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Brüggemann Y, Klöhn M, Wedemeyer H, Steinmann E. Hepatitis E virus: from innate sensing to adaptive immune responses. Nat Rev Gastroenterol Hepatol 2024; 21:710-725. [PMID: 39039260 DOI: 10.1038/s41575-024-00950-z] [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] [Accepted: 05/29/2024] [Indexed: 07/24/2024]
Abstract
Hepatitis E virus (HEV) infections are a major cause of acute viral hepatitis in humans worldwide. In immunocompetent individuals, the majority of HEV infections remain asymptomatic and lead to spontaneous clearance of the virus, and only a minority of individuals with infection (5-16%) experience symptoms of acute viral hepatitis. However, HEV infections can cause up to 30% mortality in pregnant women, become chronic in immunocompromised patients and cause extrahepatic manifestations. A growing body of evidence suggests that the host immune response to infection with different HEV genotypes is a critical determinant of distinct HEV infection outcomes. In this Review, we summarize key components of the innate and adaptive immune responses to HEV, including the underlying immunological mechanisms of HEV associated with acute and chronic liver failure and interactions between T cell and B cell responses. In addition, we discuss the current status of vaccines against HEV and raise outstanding questions regarding the immune responses induced by HEV and treatment of the disease, highlighting areas for future investigation.
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Affiliation(s)
- Yannick Brüggemann
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
| | - Mara Klöhn
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Partner Sites Hannover-Braunschweig, Hannover, Germany
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
| | - Eike Steinmann
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany.
- German Center for Infection Research (DZIF), External Partner Site, Bochum, Germany.
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Solignac J, Boschi C, Pernin V, Fouilloux V, Motte A, Aherfi S, Fabre-Aubrespy M, Legris T, Brunet P, Colson P, Moal V. The question of screening organ donors for hepatitis e virus: a case report of transmission by kidney transplantation in France and a review of the literature. Virol J 2024; 21:136. [PMID: 38867299 PMCID: PMC11167830 DOI: 10.1186/s12985-024-02401-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 05/28/2024] [Indexed: 06/14/2024] Open
Abstract
BACKGROUND Hepatitis E is a potentially serious infection in organ recipients, with an estimated two-thirds of cases becoming chronic, and with a subsequent risk of cirrhosis and death. In Europe, transmission occurs most often through the consumption of raw or undercooked pork, more rarely through blood transfusion, but also after solid organ transplantation. Here we describe a case of Hepatitis E virus (HEV) infection transmitted following kidney transplantation and review the literature describing cases of HEV infection transmitted by solid organ transplantation. CASE PRESENTATION Three weeks after kidney transplantation, the patient presented with an isolated minimal increase in GGT and hepatic cytolysis 6 months later, leading to the diagnosis of genotype 3c hepatitis E, with a plasma viral load of 6.5 log10IU/mL. In retrospect, HEV RNA was detected in the patient's serum from the onset of hepatitis, and in the donor's serum on the day of donation, with 100% identity between the viral sequences, confirming donor-derived HEV infection. Hepatitis E had a chronic course, was treated by ribavirin, and relapsed 10 months after the end of treatment. DISCUSSION Seven cases of transmission of HEV by solid organ transplantation have been described since 2012 without systematic screening for donors, all diagnosed at the chronic infection stage; two patients died. HEV organ donor transmission may be underestimated and there is insufficient focus on immunocompromised patients in whom mild liver function test impairment is potentially related to hepatitis E. However, since HEV infection is potentially severe in these patients, and as evidence accumulates, we believe that systematic screening of organ donors should be implemented for deceased and living donors regardless of liver function abnormalities, as is already the case in the UK and Spain. In January 2024, the French regulatory agency of transplantation has implemented mandatory screening of organ donors for HEV RNA.
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Affiliation(s)
- Justine Solignac
- Centre de Néphrologie Et Transplantation Rénale, Aix Marseille Université, Publique Hôpitaux de Marseille, Hôpital Conception, 147 Boulevard Baille, 13005, Marseille, France
| | - Celine Boschi
- IHU Méditerranée Infection, Publique Hôpitaux de Marseille, 19-21 Boulevard Jean Moulin, 13005, Marseille, France
- Aix Marseille Université, Institut de Recherche Et Développement, Microbes Evolution Phylogeny and Infections, 27 Boulevard Jean Moulin, 13005, Marseille, France
| | - Vincent Pernin
- Department of Nephrology Dialysis and Kidney Transplantation, Lapeyronie University Hospital, Montpellier, France
- Institute for Regenerative Medicine and Biotherapy (IRMB), Montpellier, France
| | - Virginie Fouilloux
- Department of Congenital and Pediatric Cardiac Surgery, Timone Children's Hospital, Marseille, France
| | - Anne Motte
- IHU Méditerranée Infection, Publique Hôpitaux de Marseille, 19-21 Boulevard Jean Moulin, 13005, Marseille, France
- Aix Marseille Université, Institut de Recherche Et Développement, Microbes Evolution Phylogeny and Infections, 27 Boulevard Jean Moulin, 13005, Marseille, France
| | - Sarah Aherfi
- IHU Méditerranée Infection, Publique Hôpitaux de Marseille, 19-21 Boulevard Jean Moulin, 13005, Marseille, France
- Aix Marseille Université, Institut de Recherche Et Développement, Microbes Evolution Phylogeny and Infections, 27 Boulevard Jean Moulin, 13005, Marseille, France
| | - Maxime Fabre-Aubrespy
- Department of Orthopaedic Surgery, Sainte-Marguerite University Hospital, Marseille, France
| | - Tristan Legris
- Centre de Néphrologie Et Transplantation Rénale, Publique Hôpitaux de Marseille, Hôpital Conception, Marseille, France
| | - Philippe Brunet
- Centre de Néphrologie Et Transplantation Rénale, Aix Marseille Université, Publique Hôpitaux de Marseille, Hôpital Conception, 147 Boulevard Baille, 13005, Marseille, France
| | - Philippe Colson
- IHU Méditerranée Infection, Publique Hôpitaux de Marseille, 19-21 Boulevard Jean Moulin, 13005, Marseille, France
- Aix Marseille Université, Institut de Recherche Et Développement, Microbes Evolution Phylogeny and Infections, 27 Boulevard Jean Moulin, 13005, Marseille, France
| | - Valérie Moal
- Centre de Néphrologie Et Transplantation Rénale, Aix Marseille Université, Publique Hôpitaux de Marseille, Hôpital Conception, 147 Boulevard Baille, 13005, Marseille, France.
- Aix Marseille Université, Institut de Recherche Et Développement, Microbes Evolution Phylogeny and Infections, 27 Boulevard Jean Moulin, 13005, Marseille, France.
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Boonyai A, Thongput A, Sisaeng T, Phumchan P, Horthongkham N, Kantakamalakul W, Chaimayo C. Prevalence and clinical correlation of hepatitis E virus antibody in the patients' serum samples from a tertiary care hospital in Thailand during 2015-2018. Virol J 2021; 18:145. [PMID: 34247642 PMCID: PMC8273939 DOI: 10.1186/s12985-021-01616-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 07/02/2021] [Indexed: 02/02/2023] Open
Abstract
Background Prevalence and incidence of hepatitis caused by HEV infection are usually higher in developing countries. This study demonstrated the HEV seroprevalence and incidence of HEV infection in patients with clinical hepatitis in a tertiary hospital in Thailand. Methods A laboratory-based cross-sectional study was conducted using 1106 serum samples from patients suspected of HEV infection sent to the Serology laboratory, Siriraj Hospital, for detecting HEV antibodies during 2015–2018. Prevalence of anti-HEV IgG and IgM antibodies in general patients, including organ transplant recipients and pregnant women in a hospital setting, were determined using indirect enzyme-linked immunosorbent assay (ELISA) kits. Comparison of laboratory data between groups with different HEV serological statuses was performed. Results HEV IgG antibodies were detected in 40.82% of 904 serum samples, while HEV IgM antibodies were detected in 11.75% of 1081 serum samples. Similar IgG and IgM antibody detection rates were found in pregnant women. Interestingly, anti-HEV IgM antibodies were detected in 38.5% of patients who underwent organ transplantation. Patients who tested positive for anti-HEV IgM antibodies had higher alanine aminotransferase levels than those who had not. In contrast, patients who tested positive for anti-HEV IgG had more elevated levels of total bilirubin than those who tested negative. Conclusions HEV seroprevalence and incidence in patients with clinical hepatitis were relatively high in the Thai population, including the pregnancy and organ transplant subgroups. The results potentially benefit the clinicians in decision-making to investigate HEV antibodies and facilitating proper management for patients.
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Affiliation(s)
- Atiporn Boonyai
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Anchalee Thongput
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Thidarat Sisaeng
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Parisut Phumchan
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Navin Horthongkham
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Wannee Kantakamalakul
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Chutikarn Chaimayo
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
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Walker CM. Adaptive Immune Responses in Hepatitis A Virus and Hepatitis E Virus Infections. Cold Spring Harb Perspect Med 2019; 9:cshperspect.a033472. [PMID: 29844218 DOI: 10.1101/cshperspect.a033472] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Both hepatitis A virus (HAV) and hepatitis E virus (HEV) cause self-limited infections in humans that are preventable by vaccination. Progress in characterizing adaptive immune responses against these enteric hepatitis viruses, and how they contribute to resolution of infection or liver injury, has therefore remained largely frozen for the past two decades. How HAV and HEV infections are so effectively controlled by B- and T-cell immunity, and why they do not have the same propensity to persist as HBV and HCV infections, cannot yet be adequately explained. The objective of this review is to summarize our understanding of the relationship between patterns of virus replication, adaptive immune responses, and acute liver injury in HAV and HEV infections. Gaps in knowledge, and recent studies that challenge long-held concepts of how antibodies and T cells contribute to control and pathogenesis of HAV and HEV infections, are highlighted.
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Affiliation(s)
- Christopher M Walker
- Center for Vaccines and Immunity, The Research Institute at Nationwide Children's, Columbus, Ohio 43004
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5
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Luciani L, Deharo P, Aherfi S, Chalvignac V, Borentain P, Colson P. Hepatitis E virus infection in heart transplant recipients, Southeastern France. Clin Res Hepatol Gastroenterol 2019; 43:108-111. [PMID: 30497845 DOI: 10.1016/j.clinre.2018.09.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Revised: 08/28/2018] [Accepted: 09/15/2018] [Indexed: 02/04/2023]
Affiliation(s)
- Léa Luciani
- Aix-Marseille université, institut de recherche pour le développement (IRD), Assistance publique - hôpitaux de Marseille (AP-HM), microbes, evolution, phylogeny and infection (MEΦI), institut hospitalo-universitaire (IHU) - Méditerranée Infection, 19-21, boulevard Jean-Moulin, 13005 Marseille, France
| | - Pierre Deharo
- Assistance publique - hôpitaux de Marseille (AP-HM), centre hospitalo-universitaire Timone, service de cardiologie, 264, rue Saint-Pierre, 13385 Marseille cedex 05, France
| | - Sarah Aherfi
- Aix-Marseille université, institut de recherche pour le développement (IRD), Assistance publique - hôpitaux de Marseille (AP-HM), microbes, evolution, phylogeny and infection (MEΦI), institut hospitalo-universitaire (IHU) - Méditerranée Infection, 19-21, boulevard Jean-Moulin, 13005 Marseille, France
| | - Virginie Chalvignac
- Assistance publique - hôpitaux de Marseille (AP-HM), centre hospitalo-universitaire Timone, service de chirurgie cardio-thoracique, 264, rue Saint-Pierre, 13385 Marseille cedex 05, France
| | - Patrick Borentain
- Assistance publique - hôpitaux de Marseille (AP-HM), centre hospitalo-universitaire Timone, service d'hépatologie-gastrologie-entérologie, 264, rue Saint-Pierre, 13385 Marseille cedex 05, France
| | - Philippe Colson
- Aix-Marseille université, institut de recherche pour le développement (IRD), Assistance publique - hôpitaux de Marseille (AP-HM), microbes, evolution, phylogeny and infection (MEΦI), institut hospitalo-universitaire (IHU) - Méditerranée Infection, 19-21, boulevard Jean-Moulin, 13005 Marseille, France.
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Pourbaix A, Ouali N, Soussan P, Roque Afonso AM, Péraldi MN, Rondeau E, Peltier J. Evidence of hepatitis E virus transmission by renal graft. Transpl Infect Dis 2017; 19. [PMID: 27775205 DOI: 10.1111/tid.12624] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Revised: 04/26/2016] [Accepted: 09/09/2016] [Indexed: 01/20/2023]
Abstract
Hepatitis E virus (HEV) can cause chronic infection among immunocompromised patients, especially solid organ transplant recipients, and can evolve to cirrhosis. Several modes of transmission are known. Here we describe the first two cases, to our knowledge, of HEV infection transmitted by a kidney graft from the same infected donor that led to chronic hepatitis. Consequently, systematic screening of donors by HEV serology and HEV RNA detection by polymerase chain reaction, particularly in endemic regions, should be considered.
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Affiliation(s)
- Annabelle Pourbaix
- Department of Renal ICU and Kidney Transplantation, Tenon Hospital, Paris, France
| | - Nacera Ouali
- Department of Renal ICU and Kidney Transplantation, Tenon Hospital, Paris, France
| | | | | | | | - Eric Rondeau
- Department of Renal ICU and Kidney Transplantation, Tenon Hospital, Paris, France
| | - Julie Peltier
- Department of Renal ICU and Kidney Transplantation, Tenon Hospital, Paris, France
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7
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Unzueta A, Valdez R, Chang YHH, Desmarteau YM, Heilman RL, Scott RL, Douglas DD, Rakela J. Hepatitis E virus serum antibodies and RNA prevalence in patients evaluated for heart and kidney transplantation. Ann Hepatol 2016; 15:33-40. [PMID: 26626638 DOI: 10.5604/16652681.1184202] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Acute hepatitis E virus (HEV) infection in solid organ transplant recipients is rare, but can cause severe hepatic and extrahepatic complications. We sought to identify the pretransplant prevalence of HEV infection in heart and kidney candidates and any associated risk factors for infection. MATERIAL AND METHODS Stored frozen serum from patients undergoing evaluation for transplant was tested for HEV immunoglobulin G (IgG) antibodies and HEV RNA. All patients were seen at Mayo Clinic Hospital, Phoenix, Arizona, with 333 patients evaluated for heart (n = 132) or kidney (n = 201) transplant. HEV IgG antibodies (anti-HEV IgG) were measured by enzyme-linked immunosorbent assay, and HEV RNA by a noncommercial nucleic acid amplification assay. RESULTS The prevalence of anti-HEV IgG was 11.4% (15/132) for heart transplant candidates and 8.5% (17/201) for kidney transplant candidates, with an overall seroprevalence of 9.6% (32/333). None of the patients tested positive for HEV RNA in the serum. On multivariable analysis, age older than 60 years was associated with HEV infection (adjusted odds ratio, 3.34; 95% CI, 1.54-7.24; P = 0.002). CONCLUSIONS We conclude that there was no evidence of acute HEV infection in this pretransplant population and that older age seems to be associated with positive anti-HEV IgG.
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Fierro NA, Realpe M, Meraz-Medina T, Roman S, Panduro A. Hepatitis E virus: An ancient hidden enemy in Latin America. World J Gastroenterol 2016; 22:2271-2283. [PMID: 26900289 PMCID: PMC4735001 DOI: 10.3748/wjg.v22.i7.2271] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Revised: 10/21/2015] [Accepted: 12/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) infection is a common cause of acute clinical hepatitis worldwide. HEV is an RNA-containing virus and the only member of the genus Hepevirus in the family Hepeviridae. Human HEV is classified into four genotypes widely distributed across the world. The virus is mainly transmitted via the fecal-oral route, and water-borne epidemics have become characteristic of hepatitis E in developing countries, including those in Latin America. The zoonotic potential of HEV is broadly recognized. Thus, there is an urgent need to re-evaluate virus transmission scenarios and to enforce epidemiological surveillance systems. Additionally, it is known that HEV infections, initially defined as self-limiting, can also take chronic courses in immunocompromised patients. Moreover, we recently reported a high seroprevalence of HEV in samples from cirrhotic patients with no other etiological agents present, suggesting the potential role of HEV in the development of chronic liver illness. In this review, HEV genomic variability, transmission, chronic infectious course, zoonotic potential and treatment are discussed. Focus is placed on the impact of HEV infection in Latin America, to support the development of specific control strategies and the handling of this important and typically imperceptible viral infection.
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Aggarwal A, Perumpail RB, Tummala S, Ahmed A. Hepatitis E virus infection in the liver transplant recipients: Clinical presentation and management. World J Hepatol 2016; 8:117-122. [PMID: 26807207 PMCID: PMC4716527 DOI: 10.4254/wjh.v8.i2.117] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Revised: 12/19/2015] [Accepted: 01/07/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) is an emerging pathogen and an increasingly recognized cause of graft hepatitis, especially in the post-orthotopic liver transplantation immunocompromised population. The exact incidence and prevalence of HEV infection in this population remains unclear but is certainly greater than historical estimates. Identifying acute HEV infection in this population is imperative for choosing the right course of management as it is very difficult to distinguish histologically from acute rejection on liver biopsy. Current suggested approach to manage acute HEV involves modifying immunosuppression, especially discontinuing calcineurin inhibitors which are the preferred immunosuppressive agents post-orthotopic liver transplantation. The addition of ribavirin monotherapy has shown promising success rates in clearing HEV infection and is used commonly in reported cases.
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10
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Sue PK, Pisanic N, Heaney CD, Forman M, Valsamakis A, Jackson AM, Ticehurst JR, Montgomery RA, Schwarz KB, Nelson KE, Karnsakul W. Hepatitis E Virus Infection Among Solid Organ Transplant Recipients at a North American Transplant Center. Open Forum Infect Dis 2016; 3:ofw006. [PMID: 27014710 PMCID: PMC4804338 DOI: 10.1093/ofid/ofw006] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Accepted: 01/12/2016] [Indexed: 02/07/2023] Open
Abstract
Background. Autochthonous hepatitis E virus (HEV) infection has been reported in over 200 solid organ transplant (SOT) recipients since 2006, yet little is known about the burden of HEV among SOT recipients in North America. We performed a retrospective, cross-sectional study to investigate the prevalence and risk factors associated with HEV infection among SOT recipients at our institution. Methods. Children and adults (n = 311) who received allografts between 1988 and 2012 at the Johns Hopkins Hospital were assessed for evidence of HEV infection by testing posttransplantation serum samples for HEV antibody by enzyme immunoassay and HEV RNA by reverse transcription quantitative polymerase chain reaction. Individuals with evidence of posttransplant HEV infection (presence of anti-HEV immunoglobulin [Ig]M antibody, anti-HEV IgG seroconversion, or HEV RNA) were compared with individuals without evidence of infection and assessed for risk factors associated with infection. Results. Twelve individuals (4%) developed posttransplant HEV infection. Posttransplant HEV infection was associated with an increased risk for graft rejection (odds ratio, 14.2; P = .03). No individuals developed chronic infection. Conclusions. Solid organ transplant recipients in the United States are at risk for posttransplant HEV infection. Further studies are needed to characterize environmental risk factors and the risk of HEV infection after SOT in North America.
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Affiliation(s)
- Paul K Sue
- Department of Pediatrics, Division of Pediatric Infectious Diseases, The Johns Hopkins University School of Medicine,; Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Nora Pisanic
- Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health
| | - Christopher D Heaney
- Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health,; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health
| | - Michael Forman
- Department of Pathology, Division of Medical Microbiology
| | | | | | - John R Ticehurst
- Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health,; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health
| | | | - Kathleen B Schwarz
- Department of Pediatrics, Division of Pediatric Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; and
| | - Kenrad E Nelson
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health
| | - Wikrom Karnsakul
- Department of Pediatrics, Division of Pediatric Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; and
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Lapa D, Capobianchi MR, Garbuglia AR. Epidemiology of Hepatitis E Virus in European Countries. Int J Mol Sci 2015; 16:25711-43. [PMID: 26516843 PMCID: PMC4632823 DOI: 10.3390/ijms161025711] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Revised: 09/12/2015] [Accepted: 10/16/2015] [Indexed: 12/22/2022] Open
Abstract
Over the last decade the seroprevalence of immunoglobulin (IgG) anti hepatitis E virus (HEV) has been increasing in European countries and shows significant variability among different geographical areas. In this review, we describe the serological data concerning the general population and risk groups in different European countries. Anti-HEV antibody prevalence ranged from 1.3% (blood donors in Italy) to 52% (blood donors in France). Various studies performed on risk groups in Denmark, Moldova and Sweden revealed that swine farmers have a high seroprevalence of HEV IgG (range 13%-51.1%), confirming that pigs represent an important risk factor in HEV infection in humans. Subtypes 3e,f are the main genotypes detected in the European population. Sporadic cases of autochthonous genotype 4 have been described in Spain, France, and Italy. Although most HEV infections are subclinical, in immune-suppressed and transplant patients they could provoke chronic infection. Fulminant hepatitis has rarely been observed and it was related to genotype 3. Interferon and ribavirin treatment was seen to represent the most promising therapy.
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Affiliation(s)
- Daniele Lapa
- Laboratory of Virology, "Lazzaro Spallanzani" National Institute for Infectious Diseases, Via Portuense 292, Rome 00149, Italy.
| | - Maria Rosaria Capobianchi
- Laboratory of Virology, "Lazzaro Spallanzani" National Institute for Infectious Diseases, Via Portuense 292, Rome 00149, Italy.
| | - Anna Rosa Garbuglia
- Laboratory of Virology, "Lazzaro Spallanzani" National Institute for Infectious Diseases, Via Portuense 292, Rome 00149, Italy.
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12
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Systematic serological testing for hepatitis E virus in kidney transplant recipients. J Clin Microbiol 2015; 53:1523-30. [PMID: 25694530 DOI: 10.1128/jcm.03624-14] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2014] [Accepted: 02/11/2015] [Indexed: 12/24/2022] Open
Abstract
Hepatitis E virus (HEV) genotype 3 is endemic in Europe and hyperendemic in southern France. Recent reports of a high prevalence of HEV RNA in blood donations and in culinary specialties from this geographical area confirmed the endemicity of HEV and sources of viral transmission in this geographical area. HEV causes acute and chronic hepatitis in solid organ transplant recipients. Since March 2012, we have implemented systematic HEV serological testing in our cohort of kidney transplant recipients (KTRs) in Marseille in southeastern France. The aim of our study was to assess HEV exposure in this cohort between March 2012 and May 2014. During these 27 months, we found that 39% of the patients who underwent kidney transplantation had an anti-HEV IgG response using a sensitive microplate enzyme immunoassay. This seroprevalence was approximately 43% at both 1 and 8 years after, using the same assay. In addition, systematic HEV serological testing detected 6 cases of HEV infection among 578 KTRs (1%) during the 27 months of the study, with 5 at an acute stage and 1 at a chronic stage. In conclusion, continuous HEV monitoring in this population is useful for better understanding the epidemiology of HEV in France, because these patients are a well-monitored population. Moreover, HEV monitoring in KTRs is clinically relevant because HEV represents a clinical threat in these patients. Nevertheless, HEV serological testing may be more fruitful for identifying HEV infections when performed in cases of biological liver abnormalities than when performed systematically.
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Hepatitis e infection in a renal transplant recipient. Case Rep Nephrol 2014; 2014:865471. [PMID: 25295201 PMCID: PMC4177828 DOI: 10.1155/2014/865471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2014] [Accepted: 07/29/2014] [Indexed: 11/18/2022] Open
Abstract
An asymptomatic 35-year-old renal transplant recipient was noted to have deranged liver function tests. Liver biopsy revealed a portal inflammatory process with mild lobular activity and portal fibrous expansion, consistent with a virally mediated process. An extensive viral screen confirmed infection with Hepatitis E virus genotype 3 (HEV-3). There is increased awareness about locally acquired Hepatitis E virus (HEV) infection in the transplant population in the UK. The important implications of this infection are becoming more apparent as progression to liver cirrhosis can occur. However, the incidence, natural history, and treatment of HEV infection in the transplant population are not well established. This report illustrates a case of delayed spontaneous clearance of the HEV infection.
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Abstract
Hepatitis E virus (HEV) infection is a worldwide disease. An improved understanding of the natural history of HEV infection has been achieved within the last decade. Several reservoirs and transmission modes have been identified. Hepatitis E is an underdiagnosed disease, in part due to the use of serological assays with low sensitivity. However, diagnostic tools, including nucleic acid-based tests, have been improved. The epidemiology and clinical features of hepatitis E differ between developing and developed countries. HEV infection is usually an acute self-limiting disease, but in developed countries it causes chronic infection with rapidly progressive cirrhosis in organ transplant recipients, patients with hematological malignancy requiring chemotherapy, and individuals with HIV. HEV also causes extrahepatic manifestations, including a number of neurological syndromes and renal injury. Acute infection usually requires no treatment, but chronic infection should be treated by reducing immunosuppression in transplant patients and/or the use of antiviral therapy. In this comprehensive review, we summarize the current knowledge about the virus itself, as well as the epidemiology, diagnostics, natural history, and management of HEV infection in developing and developed countries.
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