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Baymakova MP, Konaktchieva M, Kunchev M, Popivanov G, Kundurzhiev T, Tsachev I, Mutafchiyski V. First Insight into the Seroprevalence of Hepatitis E Virus and Associated Risk Factors Among Liver Transplant Recipients from Bulgaria. Vector Borne Zoonotic Dis 2025. [PMID: 39943906 DOI: 10.1089/vbz.2024.0101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/19/2025] Open
Abstract
Introduction: Hepatitis E virus (HEV) infection is caused by viruses belonging to the Hepeviridae family. HEV infection can be self-limiting; however, extrahepatic manifestations may be present. The purpose of the current study was to establish the seroprevalence of HEV among Bulgarian liver transplant recipients (LTRs) and to identify associated risk factors. Materials & Methods: The present study was conducted between April 1, 2023, and October 30, 2023, at the Military Medical Academy, Sofia, Bulgaria. All serum samples were tested for anti-HEV IgG/IgM using HEV IgG/IgM enzyme-linked immunosorbent assay on Dia.Pro (Milan, Italy). Each participating LTR completed a detailed paper-based closed-ended questionnaire regarding the associated risk factors for HEV infection. Results: The study included 73 LTRs with a mean age of 47.0 ± 14.0 years. Anti-HEV IgG antibodies were detected in 25 LTRs (34.2%), including 20 males (37.7%) and 5 females (25%). All participants were HEV-IgM negative. HEV seropositivity rates were higher but not statistically significant in LTRs aged >60 years than in those aged <60 years (40% vs. 32.7%). A significant factor by logistic regression was "high level of education" (odds ratio [OR] = 2.917; p = 0.038). Conclusion: To the best of our knowledge, this is the first seroepidemiological HEV study among LTRs from Bulgaria that found a high seroprevalence (34.2%).
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Affiliation(s)
| | - Marina Konaktchieva
- Department of Gastroenterology and Hepatology, Military Medical Academy, Sofia, Bulgaria
| | - Metodi Kunchev
- Department of Virology, Military Medical Academy, Sofia, Bulgaria
| | - Georgi Popivanov
- Department of Surgery, Military Medical Academy, Sofia, Bulgaria
| | - Todor Kundurzhiev
- Department of Occupational Medicine, Faculty of Public Health, Medical University, Sofia, Bulgaria
| | - Ilia Tsachev
- Department of Microbiology, Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, Trakia University, Stara Zagora, Bulgaria
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He P, Li J, Wang C, Zhang J, Jiang Y, Liu H, Zhao Y, Li Z, Gao Y, Wang Y. Incidence and risk factors of de novo hepatitis E virus infection after receiving liver transplantation. J Med Virol 2024; 96:e29939. [PMID: 39360633 DOI: 10.1002/jmv.29939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 09/07/2024] [Accepted: 09/17/2024] [Indexed: 10/04/2024]
Abstract
Organ transplant recipients with hepatitis E virus (HEV) infection bears high risk to develop chronic hepatitis, which is generally associated with immunosuppressive therapies. This study aimed to identify the incidence and predictors of de novo HEV infection in patients after receiving transplantation. We performed a large retrospective study to investigate the prevalence of anti-HEV at baseline, incidence of de novo HEV infection after transplantation, and the risk factors of HEV infection among patients with liver transplant in China. A total of 407 liver transplant recipients were examined for the presence of anti-HEV immunoglobulin G, IgM antibodies, and HEV RNA in serum. Basal indexes in individuals with evidence of post-transplant HEV infection were compared with those without evidence of that, and risk factors associated with HEV infection were assessed. The prevalence of anti-HEV at pretransplant in liver transplant recipients was 25.8% (105/407). Serum-negative conversion occurred in 34 (32.38%) of 105 liver transplant patients. Sixty-five out of 302 patients had de novo HEV infection after transplantation, with a cumulative incidence of 42.74% during follow-up. After transplantation, HEV infection was associated with liver failure (p = 0.012), hypoproteinemia (p = 0.030) and higher level of r-glutamyl transferase (GGT) (p = 0.022) before transplantation. Graft rejection (OR = 0.075; p = 0.045) was negatively associated with serum-negative conversion in patients who had positive anti-HEV antibody before transplantation. The incidence of de novo HEV infection after transplantation were higher in China. Liver failure, hypoproteinemia, and GGT elevation may be associated with HEV infection after liver transplantation. This study suggests that prevention and control of HEV infection after liver transplantation should be paid attention in patients bearing these risk factors.
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Affiliation(s)
- Ping He
- Department of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen, China
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Jialei Li
- Medical School of Nanjing University, Nanjing, China
| | - Chen Wang
- Department of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen, China
| | - Jiayue Zhang
- School of Pharmacy, Jiangsu Food & Pharmaceutical Science College, Huaian, China
| | - Yiyun Jiang
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Hongyang Liu
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Yao Zhao
- Department of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen, China
| | - Zhiwei Li
- Department of Hepato-Biliary Surgery, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Yinjie Gao
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Yijin Wang
- Department of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen, China
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Orosz L, Sárvári KP, Dernovics Á, Rosztóczy A, Megyeri K. Pathogenesis and clinical features of severe hepatitis E virus infection. World J Virol 2024; 13:91580. [PMID: 38984076 PMCID: PMC11229844 DOI: 10.5501/wjv.v13.i2.91580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 02/08/2024] [Accepted: 04/15/2024] [Indexed: 06/24/2024] Open
Abstract
The hepatitis E virus (HEV), a member of the Hepeviridae family, is a small, non-enveloped icosahedral virus divided into eight distinct genotypes (HEV-1 to HEV-8). Only genotypes 1 to 4 are known to cause diseases in humans. Genotypes 1 and 2 commonly spread via fecal-oral transmission, often through the consumption of contaminated water. Genotypes 3 and 4 are known to infect pigs, deer, and wild boars, often transferring to humans through inadequately cooked meat. Acute hepatitis caused by HEV in healthy individuals is mostly asymptomatic or associated with minor symptoms, such as jaundice. However, in immunosuppressed individuals, the disease can progress to chronic hepatitis and even escalate to cirrhosis. For pregnant women, an HEV infection can cause fulminant liver failure, with a potential mortality rate of 25%. Mortality rates also rise amongst cirrhotic patients when they contract an acute HEV infection, which can even trigger acute-on-chronic liver failure if layered onto pre-existing chronic liver disease. As the prevalence of HEV infection continues to rise worldwide, highlighting the particular risks associated with severe HEV infection is of major medical interest. This text offers a brief summary of the characteristics of hepatitis developed by patient groups at an elevated risk of severe HEV infection.
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Affiliation(s)
- László Orosz
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
| | - Károly Péter Sárvári
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
| | - Áron Dernovics
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
| | - András Rosztóczy
- Department of Internal Medicine, Division of Gastroenterology, University of Szeged, Szeged 6725, Csongrád-Csanád, Hungary
| | - Klára Megyeri
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
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Zicker M, Pinho JRR, Welter EAR, Guardia BD, da Silva PGTM, da Silveira LB, Camargo LFA. The Risk of Reinfection or Primary Hepatitis E Virus Infection at a Liver Transplant Center in Brazil: An Observational Cohort Study. Viruses 2024; 16:301. [PMID: 38400077 PMCID: PMC10893537 DOI: 10.3390/v16020301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 01/31/2024] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
The hepatitis E virus is a major etiological agent of chronic hepatitis in immunosuppressed individuals. Seroprevalence in the liver transplantation setting varies according to the seroprevalence of the general population in different countries. This was a prospective cohort study of liver transplant recipients in southeastern Brazil. Recipients were systematically followed for one year, with the objective of determining the prevalence, incidence, and natural history of HEV infection in this population. We included 107 liver transplant recipients and 83 deceased donors. Positivity for anti-HEV IgG was detected in 10.2% of the recipients and in 9.7% of the donors. None of the patients tested positive for HEV RNA at baseline or during follow-up. There were no episodes of reactivation or seroconversion, even in cases of serological donor-recipient mismatch or in recipients with acute hepatitis. Acute and chronic HEV infections seem to be rare events in the region studied. That could be attributable to social, economic, and environmental factors. Our data indicate that, among liver transplant recipients, hepatitis E should be investigated only when there are elevated levels of transaminases with no defined cause, as part of the differential diagnosis of seronegative hepatitis after transplantation.
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Affiliation(s)
- Michelle Zicker
- Division of Infectious Diseases, Department of Internal Medicine, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil;
| | - João R. R. Pinho
- Research and Development Sector, Clinical Laboratory, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | - Eliane A. R. Welter
- Research and Development Sector, Clinical Laboratory, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | - Bianca D. Guardia
- Liver Transplant Program, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | | | | | - Luís F. A. Camargo
- Division of Infectious Diseases, Department of Internal Medicine, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil;
- Faculdade Israelita de Ciências da Saúde Albert Einstein, São Paulo 05653-120, Brazil
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Zahmanova G, Takova K, Tonova V, Koynarski T, Lukov LL, Minkov I, Pishmisheva M, Kotsev S, Tsachev I, Baymakova M, Andonov AP. The Re-Emergence of Hepatitis E Virus in Europe and Vaccine Development. Viruses 2023; 15:1558. [PMID: 37515244 PMCID: PMC10383931 DOI: 10.3390/v15071558] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/11/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. Transmission of HEV mainly occurs via the fecal-oral route (ingesting contaminated water or food) or by contact with infected animals and their raw meat products. Some animals, such as pigs, wild boars, sheep, goats, rabbits, camels, rats, etc., are natural reservoirs of HEV, which places people in close contact with them at increased risk of HEV disease. Although hepatitis E is a self-limiting infection, it could also lead to severe illness, particularly among pregnant women, or chronic infection in immunocompromised people. A growing number of studies point out that HEV can be classified as a re-emerging virus in developed countries. Preventative efforts are needed to reduce the incidence of acute and chronic hepatitis E in non-endemic and endemic countries. There is a recombinant HEV vaccine, but it is approved for use and commercially available only in China and Pakistan. However, further studies are needed to demonstrate the necessity of applying a preventive vaccine and to create conditions for reducing the spread of HEV. This review emphasizes the hepatitis E virus and its importance for public health in Europe, the methods of virus transmission and treatment, and summarizes the latest studies on HEV vaccine development.
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Affiliation(s)
- Gergana Zahmanova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
- Department of Technology Transfer and IP Management, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria
| | - Katerina Takova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
| | - Valeria Tonova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
| | - Tsvetoslav Koynarski
- Department of Animal Genetics, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Laura L Lukov
- Faculty of Sciences, Brigham Young University-Hawaii, Laie, HI 96762, USA
| | - Ivan Minkov
- Department of Technology Transfer and IP Management, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria
- Institute of Molecular Biology and Biotechnologies, 4108 Markovo, Bulgaria
| | - Maria Pishmisheva
- Department of Infectious Diseases, Pazardzhik Multiprofile Hospital for Active Treatment, 4400 Pazardzhik, Bulgaria
| | - Stanislav Kotsev
- Department of Infectious Diseases, Pazardzhik Multiprofile Hospital for Active Treatment, 4400 Pazardzhik, Bulgaria
| | - Ilia Tsachev
- Department of Microbiology, Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Magdalena Baymakova
- Department of Infectious Diseases, Military Medical Academy, 1606 Sofia, Bulgaria
| | - Anton P Andonov
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
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Zhang J, Zheng Z, Xia N. Prophylactic Hepatitis E Vaccine. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:227-245. [PMID: 37223870 DOI: 10.1007/978-981-99-1304-6_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
The hepatitis E has been increasingly recognized as an underestimated global disease burden in recent years. Subpopulations with more serious infection associated damage or death include pregnant women, patients with basic liver diseases, and elderly persons. Vaccine would be the most effective means for prevention of HEV infection. The lack of an efficient cell culture system for HEV makes the development of classic inactive or attenuated vaccine infeasible. Hence, the recombinant vaccine approaches are explored deeply. The neutralizing sites are located almost exclusively in the capsid protein, pORF2, of the virion. Based on pORF2, many vaccine candidates showed potential of protecting primate animals, two of them were tested in human and evidenced to be well-tolerated in adults and highly efficacious in preventing hepatitis E. The world's first hepatitis E vaccine, Hecolin® (HEV 239 vaccine), was licensed in China and launched in 2012.
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Affiliation(s)
- Jun Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, 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, Xiamen University, 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, Xiamen University, Xiamen, China
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Zhao C, Wang Y. Laboratory Diagnosis of HEV Infection. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:199-213. [PMID: 37223868 DOI: 10.1007/978-981-99-1304-6_14] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Serological and nucleic acid tests for detecting hepatitis E virus (HEV) have been developed for both epidemiologic and diagnostic purposes. The laboratory diagnosis of HEV infection depends on the detection of HEV antigen or HEV RNA in the blood, stool, and other body fluids, and serum antibodies against HEV (immunoglobulin [Ig]A, IgM, and IgG). Anti-HEV IgM antibodies and low avidity IgG can be detected during the acute phase of the illness and can last approximately 12 months, representing primary infection, whereas anti-HEV IgG antibodies can last more than several years, representing remote exposure. Thus, the diagnosis of acute infection is based on the presence of anti-HEV IgM, low avidity IgG, HEV antigen, and HEV RNA, while epidemiological investigations are mainly based on anti-HEV IgG. Although significant progress has been made in developing and optimizing different formats of HEV assays, improving their sensitivity and specificity, there are many shortcomings and challenges in inter-assay concordance, validation, and standardization. This article reviews the current knowledge on the diagnosis of HEV infection, including the most common available laboratory diagnostic techniques.
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Affiliation(s)
- Chenyan Zhao
- Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing, China
| | - Youchun Wang
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, China.
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Hepatitis E Virus Infection, a Risk for Liver Transplant Recipients in Sweden. Transplant Direct 2022; 8:e1409. [PMID: 36398195 PMCID: PMC9666183 DOI: 10.1097/txd.0000000000001409] [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: 08/15/2022] [Revised: 09/08/2022] [Accepted: 09/20/2022] [Indexed: 11/16/2022] Open
Abstract
Following exposure to hepatitis E virus (HEV), liver transplant (LT) recipients have an increased risk of developing chronic infection, which may rapidly progress to severe liver damage if not treated. The prevalence of HEV infection after LT is unclear and likely varies geographically. The aim of this study was to investigate the prevalence of acute and chronic HEV infection among LT recipients in an HEV endemic region.
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Markakis GE, Papatheodoridis GV, Cholongitas E. Epidemiology and treatment of hepatitis E in the liver transplantation setting: A literature review. J Viral Hepat 2022; 29:698-718. [PMID: 35644040 DOI: 10.1111/jvh.13709] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 02/01/2022] [Accepted: 05/10/2022] [Indexed: 12/09/2022]
Abstract
Hepatitis E virus (HEV) is a common cause of acute hepatitis in developing countries, but it can also take a chronic course especially in immunocompromised patients. Its epidemiology after liver transplantation (LT) is hard to assess and treatment options are still explored. Between 2009 and 2020, literature reporting HEV prevalence and treatment in LT recipients was searched and a synthesis was attempted. Sixteen studies reported HEV prevalence in consecutive LT patients: HEV RNA positivity ranged between 0%-1.4% and 0%-7.7% for Western and Eastern cohorts, respectively. In studies published between 2009-2014 and 2015-2020, HEV RNA positivity ranged between 0.35%-1.3% (all European) and 0%-7.7% (European: 0%-1.4%), respectively. Five studies evaluated HEV prevalence in LT recipients with abnormal liver enzymes: HEV RNA positivity was 2.9% in studies published between 2009 and 2014 and from 3.5% to 20% in studies published between 2015 and 2020. Twenty-seven studies reported HEV treatment in LT recipients: sustained virologic response was achieved in 15% by immunosuppression reduction alone and in 83% of cases by ribavirin regiments. Chronic HEV infection is affecting LT recipients, mostly those with abnormal liver enzymes and in Eastern countries. HEV diagnoses should be based on PCR techniques. Successful treatment can be achieved with ribavirin in most cases.
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Affiliation(s)
- George E Markakis
- Department of Gastroenterology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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Ghandili S, Lindhauer C, Pischke S, zur Wiesch JS, von Kroge PH, Polywka S, Bokemeyer C, Fiedler W, Kröger N, Ayuk F, Adjallé R, Modemann F. Clinical features of hepatitis E infections in patients with hematologic disorders. Haematologica 2022; 107:2870-2883. [PMID: 35770534 PMCID: PMC9713558 DOI: 10.3324/haematol.2022.280853] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Indexed: 12/14/2022] Open
Abstract
Hepatitis E virus is increasingly being reported to cause chronic infection in immunocompromised patients. However, less is known about patients with an underlying hematologic disease. In particular, the impact of hepatitis E infection on oncological therapy has been poorly described. In this retrospective single-center study, we analyzed 35 hematologic patients with hepatitis E, including 20 patients under active oncological treatment and 15 patients who were in the posttreatment follow-up or under active surveillance. The primary aim was to describe the clinical courses with particular focus on any hepatitis E-related therapy modifications of cancer-directed therapy. In the majority (60%) of patients who were under active oncological treatment, hepatitis E-related therapy modifications were made, and 25% of deaths were due to progression of the hematologic disease. In patients receiving concomitant oncological treatment, no hepatitis Erelated deaths occurred. In contrast, two patients in the follow-up group died from hepatitis E-associated acute-onchronic liver failure. Chronic hepatitis E was observed in 34% of all cases and 43% received ribavirin therapy; of those, 27% achieved a sustained virological response. CD20-directed therapy was the only independent risk factor for developing chronic hepatitis E. We conclude that CD20-directed treatment at any time point is a risk factor for developing chronic hepatitis E. Nevertheless, since mortality from the progression of hematologic disease was higher than hepatitis E-related mortality, we suggest careful case-by-case decisions on modifications of cancer treatment. Patients in the posttreatment follow-up phase may also suffer from severe courses and hepatitis E chronicity occurs as frequently as in patients undergoing active therapy.
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Affiliation(s)
- Susanne Ghandili
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf,*SG and CL contributed equally as co-first authors
| | - Cecilia Lindhauer
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf,*SG and CL contributed equally as co-first authors
| | - Sven Pischke
- The I. Department of Internal Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf
| | - Julian Schulze zur Wiesch
- The I. Department of Internal Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf
| | - Philipp H. von Kroge
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf
| | - Susanne Polywka
- The Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf
| | - Carsten Bokemeyer
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf
| | - Walter Fiedler
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf
| | - Nicolaus Kröger
- Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf and
| | - Francis Ayuk
- Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf and
| | - Raissa Adjallé
- Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf and ,RA and FM contributed equally as co-last authors
| | - Franziska Modemann
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf,Mildred Scheel Cancer Career Center, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany,RA and FM contributed equally as co-last authors
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Damiris K, Aghaie Meybodi M, Niazi M, Pyrsopoulos N. Hepatitis E in immunocompromised individuals. World J Hepatol 2022; 14:482-494. [PMID: 35582299 PMCID: PMC9055194 DOI: 10.4254/wjh.v14.i3.482] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/15/2021] [Accepted: 02/13/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) originally identified as a cause of acute icteric hepatitis in developing countries has grown to be a cause of zoonotic viral hepatitis in developed countries such as the United States. While there are eight identified genotypes to date, genotype 1 (HEV1), HEV2, HEV3, HEV4 are the most common to infect humans. HEV1 and HEV2 are most common in developing countries including Latina America, Africa and Asia, and are commonly transmitted through contaminated water supplies leading to regional outbreaks. In contrast HEV3 and HEV4 circulate freely in many mammalian animals and can lead to occasional transmission to humans through fecal contamination or consumption of undercooked meat. The incidence and prevalence of HEV in the United States is undetermined given the absence of FDA approved serological assays and the lack of commercially available testing. In majority of cases, HEV infection is a self-limiting hepatitis requiring only symptomatic treatment. However, this is not the case in immunocompromised individuals, including those that have undergone solid organ or stem cell transplantation. In this subset of patients, chronic infection can be life threatening as hepatic insult can lead to inflammation and fibrosis with subsequent cirrhosis and death. The need for re-transplantation as a result of post-transplant hepatitis is of great concern. In addition, there have been many reported incidents of extrahepatic manifestations, for which the exact mechanisms remain to be elucidated. The cornerstone of treatment in immunocompromised solid organ transplant recipients is reduction of immunosuppressive therapies, while attempting to minimize the risk of organ rejection. Subsequent treatment options include ribavirin, and pegylated interferon alpha in those who have demonstrated ribavirin resistance. Further investigation assessing safety and efficacy of anti-viral therapy is imperative given the rising global health burden. Given this concern, vaccination has been approved in China with other investigations underway throughout the world. In this review we introduce the epidemiology, diagnosis, clinical manifestations, and treatment of HEV, with emphasis on immunocompromised individuals in the United States.
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Affiliation(s)
- Konstantinos Damiris
- Department of Medicine, Rutgers - New Jersey Medical School, Newark, NJ 07103, United States
| | - Mohamad Aghaie Meybodi
- Department of Medicine, Rutgers - New Jersey Medical School, Newark, NJ 07103, United States
| | - Mumtaz Niazi
- Department of Medicine - Gastroenterology and Hepatology, Rutgers - New Jersey Medical School, Newark, NJ 07103, United States
| | - Nikolaos Pyrsopoulos
- Department of Medicine - Gastroenterology and Hepatology, Rutgers - New Jersey Medical School, Newark, NJ 07103, United States
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Fantilli A, López Villa SD, Zerega A, Di Cola G, López L, Wassaf Martínez M, Pisano MB, Ré VE. Hepatitis E virus infection in a patient with alcohol related chronic liver disease: a case report of acute-on-chronic liver failure. Virol J 2021; 18:245. [PMID: 34886883 PMCID: PMC8662871 DOI: 10.1186/s12985-021-01714-w] [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: 07/30/2021] [Accepted: 11/26/2021] [Indexed: 02/07/2023] Open
Abstract
Background The hepatitis E virus (HEV) infection has been described as a causing factor for acute-on-chronic-liver-failure (ACLF) in patients with underlying chronic liver disease (CLD), such as chronic hepatitis or cirrhosis, which could end in the failure of one or more organs and high short-term mortality. There are scarce data about the association of HEV in patients with chronic liver disorders in South America. Case presentation A 56-year-old hypertensive male with a history of type 2 diabetes was diagnosed with alcohol-related-liver cirrhosis in February 2019. A year later, the patient was admitted to hospital due to fatigue, jaundice and acholia. No evidence of hepatitis A virus, hepatitis B virus, hepatitis C virus, Epstein–Barr virus, herpes zoster virus and cytomegalovirus infections were found. Nevertheless, in February and March, 2020 the patient was positive for HEV-IgM and HEV-IgG, and HEV genotype 3 RNA was detected in sera. Afterwards, he presented grade I hepatic encephalopathy and, therefore, was diagnosed with acute hepatitis E-on-chronic liver disease. The patient reported a recent travel to the Argentine coast, where he consumed seafood. Besides, he reveled to have consumed pork meat and had no history of blood transfusion. Conclusion This report describes a unique case of hepatitis E virus infection in a patient with alcohol-related cirrhosis. This is the first report of a patient with HEV-related ACLF in Argentina and it invokes the importance of HEV surveillance and treatment among patients with CLD, such as alcohol-related cirrhosis.
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Affiliation(s)
- Anabella Fantilli
- Instituto de Virología "Dr. J. M. Vanella"- InViV- CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016, Córdoba, Argentina.
| | | | | | - Guadalupe Di Cola
- Instituto de Virología "Dr. J. M. Vanella"- InViV- CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016, Córdoba, Argentina
| | - Luis López
- Instituto Modelo de Cardiología, Córdoba, Argentina
| | | | - María Belén Pisano
- Instituto de Virología "Dr. J. M. Vanella"- InViV- CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016, Córdoba, Argentina
| | - Viviana Elizabeth Ré
- Instituto de Virología "Dr. J. M. Vanella"- InViV- CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016, Córdoba, Argentina
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13
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Velavan TP, Pallerla SR, Johne R, Todt D, Steinmann E, Schemmerer M, Wenzel JJ, Hofmann J, Shih JWK, Wedemeyer H, Bock CT. Hepatitis E: An update on One Health and clinical medicine. Liver Int 2021; 41:1462-1473. [PMID: 33960603 DOI: 10.1111/liv.14912] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 03/09/2021] [Accepted: 04/08/2021] [Indexed: 12/12/2022]
Abstract
The hepatitis E virus (HEV) is one of the main causes of acute hepatitis and the de facto global burden is underestimated. HEV-related clinical complications are often undetected and are not considered in the differential diagnosis. Convincing findings from studies suggest that HEV is clinically relevant not only in developing countries but also in industrialized countries. Eight HEV genotypes (HEV-1 to HEV-8) with different human and animal hosts and other HEV-related viruses are in circulation. Transmission routes vary by genotype and location, with large waterborne outbreaks in developing countries and zoonotic food-borne infections in developed countries. An acute infection can be aggravated in pregnant women, organ transplant recipients, patients with pre-existing liver disease and immunosuppressed patients. HEV during pregnancy affects the fetus and newborn with an increased risk of vertical transmission, preterm and stillbirth, neonatal jaundice and miscarriage. Hepatitis E is associated with extrahepatic manifestations that include neurological disorders such as neuralgic amyotrophy, Guillain-Barré syndrome and encephalitis, renal injury and haematological disorders. The risk of transfusion-transmitted HEV is increasingly recognized in Western countries where the risk may be because of a zoonosis. RNA testing of blood components is essential to determine the risk of transfusion-transmitted HEV. There are currently no approved drugs or vaccines for HEV infections. This review focuses on updating the latest developments in zoonoses, screening and diagnostics, drugs in use and under development, and vaccines.
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Affiliation(s)
- Thirumalaisamy P Velavan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.,Vietnamese-German Center for Medical Research, VG-CARE, Hanoi, Vietnam.,Faculty of Medicine, Duy Tan University, Da Nang, Vietnam
| | - Srinivas R Pallerla
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.,Vietnamese-German Center for Medical Research, VG-CARE, Hanoi, Vietnam
| | - Reimar Johne
- German Federal Institute for Risk Assessment, Berlin, Germany
| | - Daniel Todt
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany.,European Virus Bioinformatics Center (EVBC), Jena, Germany
| | - Eike Steinmann
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
| | - Mathias Schemmerer
- Institute of Clinical Microbiology and Hygiene, National Consultant Laboratory for HAV and HEV, University Medical Center Regensburg, Regensburg, Germany
| | - Jürgen J Wenzel
- Institute of Clinical Microbiology and Hygiene, National Consultant Laboratory for HAV and HEV, University Medical Center Regensburg, Regensburg, Germany
| | - Jörg Hofmann
- Institute of Virology, Charité Universitätsmedizin Berlin, Labor Berlin-Charité-Vivantes GmbH, Berlin, Germany
| | | | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infection Research, Partner Hannover-Braunschweig, Braunschweig, Germany
| | - Claus-Thomas Bock
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.,Division of Viral Gastroenteritis and Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
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14
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Fontana RJ, Engle RE, Gottfried M, Hammed B, Hanje J, Durkalski V, Kleiner DE, Nguyen H, Nishimura N, Lee WM, Farci P. Role of Hepatitis E Virus Infection in North American Patients With Severe Acute Liver Injury. Clin Transl Gastroenterol 2020; 11:e00273. [PMID: 33259165 PMCID: PMC7665257 DOI: 10.14309/ctg.0000000000000273] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 10/07/2020] [Indexed: 12/17/2022] Open
Abstract
INTRODUCTION The aim of this study was to determine the role of hepatitis E virus (HEV) infection in a large cohort of prospectively enrolled patients with severe acute liver injury (ALI). METHODS Serum samples from 594 consecutive adults enrolled between 2008 and 2018 in the US Acute Liver Failure Study Group ALI registry were tested for anti-HEV IgM and anti-HEV IgG levels. Those with detectable anti-HEV IgM underwent further testing for HEV RNA using real-time polymerase chain reaction. RESULTS The median age of patients was 38 years; 41% were men and 72% Caucasian. Etiologies of ALI included acetaminophen hepatotoxicity (50%), autoimmune hepatitis (8.9%), hepatitis B virus (8.9%), and idiosyncratic drug-induced liver injury (7.9%). Overall, 62 patients (10.4%) were negative for anti-HEV IgM but positive for IgG, whereas only 3 men (0.5%) were positive for both anti-HEV IgM and IgG. These 3 cases were initially diagnosed as having indeterminate, HEV, and hepatitis B virus-related ALI. One of these patients had detectable HEV RNA genotype 3, and another anti-HEV IgM+ patient had detectable HEV antigens by immunohistochemistry on liver biopsy. On multivariate modeling, older (odds ratio: 1.99) and non-Caucasian subjects (odds ratio: 2.92) were significantly more likely to have detectable anti-HEV IgG (P < 0.0001). DISCUSSION Acute HEV infection is an infrequent cause of ALI in hospitalized North American adults. The anti-HEV IgG+ patients were significantly older and more likely to be non-Caucasian. These data are consistent with other population-based studies that indicate exposure to HEV in the general US population is declining over time and might reflect a cohort effect.
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Affiliation(s)
- Robert J. Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Ronald E. Engle
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - Michelle Gottfried
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Bilal Hammed
- Department of Medicine, UCSF, San Francisco, California, USA
| | - James Hanje
- Department of Medicine, Ohio State University, Columbus, Ohio, USA
| | - Valerie Durkalski
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - David E. Kleiner
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Hanh Nguyen
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - Norihisa Nishimura
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - William M. Lee
- Department of Medicine, University of Texas Southwestern, Dallas, Texas, USA
| | - Patrizia Farci
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
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15
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Thakur V, Ratho RK, Kumar S, Saxena SK, Bora I, Thakur P. Viral Hepatitis E and Chronicity: A Growing Public Health Concern. Front Microbiol 2020; 11:577339. [PMID: 33133046 PMCID: PMC7550462 DOI: 10.3389/fmicb.2020.577339] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 09/03/2020] [Indexed: 12/15/2022] Open
Abstract
Hepatitis E viral infection recently emerges as a global health concern. Over the last decade, the understanding of hepatitis E virus (HEV) had changed with the discovery of new genotypes like genotype-7 and genotype-8 with associated host and mode of infection. Diversification in the mode of hepatitis E infection transmission through blood transfusion, and organ transplants in contrast to classical feco-oral and zoonotic mode is the recent medical concern. The wide spectrum of infection ranging from self-limiting to acute liver failure is now overpowered by HEV genotype-specific chronic infection especially in transplant patients. This concern is further escalated by the extra-hepatic manifestations of HEV targeting the central nervous system (CNS), kidney, heart, and pancreas. However, with the development of advanced efficient cell culture systems and animal models simulating the infection, much clarity toward understanding the pathogenetic mechanism of HEV has been developed. Also this facilitates the development of vaccines research or therapeutics. In this review, we highlight all the novel findings in every aspect of HEV with special emphasis on recently emerging chronic mode of infection with specific diagnosis and treatment regime with an optimistic hope to help virologists and/or liver specialists working in the field of viral hepatitis.
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Affiliation(s)
- Vikram Thakur
- Department of Virology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Radha Kanta Ratho
- Department of Virology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Swatantra Kumar
- Centre for Advanced Research, Faculty of Medicine, King George's Medical University, Lucknow, India
| | - Shailendra K Saxena
- Centre for Advanced Research, Faculty of Medicine, King George's Medical University, Lucknow, India
| | - Ishani Bora
- Department of Virology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Pryanka Thakur
- Department of Virology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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16
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Hepatitis E virus infection in liver transplant recipients: a descriptive literature review. Eur J Gastroenterol Hepatol 2020; 32:916-922. [PMID: 32091436 DOI: 10.1097/meg.0000000000001682] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Hepatitis E virus infection has been recognized as a rising hepatotropic viral infection in the developing countries but overlooked in the developed countries, due to its lower prevalence. However, hepatitis E virus prevalence is on rise in the liver transplant recipients due to immunosuppression, which needs prompt recognition by healthcare practitioners. Hepatitis E virus infection is commonly believed to be transmitted via an animal host; but in the post-liver transplant patients, it can also be acquired via blood and blood products transfusion and autochthonous route. Previous studies have shown the significance of hepatitis E virus infection in post-liver transplant, as the patients at a high risk of progressing to chronic hepatitis and cirrhosis. Pediatric patients are at higher risk of hepatitis E virus infection post-liver transplant. Specific hepatitis E virus genotypes have the potential for greater severity. The clinical manifestation of hepatitis E virus can also present as extrahepatic features which need high level of suspicion for early recognition and treatment. Treatment options of hepatitis E virus range from immunosuppressive drug minimization, ribavirin therapy to novel direct-acting antiviral regimens. Herein, we aim to explore epidemiology, prevalence, risk factor, diagnosis, and management of hepatitis E virus infection giving special attention to liver transplant recipients.
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17
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Jothimani D, Venugopal R, Vij M, Rela M. Post liver transplant recurrent and de novo viral infections. Best Pract Res Clin Gastroenterol 2020; 46-47:101689. [PMID: 33158469 PMCID: PMC7519014 DOI: 10.1016/j.bpg.2020.101689] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 09/22/2020] [Indexed: 01/31/2023]
Abstract
Survival following liver transplantation has changed dramatically owing to improvement in surgical techniques, peri-operative care and optimal immunosuppressive therapy. Post-Liver transplant (LT) de novo or recurrent viral infection continues to cause major allograft dysfunction, leading to poor graft and patient survival in untreated patients. Availability of highly effective antiviral drugs has significantly improved post-LT survival. Patients transplanted for chronic hepatitis B infection should receive life-long nucleos(t)ide analogues, with or without HBIg for effective viral control. Patients with chronic hepatitis C should be commenced on directly acting antiviral (DAA) drugs prior to transplantation. DAA therapy for post-LT recurrent hepatitis C infection is associated with close to 100% sustained virological response (SVR), irrespective of genotype. De novo chronic Hepatitis E infection is an increasingly recognised cause of allograft dysfunction in LT recipients. Untreated chronic HEV infection of the graft may lead to liver fibrosis and allograft failure. CMV and EBV can reactivate leading to systemic illness following liver transplantation. With COVID-19 pandemic, post-transplant patients are at risk of SARS-Co-V2 infection. Majority of the LT recipients require hospitalization, and the mortality in this population is around 20%. Early recognition of allograft dysfunction and identification of viral aetiology is essential in the management of post-LT de novo or recurrent infections. Optimising immunosuppression is an important step in reducing the severity of allograft damage in the treatment of post-transplant viral infections. Viral clearance or control can be achieved by early initiation of high potency antiviral therapy.
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Affiliation(s)
- Dinesh Jothimani
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India.
| | - Radhika Venugopal
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Mukul Vij
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Mohamed Rela
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
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18
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Nitta S, Takahashi K, Kawai-Kitahata F, Tsuchiya J, Sato A, Miyoshi M, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Kakinuma S, Watanabe M, Asahina Y. Time course alterations of virus sequences and immunoglobulin titers in a chronic hepatitis E patient. Hepatol Res 2020; 50:524-531. [PMID: 31883166 DOI: 10.1111/hepr.13480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Revised: 12/04/2019] [Accepted: 12/23/2019] [Indexed: 02/08/2023]
Abstract
AIM Hepatitis E virus (HEV) can cause chronic infection in immunocompromised hosts. However, the dynamics of HEV during persistent infection is not well understood. To elucidate time course alterations in virus sequences and anti-HEV antibodies during persistent infection, we analyzed the HEV sequences and titers of anti-HEV antibodies from a chronic hepatitis E patient. METHODS Serum samples were obtained from a chronic hepatitis E patient under corticosteroid therapy for neurological disease. The titers of anti-HEV antibodies (immunoglobulin A, immunoglobulin M, and immunoglobulin G) in serum samples were detected by enzyme immunoassay. The full or near-full nucleotide sequences of HEV isolated from consecutive serum samples were identified and compared. Phylogenetic analysis was also performed. RESULTS Alterations of anti-HEV antibodies from a chronic hepatitis E patient were different from those previously reported in acute hepatitis E patients. The virus sequence was unchanged in the period without treatment, but nucleotide mutations were observed after ribavirin treatment was started. In addition, the sequence of this strain had extremely high identity to that isolated from swine liver in Japan. CONCLUSIONS Virus mutations in HEV emerged after ribavirin treatment was started. Sequence analysis may useful for deciding the treatment strategy for chronic hepatitis E patients who did not eliminate the virus with 3 months of RBV treatment and inferring the origin of the infection. This report provides insights into the chronicity of hepatitis E, and the impact of persistent infection and ribavirin treatment on the emergence of virus mutations.
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Affiliation(s)
- Sayuri Nitta
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kazuaki Takahashi
- Department of Medical Sciences, Tokyo-Shinagawa Hospital, Tokyo, Japan.,Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Fukiko Kawai-Kitahata
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Jun Tsuchiya
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ayako Sato
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Masato Miyoshi
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Miyako Murakawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Itsui
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mina Nakagawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Seishin Azuma
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Sei Kakinuma
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,TMDU Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Asahina
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
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Abstract
Infection with the hepatitis E virus (HEV) is one of the most common causes, if not the most common, of acute hepatitis worldwide. In the last decade, we have learned that, in addition to the endemically and epidemically occurring form of hepatitis E, which is predominantly transmitted by contaminated drinking water and constitutes a significant health problem in resource-poor countries, there is a globally existing form of hepatitis E, which is a zoonosis and as such is primarily transmitted by the consumption of contaminated meat products. Although in most cases hepatitis E is subclinical or mild and self-limiting, pregnant women and patients with liver cirrhosis may have severe, occasionally even fatal disease, and immunocompromised individuals may develop chronic hepatitis E. Considering the substantial global health burden caused by HEV infection, it is surprising how limited our knowledge of hepatitis E pathology still is. In this article, we describe localization studies on HEV infection and discuss their implications for everyday diagnostics. Furthermore, we outline and discuss the spectrum of histologic changes, which can be found in HEV infection in various clinical contexts.
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20
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Fantilli AC, Trinks J, Marciano S, Zárate F, Balderramo DC, Wassaf MGM, Haddad L, Gadano A, Debes JD, Pisano MB, Ré VE. Unexpected high seroprevalence of hepatitis E virus in patients with alcohol-related cirrhosis. PLoS One 2019; 14:e0224404. [PMID: 31648288 PMCID: PMC6812777 DOI: 10.1371/journal.pone.0224404] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 10/12/2019] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Little is known about hepatitis E virus (HEV) infection in patients with cirrhosis. The aim of the present study was to describe the frequency of HEV infection and associated risk factors in patients with cirrhosis from Argentina. MATERIALS AND METHODS We evaluated HEV seroprevalence (IgG anti-HEV) and acute infections (IgM and RNA) in patients with cirrhosis (n = 140) vs. healthy controls (n = 300). Additionally, we compared the same outcomes in individuals with alcohol-related cirrhosis (n = 43) vs. patients with alcohol use disorder (without cirrhosis, n = 72). RESULTS The overall HEV seroprevalence in the cohort of subjects with cirrhosis was 25% (35/140), compared to 4% in the healthy control group [12/300; OR = 8; (95% CI = 4-15.99); p<0.05]. HEV seropositivity was significantly higher in alcohol-related cirrhosis compared to other causes of cirrhosis [39.5% vs. 12.4%; OR = 4.71; (95% CI = 1.9-11.6); p<0.05] and to healthy controls [OR = 15.7; (95% CI = 6.8-36.4); p = 0.0001]. The HEV seroprevalence in alcoholic-related cirrhosis vs. with alcohol use disorder was 39.5% vs. 12.5% [OR = 4.58; (95% CI = 1.81-11.58); p<0.001]. CONCLUSION We found a high seroprevalence of HEV in patients with cirrhosis and in individuals with alcohol use disorder. The simultaneous presence of both factors (cirrhosis + alcohol) showed more association to HEV infection. Larger studies with prospective follow up are needed to further clarify this interaction.
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Affiliation(s)
- Anabella C. Fantilli
- Instituto de Virología “Dr. J. M. Vanella”, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
| | - Julieta Trinks
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
- Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB)—CONICET—Instituto Universitario del Hospital Italiano (IUHI)—Hospital Italiano (HIBA), Buenos Aires, Argentina
| | - Sebastián Marciano
- Sección de Hepatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
- Departamento de Investigación, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | | | - Domingo C. Balderramo
- Departamento de Gastroenterología, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina
| | | | - Leila Haddad
- Sección de Hepatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Adrián Gadano
- Sección de Hepatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
- Departamento de Investigación, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - José D. Debes
- Department of Medicine, Division of Infectious Diseases and International Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America
| | - María B. Pisano
- Instituto de Virología “Dr. J. M. Vanella”, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
| | - Viviana E. Ré
- Instituto de Virología “Dr. J. M. Vanella”, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
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21
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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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Kamar N, Pischke S. Acute and Persistent Hepatitis E Virus Genotype 3 and 4 Infection: Clinical Features, Pathogenesis, and Treatment. Cold Spring Harb Perspect Med 2019; 9:cshperspect.a031872. [PMID: 29735575 DOI: 10.1101/cshperspect.a031872] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Hepatitis E virus (HEV) genotype (gt)3 and 4 infections are prevalent in industrialized and high-income countries. Although most HEV gt3 and gt4 infections are clinically silent, acute infection may be symptomatic in some patients. In persons with underlying liver disease and in elderly men, HEV infections may present as acute or acute-on-chronic liver failure. Chronic hepatitis may develop in immunosuppressed individuals, including transplant recipients, human immunodeficiency virus (HIV)-infected patients, and persons with hematologic malignancy undergoing chemotherapy, and may progress to life-threatening liver cirrhosis. Extrahepatic manifestations of infection may include neurological and renal disease. Although there is no approved specific therapy for the treatment of acute or chronic HEV gt3 or gt4 infection, off-label use of ribavirin appears to be capable of eliminating chronic HEV infection, and may reduce disease severity in patients suffering from acute liver failure.
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Affiliation(s)
- Nassim Kamar
- Department of Nephrology and Organ Transplantation, Université Paul Sabatier, Toulouse 31059, France
| | - Sven Pischke
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany
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Asif M, Hanif FM, Luck NH, Tasneem AA. Frequency of Hepatotropic Viruses Leading To Deranged Liver Function Tests in Renal Transplant Recipients. EXP CLIN TRANSPLANT 2019; 17:202-206. [PMID: 30777555 DOI: 10.6002/ect.mesot2018.p66] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES The preferred modality for renal replacement therapy is renal transplantation. Marked improvements in early graft survival and long-term graft function have made renal transplantation a more cost-effective alternative to dialysis. The presence of liver disease in the posttransplant period adversely affects graft function and survival. Determining the cause of deranged liver function tests can be helpful in treating the underlying cause, leading to improved graft survival and overall quality of life in patients after renal transplant. Here, we determined the frequency of hepatotropic viral infections leading to deranged liver function tests in renal transplant recipients. MATERIALS AND METHODS Our study included 132 patients with deranged liver function tests who had undergone renal transplant within the past 6 months. Reactivity and nonreactivity of hepatotropic viruses leading to deranged liver function tests were recorded. RESULTS Average age of patients was 37.17 ± 8.75 years. There were 84 male (63.64%) and 48 female (36.36%) patients. Rates of hepatitis C virus antibodies and hepatitis B surface antigen were 62.88% (83/132) and 37.12% (49/132), respectively, whereas no patients had hepatitis E virus immunoglobulin M antibodies or hepatitis A virus immunoglobulin M antibodies. CONCLUSIONS Among the hepatotropic viral infections leading to deranged liver function tests in renal transplant recipients, hepatitis B virus accounted for a small fraction. In contrast, hepatitis C virus was highly prevalent in transplant recipients who developed deranged liver function tests. Renal transplant recipients with hepatic viral infections have worse patient and allograft survival after transplant compared with noninfected renal transplant recipients. We recommend that transplant candidates be screened for hepatitis B and C virus infection, thus allowing increased graft survival and improved quality of life in renal transplant recipients.
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Affiliation(s)
- Madiha Asif
- From the Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan
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24
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Friebus-Kardash J, Eisenberger U, Ackermann J, Kribben A, Witzke O, Wenzel J, Rohn H, Fiedler M. Prevalence of active hepatitis E virus infection and efficacy of ribavirin treatment in renal allograft recipients. Transpl Infect Dis 2019; 21:e13088. [PMID: 30929308 DOI: 10.1111/tid.13088] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Revised: 02/17/2019] [Accepted: 03/17/2019] [Indexed: 12/26/2022]
Abstract
BACKGROUND Hepatitis E virus (HEV) genotype 3 infection frequently progresses to chronic disease with persisting HEV viremia in immunocompromised patients. Here, we evaluated the prevalence of HEV infection in renal allograft recipients and investigated the efficacy and tolerability of ribavirin monotherapy. METHODS A total of 947 recipients on average 8.7 years post transplant were screened for anti-HEV IgG, IgM and HEV-RNA. Sixteen HEV-viremic renal allograft recipients were treated with ribavirin for 12 weeks. HEV-RNA concentration, laboratory and clinical parameters were assessed at baseline, during therapy and 12 weeks after treatment cessation. HEV-genotyping was performed in all HEV-viremic patients. RESULTS Past HEV infection was detected serologically in 18% of the renal allograft recipients. Ongoing HEV replication was found in 16 recipients (all genotype 3). Unanimously, distinct HEV sequences were revealed in all HEV-viremic patients. At the start of ribavirin treatment, median HEV-RNA viral load was 4.3 × 106 (8000-5.0 × 106 ) IU/mL. Ninety-four percentage of HEV-infected allograft recipients showed a sustained virological response 12 weeks after treatment cessation. Ribavirin treatment was associated with rapid decrease in liver enzymes and rare occurrence of anemia. CONCLUSIONS Prevalence of active HEV infection is important in renal transplant patients without signs of nosocomial infection. Ribavirin treatment was safe and effective.
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Affiliation(s)
- Justa Friebus-Kardash
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Duisburg, Germany
| | - Ute Eisenberger
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Duisburg, Germany
| | - Jessica Ackermann
- Institute for Virology, University Hospital Essen, University Duisburg-Essen, Duisburg, Germany
| | - Andreas Kribben
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Duisburg, Germany
| | - Oliver Witzke
- Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Duisburg, Germany
| | - Jürgen Wenzel
- Institute for Clinical Microbiology and Hygiene, National Consultant Laboratory for HAV and HEV, University Hospital Regensburg, Regensburg, Germany
| | - Hana Rohn
- Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Duisburg, Germany
| | - Melanie Fiedler
- Institute for Virology, University Hospital Essen, University Duisburg-Essen, Duisburg, Germany
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25
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Hepatitis E Virus Infection in Lung Transplant Recipients: A Case Series. Transplant Proc 2019; 51:376-379. [DOI: 10.1016/j.transproceed.2018.10.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 10/23/2018] [Indexed: 01/05/2023]
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26
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Toward Systematic Screening for Persistent Hepatitis E Virus Infections in Transplant Patients. Transplantation 2019; 102:1139-1147. [PMID: 29953421 DOI: 10.1097/tp.0000000000002097] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Persistent hepatitis E virus genotype 3 (HEV G3) infections affect solid organ transplant (SOT) recipients and hematopoietic stem cell transplant (HSCT) recipients, but the burden in these cohorts in the United Kingdom is unknown. We established an audit to determine the point prevalence of HEV viremia in SOT and HSCT patients in the United Kingdom and compare different testing approaches to inform screening strategies. METHODS Between January 5, 2016, and September 21, 2016, 3044 patients undergoing therapeutic drug monitoring at a single transplant center were screened for HEV ribonucleic acid (RNA) in minipools. A total of 2822 patients who could be characterized included 2419 SOT patients, 144 HSCT patients and 259 patients with no available transplant history. HEV RNA-positive samples were characterized by serology and genomic phylogeny. HEV antigen (HEV-Ag) testing was performed on RNA-positive samples, 420 RNA-negative samples and 176 RNA-negative blood donor samples. RESULTS Nineteen of 2822 patients were viremic with G3 HEV giving a prevalence of 0.67%. The median alanine aminotransferase was significantly higher in the HEV viremic patients (P < 0.0001); however, 2 viremic patients had an alanine aminotransferase value within the normal range at the time of screening. The HEV-Ag assay identified 18/19 viremic patients and all those patients with proven viremia longer than 4 weeks. CONCLUSIONS Transplant recipients in the United Kingdom are at a low but significant risk of HEV infection. HEV-Ag detection could be an alternative to RNA detection where the goal is to identify established persistent HEV infection, particularly where expertise, facilities, or cost prohibit RNA testing.
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27
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Vanichanan J, Udomkarnjananun S, Avihingsanon Y, Jutivorakool K. Common viral infections in kidney transplant recipients. Kidney Res Clin Pract 2018; 37:323-337. [PMID: 30619688 PMCID: PMC6312768 DOI: 10.23876/j.krcp.18.0063] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 09/22/2018] [Accepted: 10/07/2018] [Indexed: 12/15/2022] Open
Abstract
Infectious complications have been considered as a major cause of morbidity and mortality after kidney transplantation, especially in the Asian population. Therefore, prevention, early detection, and prompt treatment of such infections are crucial in kidney transplant recipients. Among all infectious complications, viruses are considered to be the most common agents because of their abundance, infectivity, and latency ability. Herpes simplex virus, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, hepatitis B virus, BK polyomavirus, and adenovirus are well-known etiologic agents of viral infections in kidney transplant patients worldwide because of their wide range of distribution. As DNA viruses, they are able to reactivate after affected patients receive immunosuppressive agents. These DNA viruses can cause systemic diseases or allograft dysfunction, especially in the first six months after transplantation. Pretransplant evaluation and immunization as well as appropriate prophylaxis and preemptive approaches after transplant have been established in the guidelines and are used effectively to reduce the incidence of these viral infections. This review will describe the etiology, diagnosis, prevention, and treatment of viral infections that commonly affect kidney transplant recipients.
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Affiliation(s)
- Jakapat Vanichanan
- Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Suwasin Udomkarnjananun
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.,Renal Immunology and Therapeutic Apheresis Research Unit, Chulalongkorn University, Bangkok, Thailand
| | - Yingyos Avihingsanon
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.,Renal Immunology and Therapeutic Apheresis Research Unit, Chulalongkorn University, Bangkok, Thailand.,Excellence Center of Immunology and Immune-mediated Diseases, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Kamonwan Jutivorakool
- Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
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28
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Ankcorn M, Moreira F, Ijaz S, Symes A, Buckland MS, Workman S, Warburton F, Tedder RS, Lowe DM. Absence of Persistent Hepatitis E Virus Infection in Antibody-Deficient Patients Is Associated With Transfer of Antigen-Neutralizing Antibodies From Immunoglobulin Products. J Infect Dis 2018; 219:245-253. [DOI: 10.1093/infdis/jiy504] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Accepted: 08/16/2018] [Indexed: 02/07/2023] Open
Affiliation(s)
- Mike Ankcorn
- Blood Borne Virus Unit, Virus Reference Department, Public Health England
- Transfusion Microbiology, National Health Service Blood and Transplant
| | - Fernando Moreira
- Department of Clinical Immunology, Royal Free London National Health Service Foundation Trust
| | - Samreen Ijaz
- Blood Borne Virus Unit, Virus Reference Department, Public Health England
| | - Andrew Symes
- Department of Clinical Immunology, Royal Free London National Health Service Foundation Trust
| | - Matthew S Buckland
- Department of Clinical Immunology, Royal Free London National Health Service Foundation Trust
- Institute of Immunity and Transplantation, University College London, Royal Free Campus
| | - Sarita Workman
- Department of Clinical Immunology, Royal Free London National Health Service Foundation Trust
| | - Fiona Warburton
- Statistics, Modelling, and Economics Department, Public Health England
| | - Richard S Tedder
- Blood Borne Virus Unit, Virus Reference Department, Public Health England
- Transfusion Microbiology, National Health Service Blood and Transplant
- Division of Infection and Immunity, University College London, London, United Kingdom
| | - David M Lowe
- Department of Clinical Immunology, Royal Free London National Health Service Foundation Trust
- Institute of Immunity and Transplantation, University College London, Royal Free Campus
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29
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Abstract
Hepatitis E virus (HEV) is a well-known cause of acute hepatitis. Immunocompromised subjects, including liver transplant recipients, are considered to be at risk for HEV infection, which occasionally follows a chronic course. The diagnosis of HEV infection in these patients must be based on HEV RNA testing, as serology has variable performance. The aim of this study was to assess the prevalence of HEV infection in liver transplant recipients in Greece by means of HEV RNA testing. Liver transplant recipients followed in the sole transplant centre in Greece were prospectively included. HEV RNA was detected by real-time RT-PCR. Positive samples were further analysed using a nested reverse transcription RT-PCR kit, which amplifies a 137-nucleotide sequence within the ORF2/ORF3 overlapping region to detect the HEV genotype and perform phylogenetic analysis. The mean age of the included patients (n = 76) was 54 years. The most common indication for liver transplantation was viral hepatitis (57%). The majority of the patients (75%) received a calcineurin inhibitor as part of their immunosuppressive regimen and had normal liver enzymes. HEV RNA was found positive in only 1/76 (1.3%) patient. Phylogenetic analysis showed that the sequence clustered into the HEV genotype 3 clade. This patient experienced an acute hepatitis flare, which nonetheless did not become chronic. The prevalence of HEV infection in liver transplant recipients in Greece is similar (1.3%) to that reported previously in other countries. Transplant physicians should be aware of this condition and its associated consequences.
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30
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An Update on the Clinicopathologic Features and Pathologic Diagnosis of Hepatitis E in Liver Specimens. Adv Anat Pathol 2018; 25:273-281. [PMID: 29697415 DOI: 10.1097/pap.0000000000000195] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Infection with the hepatitis E virus (HEV) is globally seen a leading cause of hepatitis. Now increasingly recognized also in industrialized countries, hepatitis E constitutes a significant health problem worldwide. The patient's immune status determines the clinical course and histopathology of hepatitis E. In immunocompetent patients, hepatitis E usually follows an asymptomatic or subclinical course, but may also present with acute hepatitis. In contrast, immunocompromised patients may develop chronic hepatitis, and patients with preexisting liver diseases are at risk for liver decompensation with potentially fatal outcome. Whereas pathologists only occasionally encounter liver biopsies from immunocompetent individuals with hepatitis E, they are more likely exposed to biopsies from patients with preexisting liver disease or immunocompromised individuals. Histopathologic hallmarks of hepatitis E in immunocompetent patients comprise lobular disarray, lobular, and portal inflammation, as well as hepatocyte necrosis of varying extend and regeneration. Thus, it is similar to acute non-E viral hepatitis, yet further differential diagnoses include autoimmune hepatitis and drug-induced liver injury. Histopathologic findings of hepatitis E in preexisting liver disease are determined by the underlying pathology, but may be more severe. Histopathologic presentation of hepatitis E in immunocompromised patients is highly variable, ranging from minimal active hepatitis to chronic hepatitis with severe activity and progressive fibrosis. Taken together, the variability of the histologic features depending on the clinical context and the overlap with other liver diseases make the histopathologic diagnosis of hepatitis E challenging. Immunohistochemistry for HEV open reading frame 2 protein and molecular testing for HEV RNA are useful tissue-based ancillary tools.
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31
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von Wulffen M, Westhölter D, Lütgehetmann M, Pischke S. Hepatitis E: Still Waters Run Deep. J Clin Transl Hepatol 2018; 6:40-47. [PMID: 29577031 PMCID: PMC5862998 DOI: 10.14218/jcth.2017.00030] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2017] [Accepted: 08/19/2017] [Indexed: 12/11/2022] Open
Abstract
Hepatitis E is an infectious inflammatory disease of the liver caused by the hepatitis E virus (HEV), a single-stranded RNA virus. Today, it is estimated that there are more than 20 million HEV infections every year, leading to 3.3 million symptomatic cases and more than 56,000 deaths. For a long time it was believed that HEV was a travel-associated disease, endemic in developing countries with poor hygienic standards and unsafe water supply. However, over the past years, publications have demonstrated that autochthonous HEV infections in industrialized countries are far more common than previously thought. Awareness for HEV amongst health care practitioners in industrialized countries is still limited. This relatively rare disease is of great importance, especially in immunocompromised patients where it can cause chronic liver disease. This article comprehensively reviews current literature to give an overview on clinically important topics. It will focus on epidemiological aspects, acute and chronic HEV infection as well as extra-hepatic manifestations, diagnostic approach and treatment options. Furthermore, the article is concluded with a brief outlook on perspectives and urgent problems to be addressed in the future.
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Affiliation(s)
- Moritz von Wulffen
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Dirk Westhölter
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marc Lütgehetmann
- Institute for Medical Microbiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sven Pischke
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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32
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Zhang J, Zhao Q, Xia N. Prophylactic Hepatitis E Vaccine. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 948:223-246. [PMID: 27738988 DOI: 10.1007/978-94-024-0942-0_13] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Hepatitis E has been increasingly recognized as an underestimated global disease burden in recent years. Subpopulations with more serious infection-associated damage or death include pregnant women, patients with basic liver diseases, and elderly persons. Vaccine would be the most effective means for prevention of HEV infection. The lack of an efficient cell culture system for HEV makes the development of classic inactive or attenuated vaccine infeasible. Hence, the recombinant vaccine approaches are explored deeply. The neutralizing sites are located almost exclusively in the capsid protein, pORF2, of the virion. Based on pORF2, many vaccine candidates showed potential of protecting primate animals; two of them were tested in human and evidenced to be well tolerated in adults and highly efficacious in preventing hepatitis E. The world's first hepatitis E vaccine, Hecolin® (HEV 239 vaccine), was licensed in China and launched in 2012.
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Affiliation(s)
- Jun Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China.
| | - Qinjian Zhao
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, 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, Xiamen University, Xiamen, China
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33
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Abstract
Serological and nucleic acid tests for detecting hepatitis E virus (HEV) have been developed for both epidemiologic and diagnostic purposes. The laboratory diagnosis of HEV infection depends on the detection of HEV antigen, HEV RNA, and serum antibodies against HEV (immunoglobulin [Ig]A, IgM, and IgG). Anti-HEV IgM antibodies can be detected during the acute phase of the illness and can last approximately 4 or 5 months, representing recent exposure, whereas anti-HEV IgG antibodies can last more than 10 years, representing remote exposure. Thus, the diagnosis of acute infection is based on the presence of anti-HEV IgM, HEV antigen, and HEV RNA, while epidemiological investigations are mainly based on anti-HEV IgG. Although significant progress has been made in developing and optimizing different formats of HEV assays, improving their sensitivity and specificity, there are many shortcomings and challenges in inter-assay concordance, validation, and standardization. This article reviews the current knowledge on the diagnosis of HEV infection, including the most common available laboratory diagnostic techniques.
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Affiliation(s)
- Chenyan Zhao
- Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, No. 2 Tiantanxili, Dongcheng District, Beijing, 100050, China
| | - Youchun Wang
- Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, No. 2 Tiantanxili, Dongcheng District, Beijing, 100050, China.
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34
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Fang SY, Han H. Hepatitis E viral infection in solid organ transplant patients. Curr Opin Organ Transplant 2017; 22:351-355. [DOI: 10.1097/mot.0000000000000432] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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35
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Lenggenhager D, Weber A. Hepatitis E Virus and the Liver: Clinical Settings and Liver Pathology. Gastroenterol Clin North Am 2017; 46:393-407. [PMID: 28506371 DOI: 10.1016/j.gtc.2017.01.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Infection with hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide, now increasingly recognized also in nonendemic regions. Clinical manifestation of hepatitis E includes mostly asymptomatic/subclinical presentations or acute, self-limiting hepatitis, but also potentially fatal liver failure or chronic hepatitis in immunocompromised individuals. Accordingly, hepatitis E histolpathologic patterns range from an unremarkable histology over acute (cholestatic) hepatitis with variable degree of necrosis to chronic hepatitis with fibrosis. Awareness of hepatitis E and its differential diagnoses, knowledge of its clinico-pathologic manifestations and familiarity with its diagnostic tools will enable clinicians and pathologists to competently make this diagnosis.
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Affiliation(s)
- Daniela Lenggenhager
- Department of Pathology and Molecular Pathology, University and University Hospital Zurich, Schmelzbergstrasse 12, Zurich 8091, Switzerland
| | - Achim Weber
- Department of Pathology and Molecular Pathology, University and University Hospital Zurich, Schmelzbergstrasse 12, Zurich 8091, Switzerland.
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36
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Gardinali NR, Guimarães JR, Melgaço JG, Kevorkian YB, Bottino FDO, Vieira YR, da Silva ACDA, Pinto DP, da Fonseca LB, Vilhena LS, Uiechi E, da Silva MCC, Moran J, Marchevsky RS, Cruz OG, Otonel RAA, Alfieri AA, de Oliveira JM, Gaspar AMC, Pinto MA. Cynomolgus monkeys are successfully and persistently infected with hepatitis E virus genotype 3 (HEV-3) after long-term immunosuppressive therapy. PLoS One 2017; 12:e0174070. [PMID: 28328941 PMCID: PMC5362194 DOI: 10.1371/journal.pone.0174070] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 03/02/2017] [Indexed: 01/19/2023] Open
Abstract
Epidemiological studies found that hepatitis E virus genotype 3 (HEV-3) infection was associated with chronic hepatitis and cirrhosis in immunocompromised patients. Our study aimed to investigate the relationship between the host immunosuppressive status and the occurrence of HEV-related chronic hepatitis. Here we describe a successful experimental study, using cynomolgus monkeys previously treated with tacrolimus, a potent calcineurin inhibitor immunosuppressant, and infected with a Brazilian HEV-3 strain isolated from naturally infected pigs. HEV infected monkeys were followed up during 160 days post infection (dpi) by clinical signs; virological, biochemical and haematological parameters; and liver histopathology. The tacrolimus blood levels were monitored throughout the experiment. Immunosuppression was confirmed by clinical and laboratorial findings, such as: moderate weight loss, alopecia, and herpes virus opportunistic infection. In this study, chronic HEV infection was characterized by the mild increase of liver enzymes serum levels; persistent RNA viremia and viral faecal shedding; and liver histopathology. Three out of four immunosuppressed monkeys showed recurrent HEV RNA detection in liver samples, evident hepatocellular ballooning degeneration, mild to severe macro and microvesicular steatosis (zone 1), scattered hepatocellular apoptosis, and lobular focal inflammation. At 69 dpi, liver biopsies of all infected monkeys revealed evident ballooning degeneration (zone 3), discrete hepatocellular apoptosis, and at most mild portal and intra-acinar focal inflammation. At 160 dpi, the three chronically HEV infected monkeys showed microscopic features (piecemeal necrosis) corresponding to chronic hepatitis in absence of fibrosis and cirrhosis in liver parenchyma. Within 4-months follow up, the tacrolimus-immunosuppressed cynomolgus monkeys infected with a Brazilian swine HEV-3 strain exhibited more severe hepatic lesions progressing to chronic hepatitis without liver fibrosis, similarly as shown in tacrolimus-immunosuppressed solid organ transplant (SOT) recipients. The cause-effect relationship between HEV infection and tacrolimus treatment was confirmed in this experiment.
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Affiliation(s)
- Noemi Rovaris Gardinali
- Laboratório de Desenvolvimento Tecnológico em Virologia, Oswaldo Cruz, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
- * E-mail:
| | - Juliana Rodrigues Guimarães
- Laboratório de Desenvolvimento Tecnológico em Virologia, Oswaldo Cruz, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Juliana Gil Melgaço
- Laboratório de Desenvolvimento Tecnológico em Virologia, Oswaldo Cruz, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Yohan Britto Kevorkian
- Laboratório de Desenvolvimento Tecnológico em Virologia, Oswaldo Cruz, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Fernanda de Oliveira Bottino
- Laboratório de Desenvolvimento Tecnológico em Virologia, Oswaldo Cruz, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Yasmine Rangel Vieira
- Laboratório de Desenvolvimento Tecnológico em Virologia, Oswaldo Cruz, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Aline Campos de Azevedo da Silva
- Serviço de Equivalência e Farmacocinética –SEFAR, Vice-Presidência de Produção e Inovação em Saúde–VPPIS, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Douglas Pereira Pinto
- Serviço de Equivalência e Farmacocinética –SEFAR, Vice-Presidência de Produção e Inovação em Saúde–VPPIS, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Laís Bastos da Fonseca
- Serviço de Equivalência e Farmacocinética –SEFAR, Vice-Presidência de Produção e Inovação em Saúde–VPPIS, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Leandro Schiavo Vilhena
- Serviço de Equivalência e Farmacocinética –SEFAR, Vice-Presidência de Produção e Inovação em Saúde–VPPIS, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | | | - Maria Cristina Carlan da Silva
- Laboratório de Biologia Molecular de Patógenos (Virologia Molecular), Centro de Ciências Naturais e Humanas-CCNH, Universidade Federal do ABC-UFABC, São Bernardo do Campo, São Paulo, Brazil
| | - Julio Moran
- Dr. Julio Moran Laboratories, Ebmatingen, Zurich, Switzerland
| | - Renato Sérgio Marchevsky
- Laboratório de Neurovirulência, Instituto de Tecnologia em Imunobiológicos Bio-Manguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | | | | | - Amauri Alcindo Alfieri
- Laboratório de Virologia Animal, Departamento de Medicina Veterinária Preventiva Universidade Estadual de Londrina, Paraná, Brazil
| | - Jaqueline Mendes de Oliveira
- Laboratório de Desenvolvimento Tecnológico em Virologia, Oswaldo Cruz, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Ana Maria Coimbra Gaspar
- Laboratório de Desenvolvimento Tecnológico em Virologia, Oswaldo Cruz, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Marcelo Alves Pinto
- Laboratório de Desenvolvimento Tecnológico em Virologia, Oswaldo Cruz, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
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Elmasry S, Wadhwa S, Bang BR, Cook L, Chopra S, Kanel G, Kim B, Harper T, Feng Z, Jerome KR, Kahn JA, Saito T. Detection of Occult Hepatitis C Virus Infection in Patients Who Achieved a Sustained Virologic Response to Direct-Acting Antiviral Agents for Recurrent Infection After Liver Transplantation. Gastroenterology 2017; 152:550-553.e8. [PMID: 27838287 PMCID: PMC5285320 DOI: 10.1053/j.gastro.2016.11.002] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Revised: 11/02/2016] [Accepted: 11/03/2016] [Indexed: 12/16/2022]
Abstract
Occult infection with hepatitis C virus (HCV) is defined as the presence of the HCV genome in either liver tissue or peripheral blood monocytes, despite constant negative results from tests for HCV RNA in serum. We investigated whether patients who maintained a sustained virologic response 12 weeks after therapy (SVR12) with direct-acting antiviral (DAA) agents for recurrent HCV infection after liver transplantation had occult HCV infections. We performed a prospective study of 134 patients with recurrent HCV infection after liver transplantation who were treated with DAAs, with or without ribavirin, from 2014 through 2016 (129 patients achieved an SVR12). In >10% of the patients who achieved SVR12 (n = 14), serum levels of aminotransferases did not normalize during or after DAA therapy, or they normalized transiently but then increased sharply after DAA therapy. Of these 14 patients, 9 were assessed for occult HCV infection by reverse transcription quantitative polymerase chain reaction. This analysis revealed that 55% of these patients (n = 5) had an occult infection, with the detection of negative strand viral genome, indicating viral replication. These findings indicate the presence of occult HCV infection in some patients with abnormal levels of serum aminotransferases, despite SVR12 to DAAs for HCV infection after liver transplantation.
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Affiliation(s)
- Sandra Elmasry
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Sanya Wadhwa
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Bo-Ram Bang
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Linda Cook
- Department of Laboratory Medicine, School of Medicine, University of Washington, Seattle, Washington; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Shefali Chopra
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Gary Kanel
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Brian Kim
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Tammy Harper
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Zongdi Feng
- Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio
| | - Keith R Jerome
- Department of Laboratory Medicine, School of Medicine, University of Washington, Seattle, Washington; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Jeffrey A Kahn
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California.
| | - Takeshi Saito
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Molecular Microbiology and Immunology, University of Southern California, Research Center for Liver Diseases, Los Angeles, California.
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Hepatitis E Virus in Industrialized Countries: The Silent Threat. BIOMED RESEARCH INTERNATIONAL 2016; 2016:9838041. [PMID: 28070522 PMCID: PMC5192302 DOI: 10.1155/2016/9838041] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 11/07/2016] [Accepted: 11/15/2016] [Indexed: 12/11/2022]
Abstract
Hepatitis E virus (HEV) is the main cause of acute viral hepatitis worldwide. Its presence in developing countries has been documented for decades. Developed countries were supposed to be virus-free and initially only imported cases were detected in those areas. However, sporadic and autochthonous cases of HEV infection have been identified and studies reveal that the virus is worldwide spread. Chronic hepatitis and multiple extrahepatic manifestations have also been associated with HEV. We review the data from European countries, where human, animal, and environmental data have been collected since the 90s. In Europe, autochthonous HEV strains were first detected in the late 90s and early 2000s. Since then, serological data have shown that the virus infects quite frequently the European population and that some species, such as pigs, wild boars, and deer, are reservoirs. HEV strains can be isolated from environmental samples and reach the food chain, as shown by the detection of the virus in mussels and in contaminated pork products as sausages or meat. All these data highlight the need of studies directed to control the sources of HEV to protect immunocompromised individuals that seem the weakest link of the HEV epidemiology in industrialized regions.
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Fontana RJ, Engle RE, Scaglione S, Araya V, Shaikh O, Tillman H, Attar N, Purcell RH, Lee WM. The role of hepatitis E virus infection in adult Americans with acute liver failure. Hepatology 2016; 64:1870-1880. [PMID: 27215797 PMCID: PMC5115940 DOI: 10.1002/hep.28649] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Revised: 04/04/2016] [Accepted: 05/17/2016] [Indexed: 12/11/2022]
Abstract
UNLABELLED Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries, yet rarely identified in Western countries. Given that antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV-related ALF might be present and unrecognized in North American ALF patients. Serum samples of 681 adults enrolled in the U.S. Acute Liver Failure Study Group were tested for anti-HEV immunoglobulin (Ig) M and anti-HEV IgG levels. Subjects with a detectable anti-HEV IgM also underwent testing for HEV RNA. Mean patient age was 41.8 years, 32.9% were male, and ALF etiologies included acetaminophen (APAP) hepatotoxicity (29%), indeterminate ALF (23%), idiosyncratic drug-induced liver injury DILI (22%), acute hepatitis B virus infection (12%), autoimmune hepatitis (12%), and pregnancy-related ALF (2%). Three men ages 36, 39, and 70 demonstrated repeatedly detectable anti-HEV IgM, but all were HEV-RNA negative and had other putative diagnoses. The latter 2 subjects died within 3 and 11 days of enrollment whereas the 36-year-old underwent emergency liver transplantation on study day 2. At admission, 294 (43.4%) of the ALF patients were anti-HEV IgG positive with the seroprevalence being highest in those from the Midwest (50%) and lowest in those from the Southeast (28%). Anti-HEV IgG+ subjects were significantly older, less likely to have APAP overdose, and had a lower overall 3-week survival compared to anti-HEV IgG- subjects (63% vs. 70%; P = 0.018). CONCLUSION Acute HEV infection is very rare in adult Americans with ALF (i.e., 0.4%) and could not be implicated in any indeterminate, autoimmune, or pregnancy-related ALF cases. Past exposure to HEV with detectable anti-HEV IgG was significantly more common in the ALF patients compared to the general U.S. POPULATION (Hepatology 2016;64:1870-1880).
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Affiliation(s)
| | - Ronald E. Engle
- National Institute of Allergy and Infectious Diseases, Bethesda, MD
| | | | | | | | | | - Nahid Attar
- University of Texas Southwestern, Dallas, TX
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Pisano MB, Balderramo D, Wassaf MM, Lotto M, Carlino Y, Ré VE, Debes JD. Hepatitis E virus infection in patients on dialysis and in solid organ transplant recipients in Argentina: exploring associated risk factors. Arch Virol 2016; 162:787-792. [DOI: 10.1007/s00705-016-3171-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Accepted: 10/27/2016] [Indexed: 12/21/2022]
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Inagaki Y, Oshiro Y, Tanaka T, Yoshizumi T, Okajima H, Ishiyama K, Nakanishi C, Hidaka M, Wada H, Hibi T, Takagi K, Honda M, Kuramitsu K, Tanaka H, Tohyama T, Ikegami T, Imura S, Shimamura T, Nakayama Y, Urahashi T, Yamagishi K, Ohnishi H, Nagashima S, Takahashi M, Shirabe K, Kokudo N, Okamoto H, Ohkohchi N. A Nationwide Survey of Hepatitis E Virus Infection and Chronic Hepatitis E in Liver Transplant Recipients in Japan. EBioMedicine 2016; 2:1607-12. [PMID: 26870785 PMCID: PMC4740318 DOI: 10.1016/j.ebiom.2015.09.030] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 09/16/2015] [Accepted: 09/16/2015] [Indexed: 01/11/2023] Open
Abstract
Background Recently, chronic hepatitis E has been increasingly reported in organ transplant recipients in European countries. In Japan, the prevalence of hepatitis E virus (HEV) infection after transplantation remains unclear, so we conducted a nationwide cross-sectional study to clarify the prevalence of chronic HEV infection in Japanese liver transplant recipients. Methods A total of 1893 liver transplant recipients in 17 university hospitals in Japan were examined for the presence of immunoglobulin G (IgG), IgM and IgA classes of anti-HEV antibodies, and HEV RNA in serum. Findings The prevalence of anti-HEV IgG, IgM and IgA class antibodies was 2.9% (54/1893), 0.05% (1/1893) and 0% (0/1893), respectively. Of 1651 patients tested for HEV RNA, two patients (0.12%) were found to be positive and developed chronic infection after liver transplantation. In both cases, HEV RNA was also detected in one of the blood products transfused at the perioperative period. Analysis of the HEV genomes revealed that the HEV isolates obtained from the recipients and the transfused blood products were identical in both cases, indicating transfusion-transmitted HEV infection. Interpretation The prevalence of HEV antibodies in liver transplant recipients was 2.9%, which is low compared with the healthy population in Japan and with organ transplant recipients in European countries; however, the present study found, for the first time, two Japanese patients with chronic HEV infection that was acquired via blood transfusion during or after liver transplantation.
We conducted the multicenter survey for HEV infection in liver transplant recipients. Though the chronic HEV infection is rare, transfusion-transmitted cases were detected. Blood products can be a risk of chronic HEV infection in transplant recipients.
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Affiliation(s)
- Yuki Inagaki
- Division of Gastroenterological and Hepatobiliary Surgery, and Organ Transplantation, Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
| | - Yukio Oshiro
- Division of Gastroenterological and Hepatobiliary Surgery, and Organ Transplantation, Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
| | - Tomohiro Tanaka
- Organ Transplantation Service, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Hideaki Okajima
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Hospital, 54 Kawaharacho, Syogoin, Sakyu-ku, Kyoto 606-8507, Japan
| | - Kohei Ishiyama
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
| | - Chikashi Nakanishi
- Department of Transplantation, Reconstruction and Endoscopic Surgery, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan
| | - Masaaki Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| | - Hiroshi Wada
- Department of Surgery, Graduate School of Medicine, Osaka University, 2-15 Yamadaoka, Suita, Osaka 565-0871, Japan
| | - Taizo Hibi
- Department of Surgery, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-0016, Japan
| | - Kosei Takagi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikada-machi, Kita-ku, Okayama 700-8558, Japan
| | - Masaki Honda
- Department of Transplantation and Pediatric Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto-shi, Kumamoto 860-8556, Japan
| | - Kaori Kuramitsu
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan
| | - Hideaki Tanaka
- Department of Pediatric Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
| | - Taiji Tohyama
- Department of HPB and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa, To-on, Ehime 791-0295, Japan
| | - Toshihiko Ikegami
- Department of Transplant Surgery, Shinshu University, School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Satoru Imura
- Department of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Tsuyoshi Shimamura
- Division of Organ Transplantation, Hokkaido University Hospital, Kita 14, Jonishi 5-chome, Kita-ku, Sapporo, Hokkaido 060-8648, Japan
| | - Yoshimi Nakayama
- Department of Hepatobiliary Pancreatic Surgery, Juntendo University School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo 113-8431, Japan
| | - Taizen Urahashi
- Department of Transplant Surgery, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan
| | - Kazumasa Yamagishi
- Department of Public Health Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
| | - Hiroshi Ohnishi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, 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
| | - Ken Shirabe
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, 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
| | - Nobuhiro Ohkohchi
- Division of Gastroenterological and Hepatobiliary Surgery, and Organ Transplantation, Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
- Corresponding author.
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Hartl J, Wehmeyer MH, Pischke S. Acute Hepatitis E: Two Sides of the Same Coin. Viruses 2016; 8:E299. [PMID: 27827877 PMCID: PMC5127013 DOI: 10.3390/v8110299] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2016] [Revised: 10/04/2016] [Accepted: 10/17/2016] [Indexed: 12/12/2022] Open
Abstract
The relevance of acute hepatitis E virus (HEV) infections has been underestimated for a long time. In the past, HEV infection had been interpreted falsely as a disease limited to the tropics until the relevance of autochthonous HEV infections in the Western world became overt. Due to increased awareness, the incidence of diagnosed autochthonous HEV infections (predominantly genotype 3) in industrialized countries has risen within the last decade. The main source of infections in industrialized countries seems to be infected swine meat, while infections with the tropical HEV genotypes 1 and 2 usually are mainly transmitted fecal-orally by contaminated drinking water. In the vast majority of healthy individuals, acute HEV infection is either clinically silent or takes a benign self-limited course. In patients who develop a symptomatic HEV infection, a short prodromal phase with unspecific symptoms is followed by liver specific symptoms like jaundice, itching, uncoloured stool and darkened urine. Importantly, tropical HEV infections may lead to acute liver failure, especially in pregnant women, while autochthonous HEV infections may lead to acute-on-chronic liver failure in patients with underlying liver diseases. Immunosuppressed individuals, such as transplant recipients or human immunodeficiency virus (HIV)-infected patients, are at risk for developing chronic hepatitis E, which may lead to liver fibrosis and cirrhosis in the long term. Importantly, specific treatment options for hepatitis E are not approved by the regulation authorities, but off-label ribavirin treatment seems to be effective in the treatment of chronic HEV-infection and may reduce the disease severity in patients suffering from acute liver failure.
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Affiliation(s)
- Johannes Hartl
- First Medical Department, University Medical Center Hamburg-Eppendorf, University Hospital Hamburg Eppendorf (UKE), 20246 Hamburg, Germany.
| | - Malte H Wehmeyer
- First Medical Department, University Medical Center Hamburg-Eppendorf, University Hospital Hamburg Eppendorf (UKE), 20246 Hamburg, Germany.
| | - Sven Pischke
- First Medical Department, University Medical Center Hamburg-Eppendorf, University Hospital Hamburg Eppendorf (UKE), 20246 Hamburg, Germany.
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Nagashima S, Kobayashi T, Tanaka T, Tanggis, Jirintai S, Takahashi M, Nishizawa T, Okamoto H. Analysis of adaptive mutations selected during the consecutive passages of hepatitis E virus produced from an infectious cDNA clone. Virus Res 2016; 223:170-80. [DOI: 10.1016/j.virusres.2016.07.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2016] [Revised: 07/23/2016] [Accepted: 07/29/2016] [Indexed: 02/08/2023]
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Debes JD, Martínez Wassaf M, Pisano MB, Isa MB, Lotto M, Marianelli LG, Frassone N, Ballari E, Bohjanen PR, Hansen BE, Ré V. Increased Hepatitis E Virus Seroprevalence Correlates with Lower CD4+ Cell Counts in HIV-Infected Persons in Argentina. PLoS One 2016; 11:e0160082. [PMID: 27467394 PMCID: PMC4965084 DOI: 10.1371/journal.pone.0160082] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Accepted: 07/12/2016] [Indexed: 12/16/2022] Open
Abstract
Hepatitis E virus (HEV) is a single-stranded RNA virus that can cause hepatitis in an epidemic fashion. HEV usually causes asymptomatic or limited acute infections in immunocompetent individuals, whereas in immunosuppressed individuals such as transplant recipients, HEV can cause chronic infections. The risks and outcomes of HEV co-infection in patients infected with human immunodeficiency virus (HIV) are poorly characterized. We used a third generation immunoassay to measure serum IgG antibodies specific for HEV in 204 HIV-infected individuals from Argentina and a control group of 433 HIV-negative individuals. We found 15 of 204 (7.3%, 95%CI 3.74-10.96%) individuals in the HIV-positive group to have positive HEV IgG levels suggestive of previous infection, compared to 19 of 433 (4.4%, 95% CI 2.5-6.3%) individuals in the HIV-negative control group (p = 0.12). Among HIV-positive individuals, those with HEV seropositivity had lower CD4 counts compared to those that were HEV seronegative (average CD4 count of 234 vs 422 mm3, p = 0.01), indicating that patients with lower CD4 counts were more likely to be HEV IgG positive. Moreover, HEV seropositivity in patients with CD4 counts <200 mm3 was 16%, compared to 4.5% in those with CD4 counts >200 mm3 (p = 0.012). We found a positive PCR result for HEV in one individual. Our study found that increased seroprevalence of HEV IgG correlated with lower CD4 counts in HIV-infected patients in Argentina.
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Affiliation(s)
- José D. Debes
- Department of Medicine, University of Minnesota, Minneapolis, MN, United States of America
| | | | - María Belén Pisano
- Instituto de Virología “Dr. J. M. Vanella” Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Cordoba, Argentina
| | - María Beatriz Isa
- Instituto de Virología “Dr. J. M. Vanella” Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Cordoba, Argentina
| | - Martin Lotto
- Instituto de Virología “Dr. J. M. Vanella” Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Cordoba, Argentina
| | | | | | | | - Paul R. Bohjanen
- Department of Medicine, University of Minnesota, Minneapolis, MN, United States of America
| | - Bettina E. Hansen
- Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, the Netherlands
| | - Viviana Ré
- Instituto de Virología “Dr. J. M. Vanella” Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Cordoba, Argentina
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Hillebrandt KH, Arsenic R, Hofmann J, Eurich D, Gül S, Strücker B, Sauer IM, Pratschke J, Stockmann M, Raschzok N. Acute Graft Dysfunction 17 Years After Liver Transplant: A Challenging Clinical and Histologic Manifestation of Hepatitis E. EXP CLIN TRANSPLANT 2016; 16:348-351. [PMID: 27310664 DOI: 10.6002/ect.2015.0343] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Acute hepatitis E virus infection after liver transplant is a challenging clinical phenomenon. Due to its unspecific clinical and histological presentation, the diagnosis of acute or chronic hepatitis E virus infection can be difficult in unclear cases of elevated liver enzymes. Here, we report the case of a 56-year-old male patient who presented to our center for 17-year follow-up after liver transplant with α1-antitrypsin deficiency. The patient was asymptomatic but had remarkably increased transaminases and cholestasis parameters. Blood levels for immunosuppressives were in the normal range, and cholestasis and deteriorated liver perfusion were excluded by ultrasonographic examination. A liver biopsy was performed that was histologically interpreted as acute cellular rejection grade I. Accordingly, the patient was treated with 5-day high-dose intravenous steroids and increased doses of the maintenance immunosuppressive agents, resulting in the slow normalization of the liver enzymes. Extended laboratory examinations revealed presence of acute hepatitis E virus infection, and a retrospectively immunohistologic staining of the liver biopsy was positive for hepatitis E virus antigen. Acute hepatitis E virus infection can be a reason for acute allograft dysfunction after liver transplant. This differential diagnosis should be kept in mind, especially when graft dysfunction occurs long after transplant.
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Affiliation(s)
- K H Hillebrandt
- >From the General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany
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Trubiano JA, Johnson D, Sohail A, Torresi J. Travel vaccination recommendations and endemic infection risks in solid organ transplantation recipients. J Travel Med 2016; 23:taw058. [PMID: 27625399 DOI: 10.1093/jtm/taw058] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2016] [Accepted: 07/25/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Solid organ transplant (SOT) recipients are often heavily immunosuppressed and consequently at risk of serious illness from vaccine preventable viral and bacterial infections or with endemic fungal and parasitic infections. We review the literature to provide guidance regarding the timing and appropriateness of vaccination and pathogen avoidance related to the immunological status of SOT recipients. METHODS A PUBMED search ([Vaccination OR vaccine] AND/OR ["specific vaccine"] AND/OR [immunology OR immune response OR cytokine OR T lymphocyte] AND transplant was performed. A review of the literature was performed in order to develop recommendations on vaccination for SOT recipients travelling to high-risk destinations. RESULTS Whilst immunological failure of vaccination in SOT is primarily the result of impaired B-cell responses, the role of T-cells in vaccine failure and success remains unknown. Vaccination should be initiated at least 4 weeks prior to SOT or more than 6 months post-SOT. Avoidance of live vaccination is generally recommended, although some live vaccines may be considered in the specific situations (e.g. yellow fever). The practicing physician requires a detailed understanding of region-specific endemic pathogen risks. CONCLUSIONS We provide a vaccination and endemic pathogen guide for physicians and travel clinics involved in the care of SOT recipients. In addition, recommendations based on timing of anticipated immunological recovery and available evidence regarding vaccine immunogenicity in SOT recipients are provided to help guide pre-travel consultations.
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Affiliation(s)
- Jason A Trubiano
- Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia Department of Infectious Diseases, Peter MaCallum Cancer Centre, Melbourne, VIC, Australia Department of Medicine, University of Melbourne, Parkville, VIC, Australia
| | - Douglas Johnson
- Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia Department of Medicine, University of Melbourne, Parkville, VIC, Australia Department of General Medicine, Austin Health, Heidelberg, VIC, Australia
| | - Asma Sohail
- Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia
| | - Joseph Torresi
- Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia Eastern Infectious Diseases and Travel medicine, Knox Private Hospital, Boronia, VIC, Australia
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Kurihara T, Yoshizumi T, Itoh S, Harimoto N, Harada N, Ikegami T, Inagaki Y, Oshiro Y, Ohkohchi N, Okamoto H, Maehara Y. Chronic hepatitis E virus infection after living donor liver transplantation via blood transfusion: a case report. Surg Case Rep 2016; 2:32. [PMID: 27059470 PMCID: PMC4826363 DOI: 10.1186/s40792-016-0159-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2016] [Accepted: 04/04/2016] [Indexed: 12/12/2022] Open
Abstract
Although it occurs worldwide, hepatitis E virus (HEV) infection in developed countries is generally foodborne. HEV infection is subclinical in most individuals. Although fulminant liver failure may occur, progression to chronic hepatitis is rare. This study describes a 41-year-old man with liver cirrhosis caused by non-alcoholic steatohepatitis and hepatocellular carcinoma within the Milan criteria. His liver function was classified as Child-Pugh grade C. Living donor liver transplantation (LDLT) was performed, and he was discharged from the hospital on postoperative day (POD) 22. However, his alanine aminotransferase concentration began to increase on POD 60 and HEV infection was detected on POD 81. Retrospective assessments of stored blood samples showed that this patient became positive for HEV RNA on POD 3. The liver donor was negative for anti-HEV antibodies and HEV RNA. However, the platelet concentrate transfused into the liver recipient the day after LDLT was positive for HEV RNA. The patient remained positive for HEV infection for 10 months. Treatment with 800 mg/day ribavirin for 20 weeks reduced HEV RNA to an undetectable level. In conclusion, this report describes a patient infected with HEV through a blood transfusion after LDLT, who progressed to chronic hepatitis probably due to his immunosuppressed state and was treated well with ribavirin therapy.
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Affiliation(s)
- Takeshi Kurihara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Norifumi Harimoto
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Noboru Harada
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Toru Ikegami
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yuki Inagaki
- Division of Gastroenterological and Hepatobiliary Surgery, and Organ Transplantation, Department of Surgery, Faculty of Medicine, University of Tsukuba, Ibaragi, Japan
| | - Yukio Oshiro
- Division of Gastroenterological and Hepatobiliary Surgery, and Organ Transplantation, Department of Surgery, Faculty of Medicine, University of Tsukuba, Ibaragi, Japan
| | - Nobuhiro Ohkohchi
- Division of Gastroenterological and Hepatobiliary Surgery, and Organ Transplantation, Department of Surgery, Faculty of Medicine, University of Tsukuba, Ibaragi, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan
| | - Yoshihiko Maehara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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48
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Park WJ, Park BJ, Ahn HS, Lee JB, Park SY, Song CS, Lee SW, Yoo HS, Choi IS. Hepatitis E virus as an emerging zoonotic pathogen. J Vet Sci 2016; 17:1-11. [PMID: 27051334 PMCID: PMC4808633 DOI: 10.4142/jvs.2016.17.1.1] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Revised: 07/27/2015] [Accepted: 08/22/2015] [Indexed: 12/15/2022] Open
Abstract
Hepatitis E outbreaks are a serious public health concern in developing countries. The disease causes acute infections, primarily in young adults. The mortality rate is approximately 2%; however, it can exceed 20% in pregnant women in some regions in India. The causative agent, hepatitis E virus (HEV), has been isolated from several animal species, including pigs. HEV genotypes 3 and 4 have been isolated from both humans and animals, and are recognized as zoonotic pathogens. Seroprevalence studies in animals and humans indirectly suggest that HEV infections occur worldwide. The virus is primarily transmitted to humans via undercooked animal meats in developed countries. Moreover, transfusion- and transplantation-mediated HEV infections have recently been reported. This review summarizes the general characteristics of hepatitis E, HEV infection status in animals and humans, the zoonotic transmission modes of HEV, and HEV vaccine development status.
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Affiliation(s)
- Woo-Jung Park
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Byung-Joo Park
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Hee-Seop Ahn
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Joong-Bok Lee
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Seung-Yong Park
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Chang-Seon Song
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Sang-Won Lee
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Han-Sang Yoo
- Department of Infectious Diseases, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea
| | - In-Soo Choi
- Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
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49
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Wang X, Li M, Li S, Wu T, Zhang J, Xia N, Zhao Q. Prophylaxis against hepatitis E: at risk populations and human vaccines. Expert Rev Vaccines 2016; 15:815-27. [PMID: 26775537 DOI: 10.1586/14760584.2016.1143365] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatitis E is an emerging global disease caused by hepatitis E virus (HEV) infection. While in developing countries the infection was primarily due to poor sanitary conditions through intake of contaminated water or undercooked meats of infected animals, increasing cases of chronic hepatitis E resulting in rapidly progressive liver cirrhosis and end-stage liver disease have been reported in organ transplant patients or in immune compromised patients in developed countries. Fortunately, hepatitis E is now a vaccine preventable disease with a HEV239 based vaccine licensed for human use. Much work is needed to enable its use outside China. This review recounted the development process of the vaccine, outlined the critical quality attributes of the vaccine antigen and, most importantly, listed the populations at risk for HEV infection and the subsequent disease. These at risk populations could benefit the most from the vaccination if the vaccine is widely adopted.
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Affiliation(s)
- Xin Wang
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases , Xiamen University , Xiamen , PR China.,b School of Public Health , Xiamen University , Xiamen , PR China
| | - Min Li
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases , Xiamen University , Xiamen , PR China.,b School of Public Health , Xiamen University , Xiamen , PR China
| | - Shaowei Li
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases , Xiamen University , Xiamen , PR China.,b School of Public Health , Xiamen University , Xiamen , PR China.,c School of Life Science , Xiamen University , Xiamen , PR China
| | - Ting Wu
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases , Xiamen University , Xiamen , PR China.,b School of Public Health , Xiamen University , Xiamen , PR China.,c School of Life Science , Xiamen University , Xiamen , PR China
| | - Jun Zhang
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases , Xiamen University , Xiamen , PR China.,b School of Public Health , Xiamen University , Xiamen , PR China.,c School of Life Science , Xiamen University , Xiamen , PR China
| | - Ningshao Xia
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases , Xiamen University , Xiamen , PR China.,b School of Public Health , Xiamen University , Xiamen , PR China.,c School of Life Science , Xiamen University , Xiamen , PR China
| | - Qinjian Zhao
- a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases , Xiamen University , Xiamen , PR China.,b School of Public Health , Xiamen University , Xiamen , PR China
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50
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Marion O, Abravanel F, Lhomme S, Izopet J, Kamar N. Hepatitis E in Transplantation. Curr Infect Dis Rep 2016; 18:8. [DOI: 10.1007/s11908-016-0515-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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