantly, HEV infection was exacerbated in immunosuppressive cells treated with an inhibitor of PI3K-AKT-mTOR signal pathway (LY296004) and supplemented with pregnant women serum with high oestradiol simultaneously. These results strongly suggest that pregnant women with high oestradiol and/or immunosuppression will be vulnerable to HEV infection.
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Affiliation(s)
- C Yang
- Medical School, Kunming University of Science and Technology, Kunming, China
| | - W Yu
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
| | - Y Bi
- Medical School, Kunming University of Science and Technology, Kunming, China
| | - F Long
- Medical School, Kunming University of Science and Technology, Kunming, China
| | - Y Li
- Medical School, Kunming University of Science and Technology, Kunming, China
| | - D Wei
- Medical School, Kunming University of Science and Technology, Kunming, China
| | - X Hao
- Medical School, Kunming University of Science and Technology, Kunming, China
| | - J Situ
- Medical School, Kunming University of Science and Technology, Kunming, China
| | - Y Zhao
- Medical School, Kunming University of Science and Technology, Kunming, China
| | - F Huang
- Medical School, Kunming University of Science and Technology, Kunming, China
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Kumar N, Das V, Agarwal A, Pandey A, Agrawal S. Fetomaternal outcomes in pregnant women with hepatitis E infection; still an important fetomaternal killer with an unresolved mystery of increased virulence in pregnancy. Turk J Obstet Gynecol 2017; 14:106-113. [PMID: 28913146 PMCID: PMC5558410 DOI: 10.4274/tjod.15045] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Accepted: 04/10/2017] [Indexed: 01/25/2023] Open
Abstract
Objective: Hepatitis is a prevalent infection in developing countries. While hepatitis B and C are deepening their roots in the developed world, hepatitis A and E are common in the developing world. The uniqueness of hepatitis is in its transformation from a relatively self-limiting disease in the non-pregnant state, to a highly virulent disease during pregnancy. Materials and Methods: This retrospective observational study was conducted in the Department of Obstetrics and Gynecology, King George’s Medical University, Lucknow, for a period of six months from June 2016 to November 2016 [probably during an endemic peak of hepatitis E virus (HEV)] to observe the clinical outcomes in HEV-infected pregnant women. Results: A total of 32 anti-HEV immunoglobulin M-positive pregnant women were included, and fetomaternal outcomes were analyzed. Hepatitis E positivity was significantly associated with maternal mortality, intrauterine demise with prematurity, and premature rupture of membranes was the most common fetal complication noted. Conclusion: The difference in extent of virulence of infection and variations in maternal morbidity, mortality, and rates of intrauterine demise, signify the presence of some factors that play a role and need to be further studied and evaluated.
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Affiliation(s)
- Namrata Kumar
- King George's Medical University, Department of Obstetrics and Gynecology, Lucknow, India
| | - Vinita Das
- King George's Medical University, Department of Obstetrics and Gynecology, Lucknow, India
| | - Anjoo Agarwal
- King George's Medical University, Department of Obstetrics and Gynecology, Lucknow, India
| | - Amita Pandey
- King George's Medical University, Department of Obstetrics and Gynecology, Lucknow, India
| | - Smriti Agrawal
- King George's Medical University, Department of Obstetrics and Gynecology, Lucknow, India
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Abstract
INTRODUCTION Infection with hepatitis E virus (HEV) is the commonest cause of acute hepatitis worldwide. HEV was discovered in 1980s and is known to have small non-enveloped virions with single-stranded RNA genome of positive polarity. In recent years. In recent years, availability of new information has changed our understanding of this virus and the pathogenesis of the related disease. AREAS COVERED This article reviews the current knowledge about structure, genomic organization, taxonomy, genetic epidemiology, host specificity and replication of the human HEV and of various closely-related viruses that infect other animals. In addition, the models available for the study of HEV infection, the available information on the pathogenesis of this infection and the techniques available for its diagnosis are also reviewed. Expert commentary: A circulating, enveloped form of the human HEV has been recently recognized. Originally believed to naturally infect only humans and possibly primates, HEV-like viruses are now known to infect several vertebrate animals. Based on this, phylogenetic classification of these viruses has recently been revised. In vitro replicons and infection systems have been developed, which have improved our understanding about the virus and the pathogenesis of infection with it. Recent development of mouse models with chimeric livers that contain human hepatocytes provides another avenue for further advancement of this knowledge.
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Affiliation(s)
- Rakesh Aggarwal
- a Department of Gastroenterology , Sanjay Gandhi Postgraduate Institute of Medical Sciences , Lucknow , India
| | - Amit Goel
- a Department of Gastroenterology , Sanjay Gandhi Postgraduate Institute of Medical Sciences , Lucknow , India
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Lhomme S, Marion O, Abravanel F, Chapuy-Regaud S, Kamar N, Izopet J. Hepatitis E Pathogenesis. Viruses 2016; 8:E212. [PMID: 27527210 PMCID: PMC4997574 DOI: 10.3390/v8080212] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 07/22/2016] [Accepted: 07/27/2016] [Indexed: 02/08/2023] Open
Abstract
Although most hepatitis E virus (HEV) infections are asymptomatic, some can be severe, causing fulminant hepatitis and extra-hepatic manifestations, including neurological and kidney injuries. Chronic HEV infections may also occur in immunocompromised patients. This review describes how our understanding of the pathogenesis of HEV infection has progressed in recent years.
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Affiliation(s)
- Sébastien Lhomme
- INSERM, UMR1043, Department of Virology, CHU Purpan, Université Paul Sabatier, 31000 Toulouse, France.
| | - Olivier Marion
- INSERM, UMR1043, Department of Virology, CHU Purpan, Université Paul Sabatier, 31000 Toulouse, France.
- INSERM, UMR1043, Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, Université Paul Sabatier, 31000 Toulouse, France.
| | - Florence Abravanel
- INSERM, UMR1043, Department of Virology, CHU Purpan, Université Paul Sabatier, 31000 Toulouse, France.
| | - Sabine Chapuy-Regaud
- INSERM, UMR1043, Department of Virology, CHU Purpan, Université Paul Sabatier, 31000 Toulouse, France.
| | - Nassim Kamar
- INSERM, UMR1043, Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, Université Paul Sabatier, 31000 Toulouse, France.
| | - Jacques Izopet
- INSERM, UMR1043, Department of Virology, CHU Purpan, Université Paul Sabatier, 31000 Toulouse, France.
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Lachish T, Erez O, Daudi N, Shouval D, Schwartz E. Acute hepatitis E virus in pregnant women in Israel and in other industrialized countries. J Clin Virol 2015; 73:20-24. [PMID: 26521225 DOI: 10.1016/j.jcv.2015.10.011] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2015] [Revised: 10/10/2015] [Accepted: 10/16/2015] [Indexed: 10/22/2022]
Abstract
BACKGROUND AND OBJECTIVES Acute hepatitis E virus (HEV) is the most common etiology of viral hepatitis in adults in developing countries. HEV is rare in industrialized countries but its incidence is rising both in returning travelers and through autochthonous infection. In developing countries HEV is associated with a high rate of fulminant hepatitis and mortality during pregnancy and contributes to poor obstetric and fetal outcomes. There are no reliable data on the outcome of HEV during pregnancy in industrialized countries. STUDY DESIGN A retrospective analysis of acute HEV cases diagnosed in Israel were examined. The clinical course of the disease among pregnant women was retrieved. A systematic review of the literature was performed for cases of HEV and pregnancy, originating or treated in industrialized countries RESULTS Between the years 1993-2013, 68 cases of acute HEV were diagnosed in Israel, including 9 pregnant women (13%). An additional 6 reported cases were found from a literature search. From the 15 women (10 autochthonous cases and 5 imported cases), the outcome was favorable in 10 cases, however, 5 cases (33%) resulted in fulminant hepatitis and two women underwent an urgent liver transplantation. No fatality occurred in the mothers and all babies were born alive and healthy. DISCUSSION This is the first case series of acute HEV infection in pregnant women in industrialized countries. Acute HEV infection poses a significant risk in pregnancy, irrespective of patients' country of origin. In contrast to reports from developing countries, all babies and mothers survived.
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Affiliation(s)
- Tamar Lachish
- The Infectious Diseases Unit, Shaare-Zedek Medical Center, Jerusalem, Israel.
| | - Ortal Erez
- The Hebrew University, Hadassah Medical School, Jerusalem, Israel.
| | - Nili Daudi
- The Liver Unit, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
| | - Daniel Shouval
- The Liver Unit, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
| | - Eli Schwartz
- The Center for Geographic Medicine and Department of Medicine C, Sheba Medical Center, Tel Hashomer and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
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