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Kanda T, Li TC, Takahashi M, Nagashima S, Primadharsini PP, Kunita S, Sasaki-Tanaka R, Inoue J, Tsuchiya A, Nakamoto S, Abe R, Fujiwara K, Yokosuka O, Suzuki R, Ishii K, Yotsuyanagi H, Okamoto H. Recent advances in hepatitis E virus research and the Japanese clinical practice guidelines for hepatitis E virus infection. Hepatol Res 2024; 54:1-30. [PMID: 38874115 DOI: 10.1111/hepr.14062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 04/22/2024] [Accepted: 05/09/2024] [Indexed: 06/15/2024]
Abstract
Acute hepatitis E was considered rare until reports emerged affirming the existence of hepatitis E virus (HEV) genotypes 3 and 4 infections in Japan in the early 2000s. Extensive studies by Japanese researchers have highlighted the pivotal role of pigs and wild animals, such as wild boars and deer, as reservoirs for HEV, linking them to zoonotic infections in Japan. Currently, when hepatitis occurs subsequent to the consumption of undercooked or grilled pork, wild boar meat, or offal (including pig liver and intestines), HEV infection should be considered. Following the approval of anti-HEV immunoglobulin A antibody as a diagnostic tool for hepatitis E by Japan's Health Insurance System in 2011, the annual number of diagnosed cases of HEV infection has surged. Notably, the occurrence of post-transfusion hepatitis E promoted nationwide screening of blood products for HEV using nucleic acid amplification tests since 2020. Furthermore, chronic hepatitis E has been observed in immunosuppressed individuals. Considering the significance of hepatitis E, heightened preventive measures are essential. The Japan Agency for Medical Research and Development Hepatitis A and E viruses (HAV and HEV) Study Group, which includes special virologists and hepatologists, held a virtual meeting on February 17, 2024. Discussions encompassed pathogenesis, transmission routes, diagnosis, complications, severity factors, and ongoing and prospective vaccination or treatments for hepatitis E. Rigorous assessment of referenced studies culminated in the formulation of recommendations, which are detailed within this review. This comprehensive review presents recent advancements in HEV research and Japanese clinical practice guidelines for HEV infection.
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Affiliation(s)
- Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
- Division of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minamiuonuma, Japan
- Division of Gastroenterology and Hepatology, Graduate School of Medicine and Dental Sciences, Niigata University, Niigata, Japan
| | - Tian-Cheng Li
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Putu Prathiwi Primadharsini
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Satoshi Kunita
- Center for Experimental Medicine, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Reina Sasaki-Tanaka
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
- Division of Gastroenterology and Hepatology, Graduate School of Medicine and Dental Sciences, Niigata University, Niigata, Japan
| | - Jun Inoue
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medicine and Dental Sciences, Niigata University, Niigata, Japan
| | - Shingo Nakamoto
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
| | - Ryuzo Abe
- Department of Emergency Medicine, Oita University, Oita, Japan
| | - Keiichi Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
| | - Ryosuke Suzuki
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Koji Ishii
- Department of Quality Assurance and Radiological Protection, National Institute of Infectious Diseases, Tokyo, Japan
| | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
- Department of Infectious Diseases and Applied Immunology, Hospital of the Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
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Ying D, Niu W, Chen Y, Wang Y, Tian W, Zhang X, Liu C, Wang S, Chen Z, Lin Y, Guo S, Yu Z, Chen X, Fang M, Qiang H, Yin Y, Tang Z, Zheng Z, Fu L, Xia N. Case Report: Chronic hepatitis E virus Infection in an individual without evidence for immune deficiency. Front Immunol 2023; 14:1183859. [PMID: 37404820 PMCID: PMC10315653 DOI: 10.3389/fimmu.2023.1183859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 05/03/2023] [Indexed: 07/06/2023] Open
Abstract
Chronic hepatitis E virus (HEV) infection occurs mainly in immunosuppressed populations. We describe an investigation of chronic HEV infection of genotype 3a in an individual without evidence for immune deficiency who presented hepatitis with significant HEV viremia and viral shedding. We monitored HEV RNA in plasma and stools, and assessed anti-HEV specific immune responses. The patient was without apparent immunodeficiency based on quantified results of white blood cell, lymphocyte, neutrophilic granulocyte, CD3+ T cell, CD4+ T cell, and CD8+ T cell counts and CD4/CD8 ratio, as well as total serum IgG, IgM, and IgA, which were in the normal range. Despite HEV specific cellular response and strong humoral immunity being observed, viral shedding persisted up to 109 IU/mL. After treatment with ribavirin combined with interferon, the indicators of liver function in the patient returned to normal, accompanied by complete suppression and clearance of HEV. These results indicate that HEV chronicity can also occur in individuals without evidence of immunodeficiency.
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Affiliation(s)
- Dong Ying
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
| | - Wenxia Niu
- Department of Infectious Disease, Xiang’an Hospital of Xiamen University, Xiamen, China
| | - Yanling Chen
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
| | - Yingbin Wang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
| | - Weikun Tian
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
| | - Xiaoping Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
| | - Chang Liu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
| | - Siling Wang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
| | - Zihao Chen
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
| | - Yajie Lin
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
| | - Shaoqi Guo
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
| | - Zihao Yu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
| | - Xiuting Chen
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
| | - Mujin Fang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
- National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, Xiamen University, Xiamen, China
| | - Hongsheng Qiang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
| | - Yifan Yin
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
| | - Zimin Tang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
- National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, Xiamen University, Xiamen, China
| | - Zizheng Zheng
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
| | - Lijuan Fu
- Department of Infectious Disease, Xiang’an Hospital of Xiamen University, Xiamen, China
- Xiamen Quality Control Center of Infectious Diseases, Xiamen, China
| | - Ningshao Xia
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China
- National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, Xiamen University, Xiamen, China
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Golkocheva-Markova E, Ismailova C, Kevorkyan A, Raycheva R, Zhelyazkova S, Kotsev S, Pishmisheva M, Rangelova V, Stoyanova A, Yoncheva V, Tenev T, Gladnishka T, Trifonova I, Christova I, Dimitrov R, Bruni R, Ciccaglione AR. Age and Gender Trends in the Prevalence of Markers for Hepatitis E Virus Exposure in the Heterogeneous Bulgarian Population. Life (Basel) 2023; 13:1345. [PMID: 37374127 DOI: 10.3390/life13061345] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 06/02/2023] [Accepted: 06/06/2023] [Indexed: 06/29/2023] Open
Abstract
The prevalence of hepatitis E virus (HEV) in the Bulgarian population remains underestimated. The aim of the present study was to evaluate age and gender trends in HEV prevalence in the heterogeneous Bulgarian population. Stored serum samples from blood donors and different patient sub-populations-kidney recipients (KR), patients with Guillain-Barre syndrome (GBS), Lyme disease (LD), patients with liver involvement and a clinical diagnosis other than viral hepatitis A and E (non-AE), hemodialysis (HD) and HIV-positive patients (HIV)-were retrospectively investigated for markers of past and recent/ongoing HEV infection. The estimated overall seroprevalence of past infection was 10.6%, ranging from 5.9% to 24.5% for the sub-populations evaluated, while the seroprevalence of recent/ongoing HEV infection was 7.5%, ranging from 2.1% to 20.4%. The analysis of the individual sub-populations showed a different prevalence with respect to sex. In regard to age, the cohort effect was preserved, as a multimodal pattern was observed only for the GBS sub-population. Molecular analysis revealed HEV 3f and 3e. The type of the population is one of the main factors on which the anti-HEV prevalence depends, highlighting the need for the development of guidelines related to the detection and diagnosis of HEV infection with regard to specific patient populations.
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Affiliation(s)
- Elitsa Golkocheva-Markova
- NRL Hepatitis Viruses, Department of Virology, National Center of Infectious and Parasitic Diseases, 1504 Sofia, Bulgaria
| | - Chiydem Ismailova
- NRL Hepatitis Viruses, Department of Virology, National Center of Infectious and Parasitic Diseases, 1504 Sofia, Bulgaria
| | - Ani Kevorkyan
- Department of Epidemiology and Disaster Medicine, Faculty of Public Health, Medical University, 4002 Plovdiv, Bulgaria
| | - Ralitsa Raycheva
- Department of Social Medicine and Public Health, Faculty of Public Health, Medical University, 4002 Plovdiv, Bulgaria
| | - Sashka Zhelyazkova
- Clinic of Nervous Diseases, University Hospital "Alexandrovska", Medical University, 1431 Sofia, Bulgaria
| | - Stanislav Kotsev
- Department Infectious Diseases, Regional Hospital, 4400 Pazardzhik, Bulgaria
| | - Maria Pishmisheva
- Department Infectious Diseases, Regional Hospital, 4400 Pazardzhik, Bulgaria
| | - Vanya Rangelova
- Department of Epidemiology and Disaster Medicine, Faculty of Public Health, Medical University, 4002 Plovdiv, Bulgaria
| | - Asya Stoyanova
- NRL Enteroviruses, Department of Virology, National Center of Infectious and Parasitic Diseases, 1504 Sofia, Bulgaria
| | - Viliana Yoncheva
- NRL Hepatitis Viruses, Department of Virology, National Center of Infectious and Parasitic Diseases, 1504 Sofia, Bulgaria
| | - Tencho Tenev
- NRL Hepatitis Viruses, Department of Virology, National Center of Infectious and Parasitic Diseases, 1504 Sofia, Bulgaria
| | - Teodora Gladnishka
- NRL of Vector-Borne Infections, Listeria and Leptospires, Department of Microbiology, National Center of Infectious and Parasitic Diseases, 1504 Sofia, Bulgaria
| | - Iva Trifonova
- NRL of Vector-Borne Infections, Listeria and Leptospires, Department of Microbiology, National Center of Infectious and Parasitic Diseases, 1504 Sofia, Bulgaria
| | - Iva Christova
- NRL of Vector-Borne Infections, Listeria and Leptospires, Department of Microbiology, National Center of Infectious and Parasitic Diseases, 1504 Sofia, Bulgaria
| | - Roumen Dimitrov
- Institute of Mathematics and Informatics, Bulgarian Academy of Sciences, 1000 Sofia, Bulgaria
| | - Roberto Bruni
- Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
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Takakusagi S, Kakizaki S, Takagi H. The Diagnosis, Pathophysiology, and Treatment of Chronic Hepatitis E Virus Infection-A Condition Affecting Immunocompromised Patients. Microorganisms 2023; 11:1303. [PMID: 37317277 DOI: 10.3390/microorganisms11051303] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 05/01/2023] [Accepted: 05/13/2023] [Indexed: 06/16/2023] Open
Abstract
Hepatitis E is a zoonosis caused by hepatitis E virus (HEV), which was first discovered 40 years ago. Twenty million HEV infections worldwide are estimated each year. Most hepatitis E cases are self-limiting acute hepatitis, but the virus has been recognized to cause chronic hepatitis. Following the first case report of chronic hepatitis E (CHE) in a transplant recipient, CHE has recently been identified as associated with chronic liver damage induced by HEV genotypes 3, 4, and 7-usually in immunocompromised patients such as transplant recipients. In addition, patients infected with HIV and those receiving chemotherapy for malignancy, along with patients with rheumatic disease and COVID-19, have recently been reported as having CHE. CHE can be easily misdiagnosed by usual diagnostic methods of antibody response, such as anti-HEV IgM or IgA, because of the low antibody response in the immunosuppressive condition. HEV RNA should be evaluated in these patients, and appropriate treatments-such as ribavirin-should be given to prevent progression to liver cirrhosis or liver failure. While still rare, cases of CHE in immunocompetent patients have been reported, and care must be taken not to overlook these instances. Herein, we conduct an overview of hepatitis E, including recent research developments and management of CHE, in order to improve our understanding of such cases. The early diagnosis and treatment of CHE should be performed to decrease instances of hepatitis-virus-related deaths around the world.
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Affiliation(s)
- Satoshi Takakusagi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22 Fujioka, Fujioka 375-0024, Gunma, Japan
| | - Satoru Kakizaki
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki 370-0829, Gunma, Japan
| | - Hitoshi Takagi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22 Fujioka, Fujioka 375-0024, Gunma, Japan
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Mahsoub HM, Heffron CL, Hassebroek AM, Sooryanarain H, Wang B, LeRoith T, Rodríguez GR, Tian D, Meng XJ. Fetal Loss in Pregnant Rabbits Infected with Genotype 3 Hepatitis E Virus Is Associated with Altered Inflammatory Responses, Enhanced Virus Replication, and Extrahepatic Virus Dissemination with Positive Correlations with Increased Estradiol Level. mBio 2023; 14:e0041823. [PMID: 36939322 PMCID: PMC10128027 DOI: 10.1128/mbio.00418-23] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 02/24/2023] [Indexed: 03/21/2023] Open
Abstract
Hepatitis E virus (HEV) causes adverse clinical outcomes in pregnant women, but the underlying mechanisms remain poorly understood. To delineate the mechanisms of pregnancy-associated adverse effects during HEV infection, we utilized a genotype 3 HEV from rabbit (HEV-3ra) and its cognate host (rabbits) to systematically investigate the clinical consequences, viral replication dynamics, and host immune and hormonal responses of HEV infection during pregnancy. We found a significant fetal loss of 23% in HEV-infected pregnant rabbits, indicating an early-stage miscarriage. HEV infection in pregnant rabbits was characterized by higher viral loads in feces, intestinal contents, liver, and spleen tissues, as well as a longer and earlier onset of viremia than in infected nonpregnant rabbits. HEV infection altered the pattern of cytokine gene expressions in the liver of pregnant rabbits and caused a transient increase of serum interferon gamma (IFN-γ) shortly after a notable increase in viral replication, which may contribute to early fetal loss. Histological lesions in the spleen were more pronounced in infected pregnant rabbits, although moderate liver lesions were seen in both infected pregnant and nonpregnant rabbits. Total bilirubin was elevated in infected pregnant rabbits. The serum levels of estradiol (E2) in HEV-infected pregnant rabbits were significantly higher than those in mock-infected pregnant rabbits at 14 days postinoculation (dpi) and correlated positively with higher viral loads in feces, liver, and spleen tissues at 28 dpi, suggesting that it may play a role in extrahepatic virus dissemination. The results have important implications for understanding the severe diseases associated with HEV infection during pregnancy. IMPORTANCE HEV causes adverse pregnancy outcomes, with a mortality rate of >30% in pregnant women, but the underlying mechanisms are poorly understood. In this study, we utilized HEV-3ra and its cognate host (pregnant rabbit) to delineate the potential underlying mechanisms of pregnancy-associated adverse outcomes during HEV infection. We found that infected pregnant rabbits had a fetal loss of 23%, which coincided with enhanced viral replication and an elevated systemic IFN-γ response, followed by longer viremia duration and extrahepatic viral dissemination. Estradiol levels were increased in infected pregnant rabbits and correlated positively with higher fecal viral shedding and higher viral loads in liver and spleen tissues. Infected pregnant rabbits had more pronounced splenic lesions, higher serum total bilirubin, and an altered cytokine gene expression profile in the liver. The results will contribute to our understanding of the mechanisms of HEV-associated adverse pregnancy outcomes.
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Affiliation(s)
- Hassan M. Mahsoub
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - C. Lynn Heffron
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Anna M. Hassebroek
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Harini Sooryanarain
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Bo Wang
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Tanya LeRoith
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Guillermo Raimundi Rodríguez
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Debin Tian
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Xiang-Jin Meng
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Fralin Life Sciences Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
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Takakusagi S, Takagi H, Yamazaki Y, Kosone T, Nagashima S, Takahashi M, Murata K, Okamoto H. Chronic hepatitis E in an elderly immunocompetent patient who achieved a sustained virologic response with ribavirin treatment. Clin J Gastroenterol 2022; 16:206-215. [PMID: 36403172 DOI: 10.1007/s12328-022-01733-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 11/04/2022] [Indexed: 11/21/2022]
Abstract
A woman in her late 70 s was diagnosed with liver injury at a health examination. Despite treatment with ursodeoxycholic acid at a nearby hospital, her transaminase levels elevated in two peaks. She was transferred to our hospital 77 days after the health examination. She weighed 42 kg and had a low body mass index of 19.8 kg/m2. Viral markers, including immunoglobulin A (IgA) against hepatitis E virus (anti-HEV IgA), were negative. Drug-induced liver injury was negligible. We suspected autoimmune hepatitis because of the patient's female gender and positive antinuclear antibody. However, prednisolone and azathioprine failed to completely improve her hepatitis. On day 643, anti-HEV IgA was re-evaluated and found to be positive. She was diagnosed with autochthonous chronic hepatitis E because the virus strains in the preserved serum on day 77 and the serum on day 643 had identical nucleotide sequences (genotype 3a). Following prednisolone and azathioprine discontinuation, ribavirin (RBV) was administered for 3 months. HEV RNA disappeared and remained negative for more than 6 months after the cessation of RBV. The HEV RNA titer of 6.2 log10 copies/mL on day 77 was unusually high 2.5 months after the onset, suggesting that hepatitis E had already been chronic before immunosuppressive treatment for possible autoimmune hepatitis. After getting married at 23 years old, she had been a housewife and had no comorbidities that might deteriorate her immunity. Chronicity should be kept in mind when encountering HEV infection in elderly and underweight patients.
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Affiliation(s)
- Satoshi Takakusagi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22 Fujioka, Fujioka, Gunma, 375-0024, Japan
| | - Hitoshi Takagi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22 Fujioka, Fujioka, Gunma, 375-0024, Japan.
| | - Yuichi Yamazaki
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, 3-39-15 Showa-Machi, Maebashi, Gunma, 371-8511, Japan
| | - Takashi Kosone
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22 Fujioka, Fujioka, Gunma, 375-0024, Japan
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Kazumoto Murata
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
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7
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Bahoussi AN, Guo YY, Wang PH, Dahdouh A, Wu C, Xing L. Genomic characteristics and recombination patterns of swine hepatitis E virus in China. Transbound Emerg Dis 2022; 69:e3273-e3281. [PMID: 35511197 DOI: 10.1111/tbed.14585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 04/30/2022] [Accepted: 05/02/2022] [Indexed: 11/28/2022]
Abstract
Zoonotic hepatitis E, mainly caused by swine hepatitis E virus (sHEV), is endemic in China, causing great economic disruption and public health threats. Although recombination is critical for the evolution of viruses, there is a limited assessment of its occurrence among sHEVs. Herein, we analyzed all available sHEV full-length genomes isolated in China during the past two decades (40 isolates) compared to 72 other sHEV strains isolated in different countries and determined that sHEV genotype 4 (sHEV4) dominates China. Eight potential natural recombination events were identified, four of which occurred in China and were mainly between sHEV4 strains, indicating the distinct character of China sHEV. One intergenotype recombination event was found in China, alarming the emergence of a new sHEV lineage that could become a critical threat to human health. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Amina Nawal Bahoussi
- Institutes of Biomedical Sciences, Shanxi University, 92 Wucheng Road, Taiyuan, Shanxi Province, 030006, China
| | - Yan-Yan Guo
- Institutes of Biomedical Sciences, Shanxi University, 92 Wucheng Road, Taiyuan, Shanxi Province, 030006, China
| | - Pei-Hua Wang
- Institutes of Biomedical Sciences, Shanxi University, 92 Wucheng Road, Taiyuan, Shanxi Province, 030006, China
| | - Amina Dahdouh
- Institutes of Biomedical Sciences, Shanxi University, 92 Wucheng Road, Taiyuan, Shanxi Province, 030006, China
| | - Changxin Wu
- Institutes of Biomedical Sciences, Shanxi University, 92 Wucheng Road, Taiyuan, Shanxi Province, 030006, China.,Shanxi Provincial Key Laboratory of Medical Molecular Cell Biology, Shanxi University, 92 Wucheng Road, Taiyuan, 030006, China.,Shanxi Provincial Key Laboratory for Prevention and Treatment of Major Infectious Diseases, 92 Wucheng Road, Taiyuan, 030006, China
| | - Li Xing
- Institutes of Biomedical Sciences, Shanxi University, 92 Wucheng Road, Taiyuan, Shanxi Province, 030006, China.,Shanxi Provincial Key Laboratory of Medical Molecular Cell Biology, Shanxi University, 92 Wucheng Road, Taiyuan, 030006, China.,Shanxi Provincial Key Laboratory for Prevention and Treatment of Major Infectious Diseases, 92 Wucheng Road, Taiyuan, 030006, China
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8
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Zhou Z, Xie Y, Wu C, Nan Y. The Hepatitis E Virus Open Reading Frame 2 Protein: Beyond Viral Capsid. Front Microbiol 2021; 12:739124. [PMID: 34690982 PMCID: PMC8529240 DOI: 10.3389/fmicb.2021.739124] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Accepted: 09/20/2021] [Indexed: 12/20/2022] Open
Abstract
Hepatitis E virus (HEV) is a zoonotic pathogen causing hepatitis in both human and animal hosts, which is responsible for acute hepatitis E outbreaks worldwide. The 7.2 kb genome of the HEV encodes three well-defined open reading frames (ORFs), where the ORF2 translation product acts as the major virion component to form the viral capsid. In recent years, besides forming the capsid, more functions have been revealed for the HEV-ORF2 protein, and it appears that HEV-ORF2 plays multiple functions in both viral replication and pathogenesis. In this review, we systematically summarize the recent research advances regarding the function of the HEV-ORF2 protein such as application in the development of a vaccine, regulation of the innate immune response and cellular signaling, involvement in host tropism and participation in HEV pathogenesis as a novel secretory factor. Progress in understanding more of the function of HEV-ORF2 protein beyond the capsid protein would contribute to improved control and treatment of HEV infection.
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Affiliation(s)
- Zhaobin Zhou
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Yangling, China
| | - Yinqian Xie
- Shaanxi Animal Disease Prevention and Control Center, Xi’an, China
| | - Chunyan Wu
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Yangling, China
| | - Yuchen Nan
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Yangling, China
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9
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Gorris M, van der Lecq BM, van Erpecum KJ, de Bruijne J. Treatment for chronic hepatitis E virus infection: A systematic review and meta-analysis. J Viral Hepat 2021; 28:454-463. [PMID: 33301609 PMCID: PMC7898834 DOI: 10.1111/jvh.13456] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 11/09/2020] [Accepted: 11/23/2020] [Indexed: 12/19/2022]
Abstract
Hepatitis E virus infection can cause chronic hepatitis in immunocompromised patients with significant chance of progressive fibrosis and possibly cirrhosis. The aim of this systematic review was to summarize the efficacy and safety of the various treatment options for chronic hepatitis E. We performed a systematic literature search. The primary outcome measure was a sustained virological response (SVR). Secondary end points were rapid virological response (RVR), relapse rates, side effects and adverse events. Forty-four articles were included with a total of 582 patients. Reduction of immunosuppressive medication induced viral clearance in 55/174 (32%) of the patients. Meta-analysis of 395 patients showed a pooled SVR rate of 78% (95-CI 72%-84%) after ribavirin treatment. Twenty-five per cent of the patients obtained a RVR, whereas a relapse occurred in 18% of the patients. Anaemia during treatment led to dose reduction, use of erythropoietin and/or blood transfusion in 37% of the patients. A second treatment attempt with ribavirin led to a SVR in 39/51 (76%) of the patients. Pegylated interferon-alpha was administered to 13 patients and SVR was obtained in 85%. Two patients (15%) suffered from acute transplant rejection during treatment with interferon. In conclusion, reduction of immunosuppressive medication and treatment with ribavirin is safe, generally well tolerated and induced viral clearance in 32% and 78% of patients, respectively. Therefore, ribavirin should be considered as first treatment step for chronic hepatitis E. Treatment with pegylated interferon-alpha increases the risk of transplant rejection and should therefore be administered with great caution.
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Affiliation(s)
- Myrte Gorris
- Department of Gastroenterology & HepatologyUniversity Medical Center UtrechtUtrechtThe Netherlands
| | - Bernice M. van der Lecq
- Department of Gastroenterology & HepatologyUniversity Medical Center UtrechtUtrechtThe Netherlands
| | - Karel J. van Erpecum
- Department of Gastroenterology & HepatologyUniversity Medical Center UtrechtUtrechtThe Netherlands
| | - Joep de Bruijne
- Department of Gastroenterology & HepatologyUniversity Medical Center UtrechtUtrechtThe Netherlands
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10
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Remondegui C, Ceballos S, Arce LP, Pintado E, Vidaurre R, Nitschko H, Osterman A, Vizoso Pinto MG. Serologic evidence of the circulation of the hepatitis E virus and the prevalence of antibodies against hepatitis A in an indigenous population in northern Argentina. Rev Argent Microbiol 2021; 53:314-324. [PMID: 33648797 DOI: 10.1016/j.ram.2020.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 08/31/2020] [Accepted: 10/02/2020] [Indexed: 11/29/2022] Open
Abstract
In 2005 a universal vaccination program against hepatitis A was introduced in Argentina. Nevertheless, there are still some unvaccinated marginal population groups. There are no data about the seroprevalence of hepatitis E in the northern region of Argentina mainly because of lack of awareness of this emergent pathogen. We aimed to determine the seroprevalence of hepatitis A, and hepatitis E in an indigenous population in northern Argentina. One hundred and twenty six (126) donor serum samples collected near San Salvador de Jujuy were analyzed for anti-HAV IgG and HEV IgG and IgM, alkaline phosphatase and transaminase values. Volunteers were interviewed about their living conditions, animal farming, consumption of tap water or river water, and level of education. Seroprevalence of specific anti-HAV antibodies was high (80.2%, 95% confidence interval, 72.1-86.7%) in children under 5 years of age, indicating early infection in life. Seroprevalence of anti-HEV antibodies was 5.6% (95% CI: 2.3-11.2%), being slightly higher than the values found in healthy patients from other regions of the country. Although we could not characterize the genotype of the circulating HEV strain, the clear epidemiological difference between seroprevalence of HAV and HEV in a community with poor sanitary conditions suggest that the circulating HEV strains spread through a different transmission route than HAV. Furthermore a significant correlation between anti-HEV IgG and swine farming was found (p<0.05), which supports a zoonotic transmission path. We reassessed the epidemiological pattern of HAV infection and reported evidence of HEV infection for the first-time in a community belonging to the Guarani ethnic group, highlighting the need to include hepatitis E testing in routine diagnostics in the region.
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Affiliation(s)
| | | | - Lorena Paola Arce
- Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET-UNT, San Miguel de Tucumán, Argentina; Laboratorio de Ciencias Básicas, OR. Genética, Facultad de Medicina, INSIBIO (CONICET-UNT), Universidad Nacional de Tucumán, Argentina
| | | | - Rene Vidaurre
- Hospital Paterson de San Pedro de Jujuy, Jujuy, Argentina
| | - Hans Nitschko
- Max von Pettenkofer Institute, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU München, Munich, Germany; German Center for Infection Research (DZIF), Partner Site Munich, Germany
| | - Andreas Osterman
- Max von Pettenkofer Institute, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU München, Munich, Germany; German Center for Infection Research (DZIF), Partner Site Munich, Germany
| | - María Guadalupe Vizoso Pinto
- Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET-UNT, San Miguel de Tucumán, Argentina; Laboratorio de Ciencias Básicas, OR. Genética, Facultad de Medicina, INSIBIO (CONICET-UNT), Universidad Nacional de Tucumán, Argentina.
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11
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Ankcorn M, Said B, Morgan D, Elsharkawy AM, Maggs J, Ryder S, Valliani T, Gordon F, Abeysekera K, Suri D, McPherson S, Galliford J, Smith B, Pelosi E, Bansal S, Bethune C, Sheridan D, Vine L, Tedder RS, Ijaz S, Zuckerman M, Dalton H, Healy B, Donati M, Bicknell K, Evans C, Poller B, Smit E, Halsema C, Williams E, Raza M, McGann H, Irving W, Douthwaite S, Ch'ng CL, McCaughey C, Irish D. Persistent Hepatitis E virus infection across England and Wales 2009-2017: Demography, virology and outcomes. J Viral Hepat 2021; 28:420-430. [PMID: 33073452 DOI: 10.1111/jvh.13424] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 09/20/2020] [Accepted: 10/02/2020] [Indexed: 01/11/2023]
Abstract
The first clinical case of persistent HEV infection in England was reported in 2009. We describe the demography, virology and outcomes of patients identified with persistent HEV infection in England and Wales between 2009 and 2017. A series of 94 patients with persistent HEV infection, defined by HEV viraemia of more than 12 weeks, was identified through routine reference laboratory testing. Virology, serology and clinical data were recorded through an approved PHE Enhanced Surveillance System. Sixty-six cases (70.2%) were transplant recipients, 16 (17.0%) had an underlying haematological malignancy without stem cell transplantation, six (6.4%) had advanced HIV infection, five (5.3%) were otherwise immunosuppressed, and one patient (1.1%) had no identified immunosuppression. Retrospective analysis of 46 patients demonstrated a median 38 weeks of viraemia before diagnostic HEV testing. At initial diagnosis, 16 patients (17.0%) had no detectable anti-HEV serological response. Of 65 patients treated with ribavirin monotherapy, 11 (16.9%) suffered virological relapse despite undetectable RNA in plasma or stool at treatment cessation. Persistent HEV infection remains a rare diagnosis, but we demonstrate that a broad range of immunocompromised patients are susceptible. Both lack of awareness and the pauci-symptomatic nature of persistent HEV infection likely contribute to significant delays in diagnosis. Diagnosis should rely on molecular testing since anti-HEV serology is insufficient to exclude persistent HEV infection. Finally, despite treatment with ribavirin, relapses occur even after cessation of detectable faecal shedding of HEV RNA, further emphasising the requirement to demonstrate sustained virological responses to treatment.
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Affiliation(s)
- Michael Ankcorn
- Blood Borne Virus Unit, Virus Reference Department, National Infection Service, Public Health England, London, UK.,Transfusion Microbiology, National Health Service Blood and Transplant, London, UK
| | - Bengü Said
- Emerging Infections and Zoonoses, National Infection Service, Public Health England, London, UK
| | - Dilys Morgan
- Emerging Infections and Zoonoses, National Infection Service, Public Health England, London, UK
| | | | - James Maggs
- Department of Gastroenterology, Buckinghamshire Healthcare NHS Trust, Buckinghamshire, UK
| | - Stephen Ryder
- Department of Hepatology, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Talal Valliani
- North Bristol Liver Unit, North Bristol NHS Trust, Southmead Hospital, Bristol, UK
| | - Fiona Gordon
- Department of Hepatology, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | - Kushala Abeysekera
- Department of Hepatology, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | - Deepak Suri
- Department of Hepatology, University College London Hospitals, London, UK
| | - Stuart McPherson
- Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, & Institute of Cellular Medicine, Newcastle University, Newcastle, UK
| | - Jack Galliford
- Department of Nephrology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Belinda Smith
- Department of Hepatology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Emanuela Pelosi
- Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Sanjay Bansal
- Department of Paediatric Hepatology, Gastroenterology & Nutrition Center, King's College Hospital NHS Foundation Trust, London, UK
| | - Claire Bethune
- Department of Immunology and Allergy, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - David Sheridan
- South West Liver Unit, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Louisa Vine
- South West Liver Unit, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Richard S Tedder
- Blood Borne Virus Unit, Virus Reference Department, National Infection Service, Public Health England, London, UK.,Transfusion Microbiology, National Health Service Blood and Transplant, London, UK.,Department of Medicine, Imperial College London, London, UK
| | - Samreen Ijaz
- Blood Borne Virus Unit, Virus Reference Department, National Infection Service, Public Health England, London, UK
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12
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Lin XN, Lin QX, Li SM, Xie KP, Hou J, Chen R. Hepatitis E virus re-infection accelerates hepatocellular carcinoma development and relapse in a patient with liver cirrhosis: A case report and review of literature. World J Hepatol 2020; 12:1358-1366. [PMID: 33442461 PMCID: PMC7772737 DOI: 10.4254/wjh.v12.i12.1358] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 10/04/2020] [Accepted: 10/20/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) superinfection is a suspected promoting factor for hepatocellular carcinoma (HCC) in patients with chronic hepatitis and cirrhosis. However, to date, very few cases of HEV-related HCC have been reported. Nevertheless, the role of HEV re-infection in cirrhotic liver without other chronic hepatitis infections has rarely been explored. CASE SUMMARY A 53-year-old male farmer was diagnosed with liver cirrhosis and splenomegaly in August 2016, accompanied with negative HEV-IgM and positive HEV-IgG. No evidence of hepatitis B virus or hepatitis C virus infection was found. Since then the patient was evaluated for liver function and viral parameters every 3 mo. In June 2017, the patient presented severe fatigue with whole body itching and was diagnosed with HCC. Afterwards this patient experienced quick HCC development, progression, relapse, and metastasis in the following 8 mo, and presented persistent dual positivity of HEV-IgM and HEV-IgG. This patient had a long history of smoking and alcohol consumption. CONCLUSION This unique case invokes the importance of HEV surveillance and treatment among cirrhotic patients, HCC cases, and blood donors.
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Affiliation(s)
- Xiao-Na Lin
- The Laboratory of Computational Medicine and Systems Biology, School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong Province, China
| | - Qiu-Xiong Lin
- Department of Infectious Disease, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Shu-Mei Li
- Department of Infectious Disease, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Ke-Ping Xie
- School of Medicine, South China University of Technology, Guangzhou 510000, Guangdong Province, China
| | - Jun Hou
- The Laboratory of Computational Medicine and Systems Biology, School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong Province, China
| | - Ren Chen
- Department of Infectious Disease, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China.
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13
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Mirazo S, Arbiza J. Hepatitis E and chronic liver damage in apparently immunocompetent individuals: Now what? Ann Hepatol 2020; 18:539-540. [PMID: 31130468 DOI: 10.1016/j.aohep.2019.05.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Accepted: 05/02/2019] [Indexed: 02/04/2023]
Abstract
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide, accounting for 20 million infections per year and 70,000 deaths. In developed regions, sporadic locally acquired infections are most commonly caused by HEV3, and in this setting Hepatitis E is mainly asymptomatic. However, certain group of patients HEV infection may present as a fulminant disease or progressive fibrosis. Chronic HEV infection can occur in immunocompromised individuals, including transplant recipients. A high proportion of solid-organ transplant recipients exposed to HEV are at risk of developing a chronic infection, frequently associated to extrahepatic manifestations. However, clinical phenotype of sporadic cases of HEV infection is still poorly characterized. A recent work, focused on the retrospective study of HEV as a causative agent of viral hepatitis in adults form Mexico, pose novel challenges to understanding the HEV threat to human health. Main findings are brought into discussion herein, in light of the current knowledge concerning viral pathogenesis and host-pathogen interaction. The role of HEV infection in the development of chronic liver disease is also discussed. Hepatitis E is a cause of mortality and morbidity which negatively impacts the prognosis of patients with chronic liver disease. Recognition of HEV infection must be improved, by increasing awareness and knowledge of the clinical phenotype of the disease.
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Affiliation(s)
- Santiago Mirazo
- Sección Virología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
| | - Juan Arbiza
- Sección Virología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
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14
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Viera-Segura O, Realpe-Quintero M, Panduro A, Roman S, Jose-Abrego A, Gonzalez-Aldaco K, Trujillo-Ochoa JL, Fierro NA. First detection of hepatitis E virus genotype 3 as a common infectious agent in patients with chronic liver damage in Mexico. Ann Hepatol 2020; 18:571-577. [PMID: 31080055 DOI: 10.1016/j.aohep.2019.03.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 03/08/2019] [Accepted: 03/26/2019] [Indexed: 02/07/2023]
Abstract
INTRODUCTION AND OBJECTIVES To characterize the virological features of hepatitis E virus (HEV) in serum from patients exhibiting chronic liver damage. METHODS A data-base of 513 unrelated individuals from West-Mexico with liver-disease determined by clinical and biochemical tests and transient elastography between 2011 and 2016 were retrospectively analyzed. According to infectious etiologies, patients were classified as hepatitis B virus (HBV)-, hepatitis C virus (HCV)-infected patients, and patients exhibiting chronic liver damage with non-identified infectious etiological agent (NIIEA). Available serum samples from NIIEA-patients were tested by RT-nPCR for the presence of HEV-RNA and partially sequenced for genotyping. RESULTS Out of the 513 cases, 5.85% were patients infected with HBV, 67.64% with HCV, and 26.51% were NIIEA-patients. Among 76 available samples from NIIEA-cases, 30.26% tested positive for HEV-RNA. Twelve (15.79%) partial HEV sequences allowed phylogenetic analysis, revealing the classification of HEV as HEV-Gt3. Advanced fibrosis (F3-F4 stage) was found in a 26.1% of patients with HEV-active infection. CONCLUSION Although HCV is the main infectious agent related to chronic liver disease in Mexico, liver damage without an infectious etiology is common. Our findings reveal that an elevated rate of chronic liver disease might be represented by autochthonous infection of HEV-Gt3, whose detection makes Mexico unique in Latin-America with the circulation of HEV strains belonging to three genotypes (Gt1, Gt2, and Gt3). Thus, HEV infection should be a matter of health concern, and mandates for HEV screening to properly handle this commonly undiagnosed disease.
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Affiliation(s)
- Oliver Viera-Segura
- Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico; Immunovirology Unit, Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, "Fray Antonio Alcalde", Department of Physiology, Health Sciences Center, University of Guadalajara, Guadalajara, 44280 Jalisco, Mexico
| | - Mauricio Realpe-Quintero
- Department of Veterinarian Medicine, Biological-Agricultural Sciences, University of Guadalajara, Nextipac, Zapopan, 44600 Jalisco, Mexico
| | - Arturo Panduro
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara "Fray Antonio Alcalde", and Health Sciences Center, University of Guadalajara, Hospital #278, Col. El Retiro, Guadalajara, 44280 Jalisco, Mexico
| | - Sonia Roman
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara "Fray Antonio Alcalde", and Health Sciences Center, University of Guadalajara, Hospital #278, Col. El Retiro, Guadalajara, 44280 Jalisco, Mexico
| | - Alexis Jose-Abrego
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara "Fray Antonio Alcalde", and Health Sciences Center, University of Guadalajara, Hospital #278, Col. El Retiro, Guadalajara, 44280 Jalisco, Mexico
| | - Karina Gonzalez-Aldaco
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara "Fray Antonio Alcalde", and Health Sciences Center, University of Guadalajara, Hospital #278, Col. El Retiro, Guadalajara, 44280 Jalisco, Mexico
| | - Jorge L Trujillo-Ochoa
- Immunovirology Unit, Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, "Fray Antonio Alcalde", Department of Physiology, Health Sciences Center, University of Guadalajara, Guadalajara, 44280 Jalisco, Mexico
| | - Nora A Fierro
- Immunovirology Unit, Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, "Fray Antonio Alcalde", Department of Physiology, Health Sciences Center, University of Guadalajara, Guadalajara, 44280 Jalisco, Mexico.
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15
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Abstract
While the majority of worldwide hepatitis E viral (HEV) infections that occur in people are from contaminated water or food sources, there has also been a steadily rising number of reported cases of transfusion-transmitted HEV (TT-HEV) in blood donation recipients. For most, HEV infection is acute, self-limiting and asymptomatic. However, patients that are immunocompromised, especially transplant patients, are at much higher risk for developing chronic infections, which can progress to cirrhosis and liver failure, along with overall increased mortality. Because of the rising trend of HEV serological prevalence among the global population, and the fact that TT-HEV infection can cause serious clinical consequences among those patients most at need for blood donation, the need for screening for TT-HEV has been gaining in prominence as an important public health concern for both developing and developed countries. In the review, we summarise evidence for and notable cases of TT-HEV infections, the various aspects of HEV screening protocols and recent trends in the implementation of TT-HEV broad-based blood screening programmes.
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16
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Wang Y, Liu S, Pan Q, Zhao J. Chronic hepatitis E in an immunocompetent patient. Clin Res Hepatol Gastroenterol 2020; 44:e66-e68. [PMID: 31477532 DOI: 10.1016/j.clinre.2019.08.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 08/06/2019] [Indexed: 02/04/2023]
Affiliation(s)
- Yijin Wang
- Department of Pathology and Hepatology, the 5th Medical Center, Chinese PLA General Hospital, China
| | - Shuhong Liu
- Department of Pathology and Hepatology, the 5th Medical Center, Chinese PLA General Hospital, China
| | - Qiuwei Pan
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, room Na-617, 's-Gravendijkwal 230, NL-3015 CE Rotterdam, The Netherlands.
| | - Jingmin Zhao
- Department of Pathology and Hepatology, the 5th Medical Center, Chinese PLA General Hospital, China.
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17
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Colson P, Schleinitz N, Vely F, Poveda JD, Jacomo V, Demerle C, Borentain P, Gerolami R. Chronic hepatitis E in absence of severe immune deficiency. Clin Res Hepatol Gastroenterol 2020; 44:e1-e4. [PMID: 31327621 DOI: 10.1016/j.clinre.2019.06.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Revised: 06/01/2019] [Accepted: 06/04/2019] [Indexed: 02/04/2023]
Affiliation(s)
- Philippe Colson
- Aix-Marseille University, Institut de Recherche pour le Développement (IRD), Assistance Publique - Hôpitaux de Marseille (AP-HM), MEPHI, 27, boulevard Jean Moulin, Marseille 13005, France; IHU Méditerranée Infection, 19-21, boulevard Jean Moulin, Marseille 13005, France.
| | - Nicolas Schleinitz
- Assistance Publique - Hôpitaux de Marseille (AP-HM), Centre Hospitalo-Universitaire Timone, Service de Médecine Interne, 264 rue Saint-Pierre, Marseille cedex 05 13385, France
| | - Frédéric Vely
- Aix Marseille University, CNRS, Inserm, CIML, Marseille, France; AP-HM, Hôpital de la Timone, Service d'Immunologie, Marseille-Immunopôle, 27, boulevard Jean-Moulin, Marseille 13005, France; Assistance Publique - Hôpitaux de Marseille (AP-HM), Centre Hospitalo-Universitaire Timone, Centre d'Immunologie, département Déficits immunitaires, 264, rue Saint-Pierre, Marseille cedex 05 13385, France
| | - Jean-Dominique Poveda
- Cerba Laboratories, Cerba HealthCare, 7/11, rue de l'Equerre, Saint-Ouen-l'Aumône 95310, France
| | - Véronique Jacomo
- Laboratoire Eurofins Biomnis, 17/19, avenue Tony Garnier, Lyon 69007, France
| | - Clémence Demerle
- Assistance Publique - Hôpitaux de Marseille (AP-HM), Centre Hospitalo-Universitaire Timone, Centre d'Immunologie, département Déficits immunitaires, 264, rue Saint-Pierre, Marseille cedex 05 13385, France
| | - Patrick Borentain
- Assistance Publique - Hôpitaux de Marseille (AP-HM), Centre Hospitalo-Universitaire Timone, Service d'Hépato-Gastro-Enterologie, 264, rue Saint-Pierre, Marseille cedex 05 13385, France
| | - René Gerolami
- Assistance Publique - Hôpitaux de Marseille (AP-HM), Centre Hospitalo-Universitaire Timone, Service d'Hépato-Gastro-Enterologie, 264, rue Saint-Pierre, Marseille cedex 05 13385, France
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18
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Chauhan A, Webb G, Ferguson J. Clinical presentations of Hepatitis E: A clinical review with representative case histories. Clin Res Hepatol Gastroenterol 2019; 43:649-657. [PMID: 30808575 PMCID: PMC6864596 DOI: 10.1016/j.clinre.2019.01.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Revised: 01/03/2019] [Accepted: 01/21/2019] [Indexed: 02/04/2023]
Abstract
Hepatitis E virus (HEV) typically causes an acute, self-limiting hepatitis and is among the commonest cause of such presentations. Hepatitis E viral infection is also increasingly recognized as a cause of chronic hepatitis amongst the immunocompromised, particularly amongst solid organ transplant recipients. Chronic HEV infection remains an underdiagnosed disease and chronic infection can lead to rapidly progressive liver fibrosis and cirrhosis. This review examines current understanding of the HEV. We illustrate typical clinical presentations, management strategies [(based upon guidelines from both the British Transplant Society (BTS) and European Association for the study of liver (EASL)] and outcomes of HEV infection in different cohorts of patients by highlighting select transplant and non-transplant patient cases, from one of the largest tertiary Hepatology centres in Europe.
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Affiliation(s)
- Abhishek Chauhan
- NIHR Birmingham Biomedical Research Centre, United Kingdom; Liver unit, University Hospitals Birmingham, United Kingdom; Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom.
| | - Gwilym Webb
- Liver unit, University Hospitals Birmingham, United Kingdom; Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom
| | - James Ferguson
- Liver unit, University Hospitals Birmingham, United Kingdom
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Beer A, Holzmann H, Pischke S, Behrendt P, Wrba F, Schlue J, Drebber U, Neudert B, Halilbasic E, Kreipe H, Lohse A, Sterneck M, Wedemeyer H, Manns M, Dienes HP. Chronic Hepatitis E is associated with cholangitis. Liver Int 2019; 39:1876-1883. [PMID: 31102493 PMCID: PMC6790616 DOI: 10.1111/liv.14137] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Revised: 12/21/2018] [Accepted: 02/06/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIMS Sporadic hepatitis E is an emerging indigenous disease in Europe induced by genotype 3 of the virus. While the disease takes an acute self-limited course in immunocompetent individuals, under immunocompromised conditions chronic hepatitis E might develop. The histology of chronic hepatitis E has not been described in detail systematically. METHODS Liver biopsies from 19 immunosuppressed patients with chronic hepatitis E were collected: 17 were organ transplant recipients, one had a CD4-deficiency and one had received steroid therapy because of ulcerative colitis. Biopsies were processed with standard stains. Evaluation of histologic activity and fibrosis was performed according to Ishak. Additionally, immunohistochemistry with antibodies directed against open reading frame 2 and 3 of the virus was performed and liver biopsies were tested for hepatitis E virus RNA. RESULTS Biochemical data showed an increase in alanine transaminase, aspartate transaminase, gamma-glutamyl transferase and total bilirubin. Histopathology displayed typical features of chronic hepatitis with mild to moderate activity. The number of polymorphonuclear leucocytes was considerably increased and all patients had a florid cholangitis that presented as a destructive form in five of them. Hepatocytes and bile duct epithelia stained positive for hepatitis E virus by immunohistochemistry. CONCLUSIONS Chronic hepatitis E in immunocompromised individuals runs a similar course as hepatitis B and C and shows similar histopathology. However, the presence of destructive cholangitis in some cases accompanied by an increased number of polymorphonuclear leucocytes is markedly different. Immunohistochemically the virus is present in bile duct epithelia, seemingly the cause for cholangitis.
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Affiliation(s)
- Andrea Beer
- Department of PathologyMedical University of ViennaViennaAustria
| | | | | | - Patrick Behrendt
- Department of Gastroenterology, Hepatology and EndocrinologyMedical School of HanoverHanoverGermany
| | - Fritz Wrba
- Department of PathologyMedical University of ViennaViennaAustria
| | - Jerome Schlue
- Institute for PathologyMedical School of HanoverHanoverGermany
| | - Uta Drebber
- Institute of PathologyUniversity Hospital CologneCologneGermany
| | - Barbara Neudert
- Department of PathologyMedical University of ViennaViennaAustria
| | - Emina Halilbasic
- Department of GastroenterologyMedical University of ViennaViennaAustria
| | - Hans Kreipe
- Institute for PathologyMedical School of HanoverHanoverGermany
| | | | | | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and EndocrinologyMedical School of HanoverHanoverGermany
| | - Michael Manns
- Department of Gastroenterology, Hepatology and EndocrinologyMedical School of HanoverHanoverGermany
| | - Hans P. Dienes
- Department of PathologyMedical University of ViennaViennaAustria
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20
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Denner J, Pischke S, Steinmann E, Blümel J, Glebe D. Why all blood donations should be tested for hepatitis E virus (HEV). BMC Infect Dis 2019; 19:541. [PMID: 31221098 PMCID: PMC6585104 DOI: 10.1186/s12879-019-4190-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 06/13/2019] [Indexed: 02/06/2023] Open
Abstract
Background Hepatitis E is a liver disease caused by a small RNA virus known as hepatitis E virus (HEV). Four major genotypes infect humans, of which genotype 1 and 2 (HEV-1, HEV-2) are endemic mainly in Asia and responsible for waterborne epidemics. HEV-3 and HEV-4 are widely distributed in pigs and can be transmitted to humans mainly by undercooked meat, and contact with pigs. HEV-3 is the main genotype in industrialised countries with moderate climate conditions and object of this debate. Main text Whereas an HEV-3 infection in healthy humans is mostly asymptomatic, HEV-3 can induce chronic infection in immunocompromised individuals and acute-on-chronic liver failure (ACLF) in patients with underlying liver diseases. The number of reported cases of HEV-infections in industrialised nations increased significantly in the last years. Since HEV-3 has been transmitted by blood transfusion to other humans, testing of blood donors has been introduced or introduction is being discussed in some industrialised countries. In this article we summarise the arguments in favour of testing all blood donations for HEV-3. Conclusion The number of HEV infection in the population and the possibility of HEV transmission by blood transfusion are increasing. Transmission by blood transfusion can be dangerous for the recipients considering their immunosuppressive status, underlying disease or other circumstances requiring blood transfusion. This argues in favour of testing all blood donations for HEV-3 to prevent transmission.
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Affiliation(s)
- Joachim Denner
- Robert Koch Institute, Nordufer 20, 13353, Berlin, Germany.
| | - Sven Pischke
- 1. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany
| | - Eike Steinmann
- Ruhr-Universität Bochum, Universitätsstraße 150, 44801, Bochum, Germany
| | - Johannes Blümel
- Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Germany
| | - Dieter Glebe
- Institute of Medical Virology, National Reference Centre for Hepatitis B and D Viruses, German Center for Infection Research (DZIF), Schubertstr. 81, Justus-Liebig-Universität Giessen, 35392, Giessen, Germany
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21
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Boland F, Martinez A, Pomeroy L, O'Flaherty N. Blood Donor Screening for Hepatitis E Virus in the European Union. Transfus Med Hemother 2019; 46:95-103. [PMID: 31191195 PMCID: PMC6514502 DOI: 10.1159/000499121] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 02/25/2019] [Indexed: 12/11/2022] Open
Abstract
This review article summarises hepatitis E virus (HEV) blood donation screening strategies in effect in the European Union (EU). Since 2012, eight EU countries have implemented HEV screening. Local rates of seroprevalence, RNA incidence, and molecular epidemiology are variable and not usually directly comparable. We report a range of HEV-RNA reactivity rates from 1 in 744 donations (France) to 1 in 8,636 donations (Wales) with an overall EU rate of 1 in 3,109 donations (3.2 million donations screened). HEV genotypes 3c, 3e, and 3f are the most frequently reported subtypes. In these 8 countries, both universal (n = 5) and selective (n = 3) screening policies have been introduced utilising either individual donation (ID; n = 1) or mini-pool (MP; n = 7; MP-6, -16, -24, and -96) testing. We also describe the Irish experience of HEV screening utilising an ID-NAT-based donor screening algorithm which intercepts donations even from those with low-level viraemia; 21 of 56 donors (37.5%) had a viral load (VL) < 100 IU/mL. We performed a MP-24 experiment which may prove useful to colleagues in relation to donor screening and associated blood component transmissibility. Irish results indicate that 59% of donors with a HEV-VL < 450 IU/mL may have screened negative in a MP-24.
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Affiliation(s)
- Fiona Boland
- Irish Blood Transfusion Service (IBTS), NAT Laboratory, Dublin, Ireland
| | | | - Louise Pomeroy
- Irish Blood Transfusion Service (IBTS), NAT Laboratory, Dublin, Ireland
| | - Niamh O'Flaherty
- Irish Blood Transfusion Service (IBTS), NAT Laboratory, Dublin, Ireland
- National Virus Reference Laboratory, University College Dublin (UCD), Dublin, Ireland
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22
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Hofmeister MG, Foster MA, Teshale EH. Epidemiology and Transmission of Hepatitis A Virus and Hepatitis E Virus Infections in the United States. Cold Spring Harb Perspect Med 2019; 9:a033431. [PMID: 29712684 PMCID: PMC6444696 DOI: 10.1101/cshperspect.a033431] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
There are many similarities in the epidemiology and transmission of hepatitis A virus (HAV) and hepatitis E virus (HEV) genotype (gt)3 infections in the United States. Both viruses are enterically transmitted, although specific routes of transmission are more clearly established for HAV than for HEV: HAV is restricted to humans and primarily spread through the fecal-oral route, while HEV is zoonotic with poorly understood modes of transmission in the United States. New cases of HAV infection have decreased dramatically in the United States since infant vaccination was recommended in 1996. In recent years, however, outbreaks have occurred among an increasingly susceptible adult population. Although HEV is the most common cause of acute viral hepatitis in developing countries, it is rarely diagnosed in the United States.
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Affiliation(s)
- Megan G Hofmeister
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia 30329
- Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, Georgia 30329
| | - Monique A Foster
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia 30329
| | - Eyasu H Teshale
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia 30329
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23
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Transmission of a Novel Genotype of Hepatitis E Virus from Bactrian Camels to Cynomolgus Macaques. J Virol 2019; 93:JVI.02014-18. [PMID: 30700602 DOI: 10.1128/jvi.02014-18] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Accepted: 01/18/2019] [Indexed: 12/15/2022] Open
Abstract
Hepatitis E virus (HEV) is zoonotic and a major cause of acute viral hepatitis worldwide. Recently, we identified a novel HEV genotype 8 (HEV8) in Bactrian camels in Xinjiang, China. However, the epidemiology, pathogenicity, and zoonotic potential of HEV8 are unclear. Here, we present the prevalence of HEV8 in China and investigate its pathogenicity and cross-species transmission in cynomolgus macaques. Fresh fecal and milk samples from Bactrian camels collected from four provinces/regions in China were screened for HEV RNA by reverse transcriptase PCR (RT-PCR). An HEV8-positive sample was used to inoculate two cynomolgus macaques to examine the potential for cross-species infection. The pathogenicity of HEV8 was analyzed by testing HEV markers and liver function during the study period and histopathology of liver biopsy specimens at 3, 13, and 25 weeks postinoculation. Extrahepatic replication was tested by using reverse transcriptase quantitative PCR (RT-qPCR) and immunofluorescence assays. The overall prevalence of HEV8 RNA in Chinese Bactrian camels was 1.4% (4/295), and positive samples were found in three different provinces/regions in China. Histopathology confirmed acute and chronic HEV8 infections in the two monkeys. Multiple tissues were positive for HEV RNA and ORF2 proteins. Renal pathology was observed in the monkey with chronic hepatitis. Whole-genome sequencing showed only 1 to 3 mutations in the HEV8 in the fecal samples from the two monkeys compared to that from the camel. HEV8 is circulating in multiple regions in China. Infection of two monkeys with HEV8 induced chronic and systemic infections, demonstrating the high potential zoonotic risk of HEV8.IMPORTANCE It is estimated that one-third of the world population have been exposed to hepatitis E virus (HEV). In developed countries and China, zoonotic HEV strains are responsible for almost all acute and chronic HEV infection cases. It is always of immediate interest to investigate the zoonotic potential of novel HEV strains. In 2016, we discovered a novel HEV genotype, HEV8, in Bactrian camels, but the epidemiology, zoonotic potential, and pathogenicity of the virus were unknown. In the present study, we demonstrated that HEV8 was circulating in multiple regions in China and was capable of infecting cynomolgus macaques, a surrogate for humans, posing high risk of zoonosis. Chronic hepatitis, systemic infection, and renal pathology were observed. Collectively, these data indicate that HEV8 exhibits a high potential for zoonotic transmission. Considering the importance of Bactrian camels as livestock animals, risk groups, such as camelid meat and milk consumers, should be screened for HEV8 infection.
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24
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Denner J. Hepatitis E virus (HEV)-The Future. Viruses 2019; 11:E251. [PMID: 30871152 PMCID: PMC6466233 DOI: 10.3390/v11030251] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 03/05/2019] [Accepted: 03/09/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis (HEV) is widely distributed in pigs and is transmitted with increasing numbers to humans by contact with pigs, contaminated food and blood transfusion. The virus is mostly apathogenic in pigs but may enhance the pathogenicity of other pig viruses. In humans, infection can lead to acute and chronic hepatitis and extrahepatic manifestations. In order to stop the emerging infection, effective counter-measures are required. First of all, transmission by blood products can be prevented by screening all blood donations. Meat and sausages should be appropriately cooked. Elimination of the virus from the entire pork production can be achieved by sensitive testing and elimination programs including early weaning, colostrum deprivation, Caesarean delivery, embryo transfer, treatment with antivirals, protection from de novo infection, and possibly vaccination. In addition, contaminated water, shellfish, vegetables, and fruits by HEV-contaminated manure should be avoided. A special situation is given in xenotransplantation using pig cells, tissues or organs in order to alleviate the lack of human transplants. The elimination of HEV from pigs, other animals and humans is consistent with the One Health concept, preventing subclinical infections in the animals as well as preventing transmission to humans and disease.
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25
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Charre C, Ramière C, Dumortier J, Abravanel F, Lhomme S, Gincul R, Scholtès C. Chronic Genotype 3 Hepatitis E in Pregnant Woman Receiving Infliximab and Azathioprine. Emerg Infect Dis 2019; 24:941-943. [PMID: 29664396 PMCID: PMC5938778 DOI: 10.3201/eid2405.171845] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Acute hepatitis E virus infection during pregnancy has a high fatality rate in developing countries. Little data are available on chronic infection in pregnant women. We report a case of chronic hepatitis E during treatment with infliximab and azathioprine, without adverse event during pregnancy and with spontaneous resolution after delivery.
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26
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Zhang H, Rao H, Wang Y, Wang J, Kong X, Ji Y, Zhu L, Liu Y, Fang J, Yang M, Luo B, Wang Z, Shi Y, Wang Y, Wang H, Zhao J, Wei L. Evaluation of an antigen assay for diagnosing acute and chronic hepatitis E genotype 4 infection. J Gastroenterol Hepatol 2019; 34:458-465. [PMID: 30069920 DOI: 10.1111/jgh.14405] [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: 04/15/2018] [Revised: 06/14/2018] [Accepted: 07/09/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Results obtained from different hepatitis E virus (HEV) tests are usually inconsistent. The detection of serum HEV antigen (Ag) has been suggested to be more sensitive for the diagnosis of genotypes 1 and 3 HEV. METHODS We compared the diagnostic accuracies of serum HEV Ag and HEV RNA by using 202 serum samples from patients suspected acute viral hepatitis. RESULTS The HEV Ag assay was 100% specific. The lower detected levels of viremia ranged from 102 to 103 copies/mL. The sensitivity of the HEV Ag test was 90.5%. One of the 42 cases was negative for anti-HEV IgM, but HEV Ag was still detectable. The detectable period of HEV Ag was in concordance with the detectable period of HEV RNA. Serum HEV Ag was persistently detected in two cases of chronic hepatitis E, confirmed by the persistent presence of HEV RNA despite being negative for anti-HEV IgM. HEV Ag demonstrated good consistency with positive HEV RNA (k = 0.938, P < 0.001). Receiver operating characteristic analysis of HEV Ag suggested a second cut-off value of >0.095 to predict HEV patients with 95.24% sensitivity and 98.75% specificity, and the area under the curve was 0.9887, which was higher than that of three commercial anti-HEV IgM ELISA tests. CONCLUSIONS The presence of HEV Ag has good consistency with HEV RNA in both acute and chronic genotype 4 hepatitis E. HEV Ag is a more promising serum marker to identify active genotype 4 HEV infection than anti-HEV IgM and HEV RNA.
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Affiliation(s)
- Haiying Zhang
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China
| | - Huiying Rao
- Department of Hepatology, Peking University People's Hospital, Beijing, China
| | - Yijin Wang
- Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing, China
| | - Jianghua Wang
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China
| | - Xiangsha Kong
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China
| | - Ying Ji
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China
| | - Ling Zhu
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China
| | - Yan Liu
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China
| | - Jilian Fang
- Department of Hepatology, Peking University People's Hospital, Beijing, China
| | - Ming Yang
- Department of Hepatology, Peking University People's Hospital, Beijing, China
| | - Bifen Luo
- Department of Hepatology, Peking University People's Hospital, Beijing, China
| | - Zhenyu Wang
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China
| | - Yijun Shi
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China
| | - Yu Wang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China
| | - Hao Wang
- Department of Hepatology, Peking University People's Hospital, Beijing, China
| | - Jingmin Zhao
- Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing, China
| | - Lai Wei
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China
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27
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Verma Y. Chronic hepatitis E virus infection by genotype 1-Don't stop looking yet! Indian J Gastroenterol 2018; 37:464-465. [PMID: 30315492 DOI: 10.1007/s12664-018-0904-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Yogita Verma
- Smt B K Shah Medical Institute and Research Centre, Piparia, Waghodia, Vadodara, 391 760, India.
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28
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Nan Y, Wu C, Zhao Q, Sun Y, Zhang YJ, Zhou EM. Vaccine Development against Zoonotic Hepatitis E Virus: Open Questions and Remaining Challenges. Front Microbiol 2018; 9:266. [PMID: 29520257 PMCID: PMC5827553 DOI: 10.3389/fmicb.2018.00266] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Accepted: 02/05/2018] [Indexed: 12/18/2022] Open
Abstract
Hepatitis E virus (HEV) is a fecal-orally transmitted foodborne viral pathogen that causes acute hepatitis in humans and is responsible for hepatitis E outbreaks worldwide. Since the discovery of HEV as a zoonotic agent, this virus has been isolated from a variety of hosts with an ever-expanding host range. Recently, a subunit HEV vaccine developed for the prevention of human disease was approved in China, but is not yet available to the rest of the world. Meanwhile, notable progress and knowledge has been made and revealed in recent years to better understand HEV biology and infection, including discoveries of quasi-enveloped HEV virions and of a new function of the HEV-ORF3 product. However, the impact of these new findings on the development of a protective vaccine against zoonotic HEV infection requires further discussion. In this review, hallmark characteristics of HEV zoonosis, the history of HEV vaccine development, and recent discoveries in HEV virology are described. Moreover, special attention is focused on quasi-enveloped HEV virions and the potential role of the HEV-ORF3 product as antibody-neutralization target on the surface of quasi-enveloped HEV virions to provide new insights for the future development of improved vaccines against zoonotic HEV infection.
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Affiliation(s)
- Yuchen Nan
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Yangling, China
| | - Chunyan Wu
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Yangling, China
| | - Qin Zhao
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Yangling, China
| | - Yani Sun
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Yangling, China
| | - Yan-Jin Zhang
- Molecular Virology Laboratory, VA-MD College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD, United States
| | - En-Min Zhou
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Yangling, China
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Loyrion E, Trouve-Buisson T, Pouzol P, Larrat S, Decaens T, Payen JF. Hepatitis E Virus Infection after Platelet Transfusion in an Immunocompetent Trauma Patient. Emerg Infect Dis 2018; 23:146-147. [PMID: 27983485 PMCID: PMC5176217 DOI: 10.3201/eid2301.160923] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Hepatitis E virus (HEV) infection causes acute liver disease, but severe infections are rare in immunocompetent patients. We describe a case of HEV infection in a previously healthy male trauma patient in France who received massive transfusions. Genotyping confirmed HEV in a transfused platelet pool and the donor.
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30
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Guerra JADAA, Kampa KC, Morsoletto DGB, Junior AP, Ivantes CAP. Hepatitis E: A Literature Review. J Clin Transl Hepatol 2017; 5:376-383. [PMID: 29226104 PMCID: PMC5719195 DOI: 10.14218/jcth.2017.00012] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Revised: 06/27/2017] [Accepted: 07/20/2017] [Indexed: 12/13/2022] Open
Abstract
Hepatitis E is the fifth known form of human viral hepatitis. Although not very common in our clinical practice, the incidence in Western countries is increasing. Infection with the hepatitis E virus (HEV) may be related to acute illness, liver failure, chronic hepatitis and cirrhosis. HEV itself is an RNA virus, with eight described genotypes (HEV 1-8), four of which more commonly affect humans and have, thus, been better studied. Besides liver manifestations, genotype 3 is also related to extra-hepatic manifestations, such as neurological, renal and rheumatological. Evolution to chronic disease occurs especially in patients who underwent transplantation, have hematological malignancies requiring chemotherapy, or have infection with the human immunodeficiency virus. The diagnosis may be difficult because of the low availability of tests and due to low sensibility and specificity. The acute form of illness does not have to be treated, but the chronic one does. We present here a literature review of hepatitis E and the relation between chronic hepatitis E and transplantation.
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Affiliation(s)
- Juliana Ayres de Alencar Arrais Guerra
- Nossa Senhora das Graças Hospital, Alcides Munhoz Street, 433 – Mercês, Curitiba – PR, Brazil
- *Correspondence to: Juliana Ayres de Alencar Arrais Guerra, Nossa Senhora das Graças Hospital, Alcides Munhoz Street, 433 – Mercês, Curitiba – PR 80810-040, Brazil. Tel: +55-41-3240-6060, E-mail:
| | - Katia Cristina Kampa
- Nossa Senhora das Graças Hospital, Alcides Munhoz Street, 433 – Mercês, Curitiba – PR, Brazil
| | | | - Alcindo Pissaia Junior
- Nossa Senhora das Graças Hospital, Alcides Munhoz Street, 433 – Mercês, Curitiba – PR, Brazil
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31
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Nan Y, Wu C, Zhao Q, Zhou EM. Zoonotic Hepatitis E Virus: An Ignored Risk for Public Health. Front Microbiol 2017; 8:2396. [PMID: 29255453 PMCID: PMC5723051 DOI: 10.3389/fmicb.2017.02396] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 11/20/2017] [Indexed: 12/27/2022] Open
Abstract
Hepatitis E virus (HEV) is a quasi-enveloped, single-stranded positive-sense RNA virus. HEV belongs to the family Hepeviridae, a family comprised of highly diverse viruses originating from various species. Since confirmation of HEV's zoonosis, HEV-induced hepatitis has been a public health concern both for developing and developed countries. Meanwhile, the demonstration of a broad host range for zoonotic HEV suggests the existence of a variety of transmission routes that could lead to human infection. Moreover, anti-HEV antibody serosurveillance worldwide demonstrates a higher than expected HEV prevalence rate that conflicts with the rarity and sporadic nature of reported acute hepatitis E cases. In recent years, chronic HEV infection, HEV-related acute hepatic failure, and extrahepatic manifestations caused by HEV infection have been frequently reported. These observations suggest a significant underestimation of the number and complexity of transmission routes previously predicted to cause HEV-related disease, with special emphasis on zoonotic HEV as a public health concern. Significant research has revealed details regarding the virology and infectivity of zoonotic HEV in both humans and animals. In this review, the discovery of HEV zoonosis, recent progress in our understanding of the zoonotic HEV host range, and classification of diverse HEV or HEV-like isolates from various hosts are reviewed in a historic context. Ultimately, this review focuses on current understanding of viral pathogenesis and cross-species transmission of zoonotic HEV. Moreover, host factors and viral determinants influencing HEV host tropism are discussed to provide new insights into HEV transmission and prevalence mechanisms.
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Affiliation(s)
- Yuchen Nan
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Xianyang, China
| | - Chunyan Wu
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Xianyang, China
| | - Qin Zhao
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Xianyang, China
| | - En-Min Zhou
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Xianyang, China
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Barragué H, Condat B, Petitdidier N, Champagne E, Renou C, Izopet J, Abravanel F. Chronic hepatitis E virus infection in a cirrhotic patient: A case report. Medicine (Baltimore) 2017; 96:e7915. [PMID: 28953614 PMCID: PMC5626257 DOI: 10.1097/md.0000000000007915] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
RATIONALE Acute hepatitis E virus (HEV) infections are usually self-limiting in immunocompetent patients. HEV persistence has been described only in immunosuppressed patients such as solid-organ transplant recipients, patients with hematological diseases, or patients with human immunodeficiency virus (HIV) infection. PATIENT CONCERNS A 61-year-old patient was admitted in hospital for jaundice and asthenia. DIAGNOSES The patient had underlying cirrhosis and developed a chronic HEV infection. INTERVENTION Ribavirin therapy was initiated. OUTCOMES Ribavirin therapy for 12 months allowed the clearance of the virus and HEV viral load remained undetectable thereafter. This patient had taken no immunosuppressive drugs, was not suffering from any autoimmune disease and was not infected with HIV. We studied the patient's anti-HEV immune response months after the viral clearance. His peripheral blood mononuclear cells (PBMC) were stimulated in vitro by HEV peptides. The patient had a mild T lymphopenia, but polyclonal stimulation of PBMC showed a robust T cell response. The response of his anti-HEV specific interferon-γ producing T cells was low. LESSONS Other studies are now needed to identify the population with a chronic evolution of HEV infection despite no apparent immunodepression.
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Affiliation(s)
- Hugo Barragué
- Centre de Physiopathologie de Toulouse Purpan, INSERM U1043/CNRS UMR5282/Université Toulouse III Paul-Sabatier, Toulouse
| | | | | | - Eric Champagne
- Centre de Physiopathologie de Toulouse Purpan, INSERM U1043/CNRS UMR5282/Université Toulouse III Paul-Sabatier, Toulouse
| | | | - Jacques Izopet
- Centre de Physiopathologie de Toulouse Purpan, INSERM U1043/CNRS UMR5282/Université Toulouse III Paul-Sabatier, Toulouse
- Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Laboratoire de virologie, Centre National de Référence Hépatite E, Institut fédératif de biologie de Purpan, Toulouse, France
| | - Florence Abravanel
- Centre de Physiopathologie de Toulouse Purpan, INSERM U1043/CNRS UMR5282/Université Toulouse III Paul-Sabatier, Toulouse
- Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Laboratoire de virologie, Centre National de Référence Hépatite E, Institut fédératif de biologie de Purpan, Toulouse, France
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Ankcorn MJ, Tedder RS. Hepatitis E: the current state of play. Transfus Med 2017; 27:84-95. [PMID: 28382704 DOI: 10.1111/tme.12405] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 11/08/2016] [Accepted: 02/22/2017] [Indexed: 12/16/2022]
Abstract
The hepatitis E virus (HEV) is a major cause of acute hepatitis globally. Genotypes 1 and 2 (G1 and G2) are obligate human pathogens transmitted faeco-orally, leading to epidemics in developing countries. In contrast, genotypes 3 and 4 (G3 and G4) have a wider host range, including humans, but are primarily porcine viruses and are transmitted from animals to humans as a food-borne zoonosis when meat from an infected animal is consumed. HEV is increasingly recognised as a problem in developed countries, including countries in Europe. G3 HEV is now the most common cause of acute viral hepatitis in the UK and cases continue to rise. The majority of these infections are acquired within the UK and thought to be from insufficiently cooked meat, predominantly processed pork meat. Previously thought to only cause self-limiting disease, HEV infection can persist in immunosuppressed patients, which may lead to chronic hepatitis and the rapid development of cirrhosis. Of particular interest to the transfusion community has been the possibility of transfusion-transmitted HEV, which has been reported from countries classically considered HEV-endemic but also non-endemic countries in Europe and Japan. This has prompted some countries to introduce screening for HEV in blood donations.
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Affiliation(s)
- M J Ankcorn
- Blood Borne Virus Unit, Virus Reference Department, National Infection Service, Public Health England, London, UK.,Transfusion Microbiology, National Health Service Blood and Transplant, London, UK
| | - R S Tedder
- Blood Borne Virus Unit, Virus Reference Department, National Infection Service, Public Health England, London, UK.,Transfusion Microbiology, National Health Service Blood and Transplant, London, UK
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Calisti G, Irish DN, Ijaz S, Tedder RS, Moore K. Acute hepatitis E mimicking a flare of disease in a patient with chronic autoimmune hepatitis. Ann Hepatol 2017; 16:160-163. [PMID: 28051806 DOI: 10.5604/16652681.1226952] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Acute hepatitis E is becoming increasingly recognised in Europe with up to 40% of the population in Southern France being exposed to the virus, which is harboured in pigs. Patients with known liver disease may present with acute hepatitis E and present a diagnostic challenge. For example patients with autoimmune hepatitis (AIH) who are immunosuppressed and contract hepatitis E may be at increased risk of developing chronicity due to concurrent immunosuppression. Importantly, the diagnosis may be missed with the infection misdiagnosed as an autoimmune flare, and immunosuppression increased by the attending physician, thus enhancing the risk of chronicity of infection leading to progressive liver injury in immunocompromised patients. We report a case of acute hepatitis E in a patient with AIH and discuss the features that helped us differentiating it from an autoimmune flare.
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Affiliation(s)
- Giorgio Calisti
- Department of Virology, Royal Free London NHS Foundation Trust, London, United Kingdom
| | - Dianne N Irish
- Department of Virology, Royal Free London NHS Foundation Trust, London, United Kingdom
| | - Samreen Ijaz
- Blood Borne Virus Unit, MS-Colindale, Public Health England, London, United Kingdom
| | - Richard S Tedder
- Blood Borne Virus Unit, MS-Colindale, Public Health England, London, United Kingdom
| | - Kevin Moore
- Centre for Hepatology, Royal Free and University College Medical School, University College London, United Kingdom
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35
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Nan Y, Zhang YJ. Molecular Biology and Infection of Hepatitis E Virus. Front Microbiol 2016; 7:1419. [PMID: 27656178 PMCID: PMC5013053 DOI: 10.3389/fmicb.2016.01419] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Accepted: 08/26/2016] [Indexed: 12/13/2022] Open
Abstract
Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus.
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Affiliation(s)
- Yuchen Nan
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F UniversityYangling, China; Molecular Virology Laboratory, VA-MD College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, College ParkMD, USA
| | - Yan-Jin Zhang
- Molecular Virology Laboratory, VA-MD College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, College Park MD, USA
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36
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Vestergaard HT, Joergensen CS, Ott P, Frische A. HEPATITIS E – Reaction or unspecific reaction? J Clin Virol 2016. [DOI: 10.1016/j.jcv.2016.08.160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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37
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Fraticelli P, Bagnarelli P, Tarantino G, Martino GP, Benfaremo D, Nobili L, Mandolesi A, Barbisan F, Marinelli K, Mattioli M, Murri M, Gabrielli A. Chronic hepatitis E in a patient treated with rituximab and mycophenolate mofetil for Sjögren's syndrome. Rheumatology (Oxford) 2016; 55:2275-2277. [PMID: 27498353 DOI: 10.1093/rheumatology/kew282] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Revised: 06/20/2016] [Indexed: 11/12/2022] Open
Affiliation(s)
| | | | | | | | | | | | - Alessandra Mandolesi
- Anatomia Patologica, Dipartimento di Scienze Biomediche e Sanità Pubblica, Università Politecnica delle Marche, Ancona, Italy
| | - Francesca Barbisan
- Anatomia Patologica, Dipartimento di Scienze Biomediche e Sanità Pubblica, Università Politecnica delle Marche, Ancona, Italy
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38
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Pérez-Gracia MT, Suay-García B, García M, Mateos-Lindemann ML. Hepatitis E: latest developments in knowledge. Future Microbiol 2016; 11:789-808. [PMID: 27203841 DOI: 10.2217/fmb-2016-0012] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Hepatitis E, caused by Hepatitis E virus (HEV), is a highly prevalent disease in developing countries. In developed nations, autochthonous HEV infections seem to be an emergent disease. Its clinical manifestations and epidemiology are well known for endemic countries. It has been confirmed that hepatitis E is a zoonosis and that parenteral transmission can also occur. The molecular mechanisms of HEV replication are not fully understood, mostly because there are no efficient cell culture systems. HEV can cause chronic hepatitis in organ transplant recipients and immunocompetent patients. Cases with fulminant hepatitis and other extrahepatic manifestations have also been reported. The diagnosis is based on serological studies and detection of HEV RNA in blood and feces. Treatment with ribavirin and/or pegylated-IFN-α have proven to be successful in some cases. The recently approved/marketed vaccine is a good option in order to prevent this infection.
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Affiliation(s)
- M Teresa Pérez-Gracia
- Área de Microbiología, Departamento de Farmacia, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avenida Seminario s/n 46113, Moncada, Valencia, Spain
| | - Beatriz Suay-García
- Área de Microbiología, Departamento de Farmacia, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avenida Seminario s/n 46113, Moncada, Valencia, Spain
| | - Mario García
- Área de Microbiología, Departamento de Farmacia, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avenida Seminario s/n 46113, Moncada, Valencia, Spain
| | - M Luisa Mateos-Lindemann
- Unidad de Virología, Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Ctra. Colmenar Km 9,1, Madrid 28034, Spain
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39
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Lei Q, Li L, Cai J, Huang W, Qin B, Zhang S. ORF3 of Hepatitis E Virus Inhibits the Expression of Proinflammatory Cytokines and Chemotactic Factors in LPS-Stimulated Human PMA-THP1 Cells by Inhibiting NF-κB Pathway. Viral Immunol 2016; 29:105-11. [PMID: 26771290 DOI: 10.1089/vim.2015.0107] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Hepatitis E virus (HEV) is one of the primary causative agents of acute hepatitis. It is noteworthy that HEV can develop chronic infection and even lead to liver cirrhosis; however, the mechanism has not been revealed. In this study, the ELISA assay was used to detect protein levels, and we found that HEV open reading frame 3 (ORF3) protein inhibited the expression of proinflammatory cytokines (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-1β, IL-6, IL-8, IL-12p40, and IL-18) and chemotactic factors (nitric oxide [NO], interferon-inducible protein-10 (IP-10), macrophage inflammatory protein (MIP)-1α, monocyte chemoattractant protein-1 (MCP-1), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF)] in lipopolysaccharide (LPS)-stimulated human PMA-THP1 cells. Further study showed that mRNA and protein levels of pattern recognition receptors (PRRs), such as Toll-like receptor 4 (TLR4), TNF receptor-associated factor 6 (TRAF6), and nucleotide-binding oligomerization domain containing 2 (NOD2), decreased after infection of pLL3.7-ORF3 (pORF3); moreover, the inhibition produced corresponding upregulation of IκBα and downregulation of phosphorylated IκB kinase IKKɛ (p-IKKɛ) and phosphorylated nuclear factor (NF)-κB (p-NF-κB), but little variation was found in the concentration of IKKɛ and NF-κB. Taken together, our results demonstrated that HEV ORF3 attenuated LPS-induced cytokine production and chemotactic factors, predominantly by inhibiting various PRRs-mediated NF-κB signaling pathways. The anti-inflammatory properties might be of great importance to clarify the role and mechanism of macrophages in chronic HEV infection and cirrhosis.
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Affiliation(s)
- Qingsong Lei
- Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China
| | - Lin Li
- Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China
| | - Jia Cai
- Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China
| | - Wenxiang Huang
- Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China
| | - Bo Qin
- Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China
| | - Shujun Zhang
- Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China
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40
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Sayed IM, Vercouter AS, Abdelwahab SF, Vercauteren K, Meuleman P. Is hepatitis E virus an emerging problem in industrialized countries? Hepatology 2015; 62:1883-92. [PMID: 26175182 DOI: 10.1002/hep.27990] [Citation(s) in RCA: 89] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Accepted: 07/13/2015] [Indexed: 02/05/2023]
Abstract
Hepatitis E virus (HEV) is yearly responsible for approximately 20 million infections worldwide. Although most infections occur in developing countries, HEV appears to be an emerging problem in several industrialized countries, where it is mostly associated with either traveling to an HEV endemic area or contact with pigs, which represent a major reservoir of HEV. The major risk groups for HEV infection and its ensuing complications are elderly men, pregnant women, young children, immunocompromised patients, patients with preexisting liver disease, and workers that come into close contact with HEV-infected animals. Whereas HEV mainly causes acute self-limiting infections, chronic infections may occur among immunocompromised patients (e.g., transplant recipients and human immunodeficiency virus [HIV]-infected patients). Accordingly, HEV-HIV coinfection leads to accelerated liver cirrhosis and increased mortality rates compared to HEV infection alone, which is, except during pregnancy, usually associated with only low mortality. In the Western world, the most common genotype (gt) causing HEV infection is gt 3. Ribavirin (RBV) and interferon have been used successfully for treatment of HEV, but this treatment is contraindicated in certain patient groups. Therefore, novel antiviral compounds are highly needed, especially given that viral isolates with RBV resistance have been recently identified. Moreover, eradication of HEV is hampered by long-term environmental persistence of the virus, which represents a continuous source of the virus. In 2011, the first prophylactic HEV vaccine, Hecolin, was approved in China, but it is not yet globally available. In this review, we will discuss the molecular virology of HEV, mode of transmission in industrialized countries, and potential implications for different specific patient populations.
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Affiliation(s)
- Ibrahim M Sayed
- Center for Vaccinology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Gent, Belgium
- Microbiology and Immunology Department, Faculty of Medicine, Assuit University, Assuit, Egypt
| | - Ann-Sofie Vercouter
- Center for Vaccinology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Gent, Belgium
| | - Sayed F Abdelwahab
- Microbiology and Immunology Department, Faculty of Medicine, Minia University, Minia, Egypt
- Microbiology Department, College of Pharmacy, Taif University, Taif, Saudi Arabia
| | - Koen Vercauteren
- Center for Vaccinology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Gent, Belgium
| | - Philip Meuleman
- Center for Vaccinology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Gent, Belgium
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41
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Lee GY, Poovorawan K, Intharasongkroh D, Sa-nguanmoo P, Vongpunsawad S, Chirathaworn C, Poovorawan Y. Hepatitis E virus infection: Epidemiology and treatment implications. World J Virol 2015; 4:343-355. [PMID: 26568916 PMCID: PMC4641226 DOI: 10.5501/wjv.v4.i4.343] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2015] [Revised: 08/06/2015] [Accepted: 09/18/2015] [Indexed: 02/05/2023] Open
Abstract
Hepatitis E virus (HEV) infection is now established as an emerging enteric viral hepatitis. Standard treatments in acute and chronic hepatitis E remain to be established. This study undertakes a review of the epidemiology, treatment implication and vaccine prevention from published literature. HEV infection is a worldwide public health problem and can cause acute and chronic hepatitis E. HEV genotypes 1 and 2 are primarily found in developing countries due to waterborne transmission, while the zoonotic potential of genotypes 3 and 4 affects mostly industrialized countries. An awareness of HEV transmission through blood donation, especially in the immunocompromised and solid organ transplant patients, merits an effective anti-viral therapy. There are currently no clear indications for the treatment of acute hepatitis E. Despite concerns for side effects, ribavirin monotherapy or in combination with pegylated interferon alpha for at least 3 mo appeared to show significant efficacy in the treatment of chronic hepatitis E. However, there are no available treatment options for specific patient population groups, such as women who are pregnant. Vaccination and screening of HEV in blood donors are currently a global priority in managing infection. New strategies for the treatment and control of hepatitis E are required for both acute and chronic infections, such as prophylactic use of medications, controlling large outbreaks, and finding acceptable antiviral therapy for pregnant women and other patient groups for whom the current options of treatment are not viable.
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Zhao C, Geng Y, Harrison TJ, Huang W, Song A, Wang Y. Evaluation of an antigen-capture EIA for the diagnosis of hepatitis E virus infection. J Viral Hepat 2015; 22:957-63. [PMID: 25732029 DOI: 10.1111/jvh.12397] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2014] [Accepted: 01/02/2015] [Indexed: 12/12/2022]
Abstract
An enzyme immunoassay (EIA) has been developed for hepatitis E virus (HEV) antigen (HEV-Ag) detection and marketed in China. This study aimed to evaluate the sensitivity of the assay and assess the value of HEV-Ag detection in the diagnosis of HEV infection in comparison with HEV RNA detection. Using serial dilutions of a genotype 4 HEV strain, significant correlation was found between the EIA (S/CO) and HEV RNA (IU/mL) concentration in the range 10(3.5) to 10(0.5) IU/mL HEV RNA, the Pearson correlation coefficient r approached 0.97. The EIA detection limit was 54.6 IU/mL, compared to 24 IU/mL for HEV RNA using real-time RT-PCR. In clinical samples from hepatitis E patients, the HEV-Ag and HEV RNA positivity rates were 55.6% (65/117) and 60.7% (71/117) in sera and 76.7% (56/73) and 84.9% (62/73) in stools, and the concordance of these two markers was 77.8% in sera and 80.8% in stools. In serum samples, the HEV-Ag positivity rate and the concordance between HEV-Ag and HEV RNA were inversely proportional to the presence of anti-HEV antibody. The presence of anti-HEV IgG could reduce the S/CO of the HEV-Ag EIA. These results reveal a significant correlation between the detection of HEV-Ag and HEV RNA. The sensitivity of the HEV-Ag EIA was lower than real-time RT-PCR but could be higher than conventional nested RT-PCR. Therefore, the detection of HEV-Ag in serum and faeces is valuable for the diagnosis and prognosis of HEV infection in developing regions where real-time RT-PCR is not available.
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Affiliation(s)
- C Zhao
- College of Life Sciences, Jilin University, Changchun, China
- Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing, China
| | - Y Geng
- Health Science Center, Hebei University, Baoding, China
| | - T J Harrison
- Division of Medicine, University College London Medical School, London, UK
| | - W Huang
- College of Life Sciences, Jilin University, Changchun, China
| | - A Song
- College of Life Sciences, Jilin University, Changchun, China
| | - Y Wang
- College of Life Sciences, Jilin University, Changchun, China
- Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing, China
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Chronic hepatitis E in solid-organ transplantation: the key implications of immunosuppressants. Curr Opin Infect Dis 2015; 27:303-8. [PMID: 24977682 DOI: 10.1097/qco.0000000000000074] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW Solid-organ recipients infected with hepatitis E virus (HEV) bear an extremely high risk of developing chronic hepatitis, although this virus only causes acute infection in the general population. Immunosuppressive medication universally used after transplantation to prevent organ rejection appears to be a main risk factor for developing chronic infection. This review aims to overview and emphasize the current clinical and experimental evidence regarding the key implications of immunosuppressants in chronic hepatitis E. RECENT FINDINGS Over 60% of organ recipients who are infected with HEV develop chronic hepatitis. Immunosuppressant treatment after transplantation was identified as a key risk factor. Therefore, dose reduction or even withdrawal of immunosuppressants is considered as the first intervention strategy to achieve viral clearance in these patients. Otherwise, ribavirin, as an off-label medication, is considered as an antiviral treatment, with compelling outcomes observed so far. Interestingly, in addition to a common immunosuppression property that can favour HEV infection in general, different types of immunosuppressants may exert differential impacts on the infection course in patients. Furthermore, potential interaction may exist between particular immunosuppressant and ribavirin. With the recent development of a cell culture system for HEV, experimental research has been initiated to investigate how immunosuppressive drugs interact with HEV infection. SUMMARY On the basis of the current evidence, it remains impossible to define an optimal immunosuppressive protocol for these HEV-infected patients. However, the realization of this clinical issue and the initiation of translational research using cell culture models of HEV have been represented as milestones in this field.
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44
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Murali AR, Kotwal V, Chawla S. Chronic hepatitis E: A brief review. World J Hepatol 2015; 7:2194-2201. [PMID: 26380044 PMCID: PMC4561773 DOI: 10.4254/wjh.v7.i19.2194] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 07/28/2015] [Accepted: 08/21/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E viral infection has traditionally been considered an acute, self-limited, water borne disease similar to hepatitis A, endemic to developing countries. However, over the past decade, zoonotic transmission and progression to chronicity in human patients has been identified, resulting in persistently elevated transaminase levels, progressive liver injury and cirrhosis. In addition to liver injury, neurological, renal and rheumatological manifestations have also been reported. Chronic hepatitis E occurs mainly in immunosuppressed individuals such as transplant recipients, human immunodeficiency virus patients with low CD4 counts and in patients with hematological malignancies receiving chemotherapy. Diagnosis is established by persistent elevation of hepatitis E virus RNA in the stool or serum. This population often requires treatment with antiviral agents, particularly ribavirin, as spontaneous clearance with reduction in immunosuppression occurs only in about a third of the patients. The purpose of this review, is to further discuss the clinical presentation, and recent advances in diagnosis, treatment and prophylaxis of chronic hepatitis E.
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45
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Suzuki K, Kataoka K, Miyamoto Y, Miyasaka A, Kumagai I, Takikawa Y, Takahashi M, Okamoto H. Clinical and molecular analyses of sporadic acute hepatitis A and E and the specific viral genotypes isolated in Iwate and three neighboring prefectures in the northern part of Honshu, Japan, between 2004 and 2013. Hepatol Res 2015; 45:714-727. [PMID: 25146162 DOI: 10.1111/hepr.12406] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Revised: 07/31/2014] [Accepted: 08/19/2014] [Indexed: 02/08/2023]
Abstract
AIM To examine the prevalence and characteristics of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections in the northern part of Honshu, Japan, during the last decade. METHODS Using the registration system of a prospective cohort study for acute liver injury (ALI) in Iwate and three neighboring prefectures, we examined the prevalence of sporadic acute hepatitis (AH) with HAV (AH-A) and HEV (AH-E) and the distribution of viral genotypes in 487 patients diagnosed with ALI between 2004 and 2013. RESULTS Among all 487 patients, 135 (28%) had ALI with viral infection. In the cases with viral ALI, the prevalence of hepatitis B virus-related AH was highest (55.6%). AH-E was seen in 23 patients (17.0%) and its prevalence was higher than that of AH-A (10 patients, 7.4%). There were no appreciable differences in the prevalence of AH-A and AH-E between 2004-2008 and 2009-2013. However, subgenotype IIIA HAV homologous to Korean strains has recently emerged, and the number of AH-E cases seems to be increasing. HEV genotype 3 was predominant throughout the observation period, but HEV genotype 4 was found in three patients after 2010. The transmission routes of HAV and HEV infections were unknown in approximately 60% of the patients. CONCLUSION In the northern part of Honshu, Japan, HEV has been more frequently implicated in the development of AH than HAV, and HEV genotype 4 has been recently increasing. To provide an effective prophylactic management for HAV and HEV infections, further clarification of the transmission routes is needed.
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Affiliation(s)
- Kazuyuki Suzuki
- Department of Nutritional Science, Morioka University, Morioka, Japan.,Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Kojiro Kataoka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Yasuhiro Miyamoto
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Akio Miyasaka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Ichiro Kumagai
- Department of Internal Medicine, Morioka City Hospital, Morioka, Japan
| | - Yasuhiro Takikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke, Japan
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Lee JH, Choi SB, Jin M, Lee JH, Han SD, Bae H, Lim I, Noh YH. Euglycemia in Diabetic Rats Leads to Reduced Liver Weight via Increased Autophagy and Apoptosis through Increased AMPK and Caspase-3 and Decreased mTOR Activities. J Diabetes Res 2015; 2015:497431. [PMID: 26060824 PMCID: PMC4427805 DOI: 10.1155/2015/497431] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2014] [Revised: 03/11/2015] [Accepted: 03/31/2015] [Indexed: 01/14/2023] Open
Abstract
Euglycemia is the ultimate goal in diabetes care to prevent complications. However, the benefits of euglycemia in type 2 diabetes are controversial because near-euglycemic subjects show higher mortality than moderately hyperglycemic subjects. We previously reported that euglycemic-diabetic rats on calorie-control lose a critical liver weight (LW) compared with hyperglycemic rats. Here, we elucidated the molecular mechanisms underlying the loss of LW in euglycemic-diabetic rats and identified a potential risk in achieving euglycemia by calorie-control. Sprague-Dawley diabetic rats generated by subtotal-pancreatectomy were fed a calorie-controlled diet for 7 weeks to achieve euglycemia using 19 kcal% (19R) or 6 kcal% (6R) protein-containing chow or fed ad libitum (19AL). The diet in both R groups was isocaloric/kg body weight to the sham-operated group (19S). Compared with 19S and hyperglycemic 19AL, both euglycemic R groups showed lower LWs, increased autophagy, and increased AMPK and caspase-3 and decreased mTOR activities. Though degree of insulin deficiency was similar among the diabetic rats, Akt activity was lower, and PTEN activity was higher in both R groups than in 19AL whose signaling patterns were similar to 19S. In conclusion, euglycemia achieved by calorie-control is deleterious in insulin deficiency due to increased autophagy and apoptosis in the liver via AMPK and caspase-3 activation.
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Affiliation(s)
- Jun-Ho Lee
- Department of Biochemistry, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea
| | - Soo-Bong Choi
- Department of Internal Medicine, School of Medicine, Konkuk University, Chungju Hospital, 82 Kukwondae-ro, Chungju 380-704, Republic of Korea
| | - Mingli Jin
- Department of Biochemistry, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea
| | - Ju-Han Lee
- Department of Biochemistry, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea
- Rmedica-Stem Cell, 98 Gasan Digital 2-ro, Geumcheon-gu, Seoul 153-768, Republic of Korea
| | - Sang-Don Han
- Department of Neurology, School of Medicine, Konkuk University, Chungju Hospital, 82 Kukwondae-ro, Chungju 380-704, Republic of Korea
| | - Hyemi Bae
- Department of Physiology, College of Medicine, Chung-Ang University, 84 Heukseouk-ro, Dongjak-gu, Seoul 156-861, Republic of Korea
| | - Inja Lim
- Department of Physiology, College of Medicine, Chung-Ang University, 84 Heukseouk-ro, Dongjak-gu, Seoul 156-861, Republic of Korea
| | - Yun-Hee Noh
- Department of Biochemistry, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea
- *Yun-Hee Noh:
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Sebode M, Pischke S, Lütgehetmann M, Polywka S, Quaas A, Lohse AW, Wege H. New foe treated with old guns - supportive role of steroids in the treatment of acute severe hepatitis E. BMC Gastroenterol 2014; 14:191. [PMID: 25398314 PMCID: PMC4236436 DOI: 10.1186/s12876-014-0191-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2014] [Accepted: 10/20/2014] [Indexed: 12/17/2022] Open
Abstract
Background Autochthonous hepatitis E has been observed with growing incidence in industrialized countries. Hepatitis E virus infection causes an acute hepatitis with spontaneous resolution in the majority of cases. However, in individual cases, hepatitis E may lead to life-threatening acute liver failure. In this report, we describe a case of acute liver injury caused by an autochthonous hepatitis E that resolved under steroid treatment. To our knowledge, this is the first case report describing supportive steroid monotherapy for acute liver injury due to hepatitis E. Case presentation A 63-year-old Caucasian male presented with acute liver injury of unknown origin. After excluding the most prevalent causes of acute liver injury, liver histology revealed signs of immune-mediated toxic or drug-induced liver injury. Therefore, immunosuppressive treatment with prednisolone was started. After initialization of steroid treatment, polymerase chain reaction analyses of peripheral blood and liver tissue revealed an acute hepatitis E virus infection (genotype 3). Under sustained steroid treatment, acute liver injury improved and hepatitis E infection resolved. Conclusion Steroid treatment might be an option to prevent progress of life-threatening liver failure and liver transplantation in patients with hepatitis E-induced acute liver injury and high-grade inflammation.
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Höner zu Siederdissen C, Pischke S, Schlue J, Deterding K, Hellms T, Schuler-Lüttmann S, Schwarz A, Manns MP, Cornberg M, Wedemeyer H. Chronic hepatitis E virus infection beyond transplantation or human immunodeficiency virus infection. Hepatology 2014; 60:1112-3. [PMID: 24375747 DOI: 10.1002/hep.26987] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2013] [Revised: 12/02/2013] [Accepted: 12/19/2013] [Indexed: 12/26/2022]
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Kamar N, Izopet J. Does chronic hepatitis E virus infection exist in immunocompetent patients? Hepatology 2014; 60:427. [PMID: 24214924 DOI: 10.1002/hep.26927] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2013] [Accepted: 09/16/2013] [Indexed: 01/21/2023]
Affiliation(s)
- Nassim Kamar
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France; INSERM U1043, CHU Purpan, Toulouse, France; Université Paul Sabatier, Toulouse, France
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SPF rabbits infected with rabbit hepatitis E virus isolate experimentally showing the chronicity of hepatitis. PLoS One 2014; 9:e99861. [PMID: 24937350 PMCID: PMC4061063 DOI: 10.1371/journal.pone.0099861] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 05/13/2014] [Indexed: 12/19/2022] Open
Abstract
This study focused on investigating the pathogenesis seen in specific-pathogen-free (SPF) rabbits following infection with a homologous rabbit HEV isolate (CHN-BJ-rb14) and comparing it to that seen following infection with a heterologous swine genotype 4 HEV isolate (CHN-XJ-SW13). Three of the four animals inoculated with the homologous rabbit HEV became infected, exhibiting an intermittent viremia, obvious fluctuations of liver function biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and persistent fecal virus shedding throughout the nine month study. In addition, liver histopathology showed both chronic inflammation and some degree of fibrosis. Both positive and negative-stranded HEV RNA and HEV antigen expression were detected in liver, brain, stomach, duodenum and kidney from the necropsied rabbits. Inflammation of extrahepatic tissue (duodenum and kidney) was also observed. Three of the four rabbits inoculated with the heterologous genotype 4 swine HEV also became infected, showing similar levels of anti-HEV antibody to that generated following infection with the homologous virus isolate. The duration of both viremia and fecal shedding of virus was however shorter following infection with the heterologous virus and there was no significant elevation of liver function biomarkers. These results suggest that rabbit HEV infection may cause more severe hepatitis and prolong the course of the disease, with a possible chronic trend of hepatitis in SPF rabbits.
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