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Lu J, Li Q, Zhang C, Li Z, Guo Q, Cao Z, Yao YF, Xie Q. Heterogeneity in the seroprevalence of hepatitis E virus among hospital attendees: a retrospective study in Shanghai, China. Infect Dis (Lond) 2025:1-11. [PMID: 40017260 DOI: 10.1080/23744235.2025.2471819] [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: 12/30/2024] [Revised: 02/11/2025] [Accepted: 02/20/2025] [Indexed: 03/01/2025] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) infection is endemic in China. However, there are scarce data of HEV infection among hospital attendees seeking medical treatment or examination for various reasons. OBJECTIVE We aim to investigate the prevalence and incidence of HEV infection by time, age, sex, and across departments in a tertiary hospital. METHODS Paired results of anti-HEV immunoglobulin G (IgG) and IgM of 31,181 unique subjects during 2021-2022 were analysed. RESULTS Overall seropositivity (95% confidence interval) of anti-HEV IgG and IgM was 41.25% (40.71%-41.80%) and 2.35% (2.19%-2.53%), respectively. Acute hepatitis E was more prevalent during winter-early spring and among adults aged 31-70. Anti-HEV IgG seroprevalence increased with age, levelling off at > 60 years of age. Not only the seropositivity, but also the levels of anti-HEV IgG were significantly lower in women than men of middle and old age. Young patients from the Department of Neurology had a significantly higher ratio of past HEV infection, while patients with manifestations of hepatitis, gastrointestinal symptoms or hematological diseases had higher seropositivity of anti-HEVIgM and should have high priority to HEV screening. CONCLUSION Heterogeneity of HEV seroprevalence was noted at different times of the year, between sexes, among age groups and across departments in general hospital. The concentration of HEV-infected patients in a few departments supports a more focused screening strategy in health-care settings.
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Affiliation(s)
- Jie Lu
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Li
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chenxi Zhang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ziqiang Li
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Guo
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhujun Cao
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu-Feng Yao
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Laboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Yu B, Zhu Y, Jin Z, Han F, Lv F. A case of thrombotic thrombocytopenic purpura induced by acute hepatitis E and successfully controlled by lymphoplasmapheresis plus rituximab. Virol J 2025; 22:39. [PMID: 39955583 PMCID: PMC11829560 DOI: 10.1186/s12985-025-02649-2] [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: 12/16/2024] [Accepted: 02/03/2025] [Indexed: 02/17/2025] Open
Abstract
BACKGROUND Thrombocytopenia is a common extrahepatic manifestation of hepatitis E virus (HEV) infection and is usually transient and self-limited. Thrombotic thrombocytopenic purpura (TTP) is a rare and lethal blood disorder characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ involvement. The link between HEV infection and TTP is still unclear. CASE PRESENTATION A 74-year-old female was referred to our hospital with complaints of fever, fatigue, nausea and jaundice for 10 days. Liver dysfunction, positive IgM and IgG of HEV, and HEV-RNA viremia prompted the diagnosis of acute hepatitis E, which was followed by a dramatic decline in the platelet count. The presence of schistocytes in the peripheral blood smear, along with decreased ADAMTS13 activity, strongly suggested a diagnosis of TTP. Combination therapy, including 2 courses of lymphoplasmapheresis (LPE), 4 courses of therapeutic plasma exchange, glucocorticoids and rituximab, was applied and contributed to the recovery of platelet. No recurrence of TTP was observed during the follow-up period. To date, this is first patient who developed the initial episode of TTP during the course of HEV viremia. In the meanwhile, LPE was used for the first time in the treatment of HEV-associated TTP. CONCLUSIONS This case highlights the necessity of ruling out TTP in hepatitis E patients with newly developed and severe thrombocytopenia and the values of LPE plus rituximab in treating such patients.
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Affiliation(s)
- Binfeng Yu
- Department of Liver and Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Yongfen Zhu
- Department of Liver and Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Zhihua Jin
- Department of Liver and Infectious Diseases, Shaoxing Central Hospital, Shaoxing, China
| | - Fei Han
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Fangfang Lv
- Department of Liver and Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China.
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Guerrero-Vadillo M, Peñuelas M, Carmona R, León-Gómez I, Varela C. Increasing trends in hepatitis E hospitalisations in Spain, 1997 to 2019. Euro Surveill 2024; 29:2400118. [PMID: 39450516 PMCID: PMC11513759 DOI: 10.2807/1560-7917.es.2024.29.43.2400118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 07/16/2024] [Indexed: 10/26/2024] Open
Abstract
BackgroundHepatitis E, a viral hepatitis caused mainly by the ingestion of raw or undercooked food, is not a notifiable disease in Spain.AimTo analyse the temporal trends, epidemiological characteristics and factors associated with severe disease from hepatitis E hospitalisations in Spain from 1997 to 2019.MethodsHospitalisation records were obtained from the Spanish National Hospital Discharge Database. Temporal trends and seasonality were analysed by Poisson regression in years 1997-2015 and 2016-19, given changes in hospital discharge databases. Multivariate logistic regression was used to identify factors associated with severe disease.ResultsHepatitis E hospitalisation incidence increased from 0.22 cases per 1,000,000 inhabitants in 1997 to a maximum of 2.95 in 2018. Seasonality was observed during 2016-19 period, with more cases in the second and third quarters of the year. The incidence was higher in men vs women, and in the population aged over 40 years. Factors independently associated with death were age ≥ 50 years (adjusted odds ratio (aOR): 2.43), chronic liver disease (aOR: 4.29), HIV infection (aOR: 3.00) and hepatitis B/C (aOR: 2.11).ConclusionsHepatitis E hospitalisations have increased in Spain in recent years, being more severe in cases with older age, chronic hepatic diseases and HIV infection. A greater incidence in men over 40 years and a possible seasonality were observed. Further studies are needed to assess the seasonality, geographical distribution and impact of the disease to guide public health actions for prevention and control.
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Affiliation(s)
- María Guerrero-Vadillo
- CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III (CIBERESP, ISCIII), Madrid, Spain
- Departamento de Enfermedades Transmisibles, Centro Nacional de Epidemiología (CNE), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Programa de Doctorado en Ciencias Biomédicas y Salud Pública, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain
| | - Marina Peñuelas
- CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III (CIBERESP, ISCIII), Madrid, Spain
- Departamento de Enfermedades Transmisibles, Centro Nacional de Epidemiología (CNE), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Rocío Carmona
- Departamento de Enfermedades Transmisibles, Centro Nacional de Epidemiología (CNE), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Inmaculada León-Gómez
- CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III (CIBERESP, ISCIII), Madrid, Spain
- Departamento de Enfermedades Transmisibles, Centro Nacional de Epidemiología (CNE), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Carmen Varela
- CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III (CIBERESP, ISCIII), Madrid, Spain
- Departamento de Enfermedades Transmisibles, Centro Nacional de Epidemiología (CNE), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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Letafati A, Taghiabadi Z, Roushanzamir M, Memarpour B, Seyedi S, Farahani AV, Norouzi M, Karamian S, Zebardast A, Mehrabinia M, Ardekani OS, Fallah T, Khazry F, Daneshvar SF, Norouzi M. From discovery to treatment: tracing the path of hepatitis E virus. Virol J 2024; 21:194. [PMID: 39180020 PMCID: PMC11342613 DOI: 10.1186/s12985-024-02470-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Accepted: 08/14/2024] [Indexed: 08/26/2024] Open
Abstract
The hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide. HEV is classified into eight genotypes, labeled HEV-1 through HEV-8. Genotypes 1 and 2 exclusively infect humans, while genotypes 3, 4, and 7 can infect both humans and animals. In contrast, genotypes 5, 6, and 8 are restricted to infecting animals. While most individuals with a strong immune system experience a self-limiting infection, those who are immunosuppressed may develop chronic hepatitis. Pregnant women are particularly vulnerable to severe illness and mortality due to HEV infection. In addition to liver-related complications, HEV can also cause extrahepatic manifestations, including neurological disorders. The immune response is vital in determining the outcome of HEV infection. Deficiencies in T cells, NK cells, and antibody responses are linked to poor prognosis. Interestingly, HEV itself contains microRNAs that regulate its replication and modify the host's antiviral response. Diagnosis of HEV infection involves the detection of HEV RNA and anti-HEV IgM/IgG antibodies. Supportive care is the mainstay of treatment for acute infection, while chronic HEV infection may be cleared with the use of ribavirin and pegylated interferon. Prevention remains the best approach against HEV, focusing on sanitation infrastructure improvements and vaccination, with one vaccine already licensed in China. This comprehensive review provides insights into the spread, genotypes, prevalence, and clinical effects of HEV. Furthermore, it emphasizes the need for further research and attention to HEV, particularly in cases of acute hepatitis, especially among solid-organ transplant recipients.
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Affiliation(s)
- Arash Letafati
- Department of Virology, Faculty of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran.
| | - Zahra Taghiabadi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Mahshid Roushanzamir
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
- Department of Pharmacological and Biomolecular Science, University of Milan, Milan, Italy
| | - Bahar Memarpour
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
- Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Saba Seyedi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | | | - Masoomeh Norouzi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Saeideh Karamian
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Arghavan Zebardast
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Marzieh Mehrabinia
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Omid Salahi Ardekani
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Tina Fallah
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Fatemeh Khazry
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Samin Fathi Daneshvar
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Mehdi Norouzi
- Department of Virology, Faculty of Public Health, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
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Ritter M, Yomade O, Holtz BO, Deinhardt-Emmer S, McLean AL, Hartinger S, Bechwar J, Schwab M, Huss A, Mawrin C, Axer H, Schrenk KG, Reuken PA, Mäurer I. Chronic hepatitis E virus-induced spinal cord atrophy in a patient with chronic lymphatic leukemia: a case report and interdisciplinary management proposal. Front Immunol 2024; 15:1445944. [PMID: 39131153 PMCID: PMC11310032 DOI: 10.3389/fimmu.2024.1445944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Accepted: 07/08/2024] [Indexed: 08/13/2024] Open
Abstract
Background The hepatitis E virus (HEV) can cause acute viral hepatitis with or without neurological manifestations, and occasionally progresses to chronic infection in immunocompromised individuals. The management of chronic HEV infection in cancer patients may be challenging due to the complex immunological constellation. Furthermore, the diagnostic workflow and the impact on quality of life of neurological HEV manifestations in immunocompromised patients have not been sufficiently delineated previously. Case description A 61-year-old male with systemically treated chronic lymphocytic leukemia (CLL) experienced a slowly progressive atrophy of the spinal cord due to a chronic HEV infection. Despite continuous antiviral treatment with ribavirin, the patient's neurological condition continued to deteriorate, particularly following subsequent attempts to treat CLL. Treatment with obinutuzumab resulted in acute bowel and urinary retention and a further deterioration of motor skills, prompting the discontinuation of obinutuzumab. The patient's neurological status improved after the administration of intravenous immunoglobulins. Conclusion This case study provides a comprehensive long-term follow-up of a cancer patient with chronic HEV infection and associated CNS involvement, which resulted in progressive neurological disability over several years. The challenges faced in diagnosing new neurological symptoms in patients undergoing immunosuppressive cancer treatment underscore the need for an interdisciplinary diagnostic approach that includes HEV testing. We propose a diagnostic pathway for future validation in immunocompromised cohorts presenting with neurological symptoms, emphasizing its potential to enhance clinical outcomes.
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Affiliation(s)
- Marvin Ritter
- Department of Neurology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Olaposi Yomade
- Department of Hematology and Medical Oncology, Clinic of Internal Medicine II, Jena University Hospital, Jena, Germany
- Comprehensive Cancer Center Central Germany (CCCG), Jena, Germany
| | - Ben-Ole Holtz
- Department of Neurology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Stefanie Deinhardt-Emmer
- Institute of Medical Microbiology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Aaron Lawson McLean
- Comprehensive Cancer Center Central Germany (CCCG), Jena, Germany
- Department of Neurosurgery, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Stefanie Hartinger
- Department of Neurology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
- Comprehensive Cancer Center Central Germany (CCCG), Jena, Germany
| | - Julia Bechwar
- Department of Neurology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Matthias Schwab
- Department of Neurology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - André Huss
- Department of Neurology, University Hospital of Ulm, Ulm, Germany
| | - Christian Mawrin
- Department of Neuropathology, Otto von Guericke University Magdeburg, Magdeburg, Germany
- Department of Pathology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Hubertus Axer
- Department of Neurology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Karin G. Schrenk
- Department of Hematology and Medical Oncology, Clinic of Internal Medicine II, Jena University Hospital, Jena, Germany
- Comprehensive Cancer Center Central Germany (CCCG), Jena, Germany
| | - Philipp A. Reuken
- Department of Gastroenterology, Hepatology, and Infectious Diseases, Clinic of Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - Irina Mäurer
- Department of Neurology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
- Comprehensive Cancer Center Central Germany (CCCG), Jena, Germany
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Kim SJ, Moon J. Narrative Review of the Safety of Using Pigs for Xenotransplantation: Characteristics and Diagnostic Methods of Vertical Transmissible Viruses. Biomedicines 2024; 12:1181. [PMID: 38927388 PMCID: PMC11200752 DOI: 10.3390/biomedicines12061181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 05/22/2024] [Accepted: 05/24/2024] [Indexed: 06/28/2024] Open
Abstract
Amid the deepening imbalance in the supply and demand of allogeneic organs, xenotransplantation can be a practical alternative because it makes an unlimited supply of organs possible. However, to perform xenotransplantation on patients, the source animals to be used must be free from infectious agents. This requires the breeding of animals using assisted reproductive techniques, such as somatic cell nuclear transfer, embryo transfer, and cesarean section, without colostrum derived in designated pathogen-free (DPF) facilities. Most infectious agents can be removed from animals produced via these methods, but several viruses known to pass through the placenta are not easy to remove, even with these methods. Therefore, in this narrative review, we examine the characteristics of several viruses that are important to consider in xenotransplantation due to their ability to cross the placenta, and investigate how these viruses can be detected. This review is intended to help maintain DPF facilities by preventing animals infected with the virus from entering DPF facilities and to help select pigs suitable for xenotransplantation.
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Affiliation(s)
- Su-Jin Kim
- Apures Co., Ltd., 44, Hansan-gil, Cheongbuk-eup, Pyeongtaek-si 17792, Gyeonggi-do, Republic of Korea;
| | - Joonho Moon
- Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
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Luo Q, Chen J, Zhang Y, Xu W, Liu Y, Xie C, Peng L. Viral hepatitis E: Clinical manifestations, treatment, and prevention. LIVER RESEARCH 2024; 8:11-21. [PMID: 39959034 PMCID: PMC11771268 DOI: 10.1016/j.livres.2024.01.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 11/17/2023] [Accepted: 01/03/2024] [Indexed: 02/18/2025]
Abstract
Hepatitis E is a globally distributed infection that varies in seroprevalence between developed and developing regions. In the less developed regions of Asia and Africa, a high seropositivity rate has been reported for hepatitis E virus (HEV) antibodies. Although acute hepatitis E is often self-limited and has a favorable prognosis, some populations experience severe manifestations, which may progress to liver failure. Moreover, some immunocompromised patients are at risk of developing chronic HEV infection and cirrhosis. Proactive screening, reducing misdiagnosis, improving patient management, timely antiviral therapy for severe and chronic cases, and vaccination of high-risk groups are important measures to reduce the morbidity of hepatitis E. This review focused on the clinical presentation, management, and prevention of hepatitis E.
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Affiliation(s)
- Qiumin Luo
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Jia Chen
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yeqiong Zhang
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Wenxiong Xu
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Ying Liu
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Chan Xie
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Liang Peng
- Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
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Ripellino P, Lascano AM, Scheidegger O, Schilg‐Hafer L, Schreiner B, Tsouni P, Vicino A, Peyer A, Humm AM, Décard BF, Pianezzi E, Zezza G, Sparasci D, Hundsberger T, Dietmann A, Jung H, Kuntzer T, Wilder‐Smith E, Martinetti‐Lucchini G, Petrini O, Fontana S, Gowland P, Niederhauser C, Gobbi C. Neuropathies related to hepatitis E virus infection: A prospective, matched case-control study. Eur J Neurol 2024; 31:e16030. [PMID: 37548584 PMCID: PMC11235744 DOI: 10.1111/ene.16030] [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: 05/23/2023] [Revised: 07/11/2023] [Accepted: 08/03/2023] [Indexed: 08/08/2023]
Abstract
BACKGROUND Acute hepatitis E virus (HEV) infection has recently emerged as a potential trigger for acute dysimmune neuropathies, but prospective controlled studies are lacking. AIMS To compare the frequency of concomitant acute HEV infection in patients with neuralgic amyotrophy (NA), Guillain-Barré syndrome (GBS), and Bell's palsy with a matched control population. METHODS Swiss multicenter, prospective, observational, matched case-control study over 3 years (September 2019-October 2022). Neurological cases with NA, GBS, or Bell's palsy were recruited within 1 month of disease onset. Healthy controls were matched for age, sex, geographical location, and timing of blood collection. Diagnostic criteria for acute hepatitis E were reactive serum anti-HEV IgM and IgG assays (ELISA test) and/or HEV RNA detection in serum by real-time polymerase chain reaction (RT-PCR). RT-PCR was performed on sera to confirm IgM positivity. RESULTS We included 180 patients (59 GBS, 51 NA, 70 Bell's palsy cases) and corresponding matched controls (blood donors) with median age 51 years for both groups and equal gender distribution. Six IgM+ cases were detected in the NA, two in the GBS, and none in the Bell's palsy group. Two controls were anti-HEV IgM-positive. At disease onset, most cases with acute HEV infection had increased liver enzymes. A moderate association (p = 0.027, Fisher's exact test; Cramér's V = -0.25) was observed only between acute HEV infection and NA. CONCLUSION This prospective observational study suggests an association between concomitant acute HEV infection and NA, but not with GBS or Bell's palsy.
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Affiliation(s)
- Paolo Ripellino
- Department of NeurologyNeurocenter of Southern Switzerland EOCLuganoSwitzerland
- Faculty of Biomedical SciencesUniversità della Svizzera ItalianaLuganoSwitzerland
| | - Agustina Maria Lascano
- Neurology Division, Department of Clinical NeuroscienceUniversity Hospitals of Geneva and Faculty of Medicine, University of GenevaGenevaSwitzerland
| | - Olivier Scheidegger
- Department of Neurology, InselspitalBern University Hospital and University of BernBernSwitzerland
| | | | - Bettina Schreiner
- Department of NeurologyUniversity and Hospital ZurichZurichSwitzerland
| | | | - Alex Vicino
- Nerve‐Muscle Unit, Neurology Service, Department of Clinical NeurosciencesLausanne University Hospital and University of LausanneLausanneSwitzerland
| | | | - Andrea Monika Humm
- Department of Medicine, Neurology UnitHFR Fribourg Cantonal HospitalFribourgSwitzerland
| | | | | | - Giulia Zezza
- Laboratory of Microbiology EOCBellinzonaSwitzerland
| | - Davide Sparasci
- Department of NeurologyNeurocenter of Southern Switzerland EOCLuganoSwitzerland
| | | | - Anelia Dietmann
- Department of Neurology, InselspitalBern University Hospital and University of BernBernSwitzerland
| | - Hans Jung
- Department of NeurologyUniversity and Hospital ZurichZurichSwitzerland
| | - Thierry Kuntzer
- Nerve‐Muscle Unit, Neurology Service, Department of Clinical NeurosciencesLausanne University Hospital and University of LausanneLausanneSwitzerland
| | - Einar Wilder‐Smith
- Department of Neurology, InselspitalBern University Hospital and University of BernBernSwitzerland
- Cantonal HospitalLucerneSwitzerland
| | | | - Orlando Petrini
- University of Applied Sciences and Arts of Southern SwitzerlandBellinzonaSwitzerland
| | - Stefano Fontana
- Blood Transfusion Service SRC Southern SwitzerlandLuganoSwitzerland
- Interregional Blood Transfusion SRCBernSwitzerland
| | | | - Christoph Niederhauser
- Interregional Blood Transfusion SRCBernSwitzerland
- Institute for Infectious DiseasesUniversity of BernBernSwitzerland
| | - Claudio Gobbi
- Department of NeurologyNeurocenter of Southern Switzerland EOCLuganoSwitzerland
- Faculty of Biomedical SciencesUniversità della Svizzera ItalianaLuganoSwitzerland
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Iqbal H, Mehmood BF, Sohal A, Roytman M. Hepatitis E infection: A review. World J Virol 2023; 12:262-271. [PMID: 38187497 PMCID: PMC10768387 DOI: 10.5501/wjv.v12.i5.262] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/23/2023] [Accepted: 12/05/2023] [Indexed: 12/25/2023] Open
Abstract
Hepatitis E virus (HEV) is a small non-enveloped virus that is transmitted via the fecal-oral route. It is a highly common cause of acute hepatitis, particularly in low to middle income regions of Asia, Africa, and Central America. Most cases are self-limited, and symptomatic patients usually present with acute icteric hepatitis. A subset of patients including pregnant women, older men, those with pre-existing liver disease and immunocompromised patients however, may develop severe disease and hepatic failure. Immunocompromised patients are also at risk for chronic infection, and their immunosuppression should be decreased in order to facilitate viral clearance. HEV can also present with a variety of extra-intestinal manifestations including neurological, renal, hematological, and pancreatic derangements. The gold standard of diagnosis is HEV ribonucleic acid detection via nucleic acid amplification testing. Currently, there are no approved treatments for Hepatitis E, though ribavirin is the most commonly used agent to reduce viral load. Studies assessing the safety and efficacy of other antiviral agents for HEV are currently underway. HEV vaccination has been approved in China, and is currently being investigated in other regions as well. This review article aims to discuss the epidemiology, pathogenesis, presentation, diagnosis, complications, and treatment of Hepatitis E infection.
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Affiliation(s)
- Humzah Iqbal
- Department of Internal Medicine, University of California San Francisco, Fresno, CA 93701, United States
| | - Bilal Fazal Mehmood
- Department of Internal Medicine, University of California San Francisco, Fresno, CA 93701, United States
| | - Aalam Sohal
- Department of Hepatology, Liver Institute Northwest, Seattle, WA 98105, United States
| | - Marina Roytman
- Department of Gastroenterology and Hepatology, University of California San Francisco, Fresno, CA 93701, United States
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Orozco-Cordoba J, Mazas C, Du Pont G, Lamoyi E, Cárdenas G, Fierro NA. Viral Biology and Immune Privilege in the Development of Extrahepatic Manifestations During Hepatitis E Virus Infection. Viral Immunol 2023; 36:627-641. [PMID: 38064537 DOI: 10.1089/vim.2023.0096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2023] Open
Abstract
Hepatitis E virus (HEV) exhibits tropism toward hepatocytes and thus affects the liver; however, HEV may also affect other tissues, including the heart, kidneys, intestines, testicles, and central nervous system. To date, the pathophysiological links between HEV infection and extrahepatic manifestations have not yet been established. Considering that HEV infects multiple types of cells, the direct effects of virus replication in peripheral tissues represent a plausible explanation for extrahepatic manifestations. In addition, since the immune response is crucial in the development of the disease, the immune characteristics of affected tissues should be revisited to identify commonalities explaining the effects of the virus. This review summarizes the most recent advances in understanding the virus biology and immune-privileged status of specific tissues as major elements for HEV replication in diverse organs. These discoveries may open avenues to explain the multiple extrahepatic manifestations associated with HEV infection and ultimately to design effective strategies for infection control.
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Affiliation(s)
- Javier Orozco-Cordoba
- Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City, Mexico
| | - Camila Mazas
- Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City, Mexico
| | - Gisela Du Pont
- Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City, Mexico
| | - Edmundo Lamoyi
- Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City, Mexico
| | - Graciela Cárdenas
- Departamento de Neuroinfectología, Instituto Nacional de Neurología Manuel Velasco Suárez, Mexico City, Mexico
| | - Nora A Fierro
- Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City, Mexico
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Lv F, Zhao Y, Yang XD, Chen HZ, Ren WY, Chen LX, Yi QQ, Zheng W, Pan HY. Acute Hepatitis E Induced the First Episode of Immune-Mediated Thrombotic Thrombocytopenic Purpura: The First Case Report. Infect Drug Resist 2023; 16:5149-5154. [PMID: 37581168 PMCID: PMC10423562 DOI: 10.2147/idr.s418430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 07/22/2023] [Indexed: 08/16/2023] Open
Abstract
Purpose Hepatitis E virus infection mainly presents with liver-related symptoms, and multiple studies have shown that hepatitis E virus infection can also induce extrahepatic-related symptoms. Thrombotic thrombocytopenic purpura is an uncommon and fatal thrombotic microangiopathy characterized by severe thrombocytopenia, organ damage, and microangiopathic haemolytic anaemia. We report the first case in which acute hepatitis E induced the first episode of immune-mediated thrombotic thrombocytopenic purpura. Patients and Methods A 53-year-old male was admitted to our emergency department with fever, thrombocytopenia, and abnormal liver function. Laboratory tests revealed significant bilirubin, AST, and ALT elevations, renal impairment, positive anti-HEV IgM and IgG antibody results, schistocytes on the blood smear, 0% ADAMTS-13 activity, and positive ADAMTS13 inhibitor results. He was diagnosed with acute hepatitis E, which induced the first episode of immune-mediated thrombotic thrombocytopenic purpura. Results After receiving treatment with plasmapheresis, glucocorticoid medication, rituximab, and other supportive medicines, the patient's physiological circumstances and laboratory indicators improved, and a 4-month follow-up revealed no abnormalities. Conclusion This is a unique case report of an acute hepatitis E-induced immune-mediated thrombotic thrombocytopenic purpura initial episode. This case report offers evidence that hepatitis E virus infection can cause thrombotic thrombocytopenic purpura. In patients with abnormal liver function and thrombocytopenia, we advise screening for hepatitis E or thrombotic thrombocytopenic purpura.
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Affiliation(s)
- Fei Lv
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
- Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China
| | - Yue Zhao
- Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China
| | - Xing-Di Yang
- Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China
| | - Han-Zhu Chen
- Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China
| | - Wen-Ya Ren
- Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China
| | - Ling-Xia Chen
- Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China
| | - Qiao-Qiao Yi
- Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China
| | - Wei Zheng
- Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China
| | - Hong-Ying Pan
- Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China
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Hanno AEF, Khouly EE, Abdel-Rauof M, Moghazy A, Dauod S. Seroprevalence of hepatitis E viral infection among apparently healthy personnels and patients with certain neurological disorders in Alexandria University Hospitals. EGYPTIAN LIVER JOURNAL 2023; 13:30. [DOI: 10.1186/s43066-023-00266-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 06/14/2023] [Indexed: 09/02/2023] Open
Abstract
Abstract
Introduction
Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. There are thought to be 20 million infections per year in poorer nations with inadequate sanitation. In Egypt, awareness about the possible hazards linked to HEV infection is limited due to low socioeconomic and educational levels. Only a small number of sequences have been characterized, making HEV study in Egypt constrained. Numerous factors may have contributed to this neglect. Various extra-hepatic symptoms of HEV infection include neurological problems are recognized. Many European nations have implemented regular HEV monitoring, or targeted screening of blood provided by patients at greater risk to stop the spread of HEV by transfusion.
Aim
Assess the prevalence of HEV infection in asymptomatic blood donors. Increasing awareness about HEV testing in patients with some unexplained neurological disorders.
Methods
Cross-sectional study involving 550 patients: 500 apparently healthy blood donors and 50 patients with some neurological disorders. All subjects were tested for serological markers (IgG and IgM) for HEV using ELISA technique in addition to HEV RNA PCR testing for seropositive patients.
Results
Five hundred asymptomatic blood donors (370 males and 130 females), ages ranging from 20 to 50 years (median 33), 22.6% of them tested positive for HEV (IgG and IgM) of which 2 subjects only had positive HEV RNA PCR testing. In the second group 50 patients (26 males and 24 females) with various unexplained neurological disorders. Liver functions were within normal or showed only a mild increase. Forty-four percent of the patients had positive serology for HEV, with 6 patients testing positive for HEV RNA on PCR.
Conclusion
No need for mass screening for HEV serology among blood donors. HEV infection needs to be considered in patients with unexplained neurological disorders even if the liver functions are not markedly elevated.
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Songtanin B, Molehin AJ, Brittan K, Manatsathit W, Nugent K. Hepatitis E Virus Infections: Epidemiology, Genetic Diversity, and Clinical Considerations. Viruses 2023; 15:1389. [PMID: 37376687 DOI: 10.3390/v15061389] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 06/13/2023] [Accepted: 06/15/2023] [Indexed: 06/29/2023] Open
Abstract
According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are four main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal-oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans via undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection, and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.
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Affiliation(s)
- Busara Songtanin
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Adebayo J Molehin
- Department of Microbiology & Immunology, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA
| | - Kevin Brittan
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Wuttiporn Manatsathit
- Department of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Kenneth Nugent
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
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Takakusagi S, Kakizaki S, Takagi H. The Diagnosis, Pathophysiology, and Treatment of Chronic Hepatitis E Virus Infection-A Condition Affecting Immunocompromised Patients. Microorganisms 2023; 11:1303. [PMID: 37317277 DOI: 10.3390/microorganisms11051303] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 05/01/2023] [Accepted: 05/13/2023] [Indexed: 06/16/2023] Open
Abstract
Hepatitis E is a zoonosis caused by hepatitis E virus (HEV), which was first discovered 40 years ago. Twenty million HEV infections worldwide are estimated each year. Most hepatitis E cases are self-limiting acute hepatitis, but the virus has been recognized to cause chronic hepatitis. Following the first case report of chronic hepatitis E (CHE) in a transplant recipient, CHE has recently been identified as associated with chronic liver damage induced by HEV genotypes 3, 4, and 7-usually in immunocompromised patients such as transplant recipients. In addition, patients infected with HIV and those receiving chemotherapy for malignancy, along with patients with rheumatic disease and COVID-19, have recently been reported as having CHE. CHE can be easily misdiagnosed by usual diagnostic methods of antibody response, such as anti-HEV IgM or IgA, because of the low antibody response in the immunosuppressive condition. HEV RNA should be evaluated in these patients, and appropriate treatments-such as ribavirin-should be given to prevent progression to liver cirrhosis or liver failure. While still rare, cases of CHE in immunocompetent patients have been reported, and care must be taken not to overlook these instances. Herein, we conduct an overview of hepatitis E, including recent research developments and management of CHE, in order to improve our understanding of such cases. The early diagnosis and treatment of CHE should be performed to decrease instances of hepatitis-virus-related deaths around the world.
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Affiliation(s)
- Satoshi Takakusagi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22 Fujioka, Fujioka 375-0024, Gunma, Japan
| | - Satoru Kakizaki
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki 370-0829, Gunma, Japan
| | - Hitoshi Takagi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22 Fujioka, Fujioka 375-0024, Gunma, Japan
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15
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You S, Zhu B, Xin S. Clinical Manifestations of Hepatitis E. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:185-197. [PMID: 37223867 DOI: 10.1007/978-981-99-1304-6_13] [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 clinical manifestations of hepatitis E are similar to those of other types of viral hepatitis. While acute hepatitis E is usually self-limited, pregnant women and chronic liver disease patients suffering from acute hepatitis E usually present with severe clinical manifestations that may develop into fulminant hepatic failure. Chronic HEV infection is typically seen in organ transplant patients; most HEV cases are asymptomatic and rarely display jaundice, fatigue, abdominal pain, fever, fatigue, or ascites. The clinical manifestations of HEV infection in neonates are diverse and have varied clinical signs, biochemistry, and virus-biomarkers. Lastly, the extrahepatic manifestations and complications of hepatitis E are in need of further study.
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Affiliation(s)
- Shaoli You
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Bing Zhu
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shaojie Xin
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
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16
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Peeters M, Schenk J, De Somer T, Roskams T, Locus T, Klamer S, Subissi L, Suin V, Delwaide J, Stärkel P, De Maeght S, Willems P, Colle I, Van Hoof M, Van Acker J, Van Steenkiste C, Moreno C, Janssens F, Reynders M, Steverlynck M, Verlinden W, Lasser L, de Galocsy C, Geerts A, Maus J, Gallant M, Van Outryve S, Marot A, Reynaert H, Decaestecker J, Bottieau E, Schreiber J, Mulkay JP, de Goeij S, Salame M, Dooremont D, Dastis SN, Boes J, Nijs J, Beyls J, Hens N, Nevens F, Van Gucht S, Vanwolleghem T. Viral clade is associated with severity of symptomatic genotype 3 hepatitis E virus infections in Belgium, 2010-2018. J Hepatol 2023; 78:67-77. [PMID: 36075495 DOI: 10.1016/j.jhep.2022.08.033] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 07/29/2022] [Accepted: 08/19/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND & AIMS HEV genotype (gt) 3 infections are prevalent in high-income countries and display a wide spectrum of clinical presentations. Host - but not viral - factors are reported to be associated with worse clinical outcomes. METHODS Demographic, clinical, and biochemical data laboratory-confirmed HEV infections (by PCR and/or a combination of IgM and IgG serology) at the Belgian National Reference Centre between January 2010 and June 2018 were collected using standardised case report forms. Genotyping was based on HEV open reading frame 2 sequences. Serum CXCL10 levels were measured by a magnetic bead-based assay. H&E staining was performed on liver biopsies. RESULTS A total of 274 HEV-infected individuals were included. Subtype assignment was possible for 179/218 viraemic cases, confirming gt3 as dominant with an almost equal representation of clades abchijklm and efg. An increased hospitalisation rate and higher peak serum levels of alanine aminotransferase, bilirubin, and alkaline phosphatase were found in clade efg-infected individuals in univariate analyses. In multivariable analyses, clade efg infections remained more strongly associated with severe disease presentation than any of the previously identified host risk factors, being associated with a 2.1-fold higher risk of hospitalisation (95% CI 1.1-4.4, p = 0.034) and a 68.2% higher peak of bilirubin levels (95% CI 13.3-149.9, p = 0.010), independently of other factors included in the model. In addition, acute clade efg infections were characterised by higher serum CXCL10 levels (p = 0.0005) and a more pronounced liver necro-inflammatory activity (p = 0.022). CONCLUSIONS In symptomatic HEV gt3 infections, clade efg is associated with a more severe disease presentation, higher serum CXCL10 levels, and liver necro-inflammatory activity, irrespective of known host risk factors. CLINICAL TRIAL REGISTRATION The protocol was submitted to clinicaltrials.gov (NCT04670419). IMPACT AND IMPLICATIONS HEV genotype (gt) 3 infections display a wide spectrum of clinical presentations currently ascribed to host factors. Here we examined the role of viral factors on liver disease outcomes by combining viral phylogeny with clinical, biochemical, cytokine, and histological data from 274 Belgian adults infected with HEV presenting between 2010 and 2018. HEV gt 3 clade efg infections were associated with a more severe disease presentation, higher serum CXCL10 levels and liver necro-inflammatory activity, irrespective of known host risk factors. HEV gt3 clade-dependent clinical outcomes call for broad HEV gt3 subtyping in clinical practice and research to help identify those at higher risk for worse outcomes and to further unravel underlying virus-host interactions.
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Affiliation(s)
- Michael Peeters
- Sciensano, Infectious Diseases in Humans, Viral Diseases, National Reference Centre of Hepatitis Viruses, Brussels, Belgium
| | - Julie Schenk
- University of Antwerp, Faculty of Medicine and Health Sciences, Vaccine & Infectious Disease Institute, Centre for Health Economic Research and Modelling Infectious Diseases, Antwerp, Belgium; Hasselt University, Data Science Institute, Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt, Belgium
| | - Thomas De Somer
- University Hospital Antwerp, Gastroenterology & Hepatology, Antwerp, Belgium; Maria Middelares Hospital, Gastroenterology & Hepatology, Ghent, Belgium
| | - Tania Roskams
- KU Leuven, Pathology, Translational Cell and Tissue Research, Leuven, Belgium
| | - Tatjana Locus
- Sciensano, Infectious Diseases in Humans, Viral Diseases, National Reference Centre of Hepatitis Viruses, Brussels, Belgium
| | - Sofieke Klamer
- Sciensano, Epidemiology of Infectious Diseases, Brussels, Belgium
| | - Lorenzo Subissi
- Sciensano, Infectious Diseases in Humans, Viral Diseases, National Reference Centre of Hepatitis Viruses, Brussels, Belgium; European Public Health Microbiology Training Program (EUPHEM), European Centre for Disease Prevention and Control, Stockholm, Sweden
| | - Vanessa Suin
- Sciensano, Infectious Diseases in Humans, Viral Diseases, National Reference Centre of Hepatitis Viruses, Brussels, Belgium
| | - Jean Delwaide
- University Hospital Liege, Gastroenterology & Hepatology, Liege, Belgium
| | - Peter Stärkel
- Cliniques Universitaires Saint-Luc (CUSL), Gastroenterology & Hepatology, Brussels, Belgium
| | | | | | - Isabelle Colle
- A.S.Z. Aalst, Gastroenterology & Hepatology, Aalst, Belgium; Ghent University Hospital, Department of Hepatology and Gastroenterology, Ghent, Belgium
| | - Marc Van Hoof
- Clinique Saint-Luc, Gastroenterology & Hepatology, Bouge, Belgium
| | - Jos Van Acker
- AZ Sint-Lucas, Clinical Microbiology, Ghent, Belgium
| | - Christophe Van Steenkiste
- University Hospital Antwerp, Gastroenterology & Hepatology, Antwerp, Belgium; Maria Middelares Hospital, Gastroenterology & Hepatology, Ghent, Belgium
| | - Christophe Moreno
- CUB Hôpital Erasme, Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Université Libre de Bruxelles, Brussels, Belgium
| | - Filip Janssens
- Jessa Hospital, Gastroenterology & Hepatology, Hasselt, Belgium
| | - Marijke Reynders
- AZ Sint-Jan Brugge-Oostende AV, Medical Microbiology, Laboratory Medicine, Brugge, Belgium
| | | | - Wim Verlinden
- University Hospital Antwerp, Gastroenterology & Hepatology, Antwerp, Belgium; Vitaz, Gastroenterology & Hepatology, Sint-Niklaas, Belgium; University of Antwerp, Laboratory of Experimental Medicine and Pediatrics, Viral Hepatitis Research Group, Antwerp, Belgium
| | - Luc Lasser
- CHU Brugmann, Gastroenterology & Hepatology, Brussels, Belgium
| | | | - Anja Geerts
- Ghent University Hospital, Gastroenterology & Hepatology, Ghent, Belgium
| | - Jeroen Maus
- ZNA Middelheim, Gastroenterology & Hepatology, Antwerp, Belgium
| | - Marie Gallant
- Jan Yperman Ziekenhuis, Gastroenterology & Hepatology, Ieper, Belgium
| | | | - Astrid Marot
- CHU UCL Namur, Université Catholique de Louvain, Department of Gastroenterology and Hepatology, Yvoir, Belgium
| | - Hendrik Reynaert
- University Hospital UZ Brussel, Gastroenterology & Hepatology, Brussels, Belgium
| | | | | | - Jonas Schreiber
- CHIREC Delta Hospital, Gastroenterology & Hepatology, Brussels, Belgium
| | | | | | - Mikhaël Salame
- Centre Hospitalier Régional Haute Senne, Soignies, Belgium
| | | | | | | | - Jochen Nijs
- Sint-Trudo Ziekenhuis, Department of Gastroenterology, Sint-Truiden, Belgium
| | - Jan Beyls
- Sint-Andriesziekenhuis, Department of Gastroenterology, Tielt, Belgium
| | - Niel Hens
- University of Antwerp, Faculty of Medicine and Health Sciences, Vaccine & Infectious Disease Institute, Centre for Health Economic Research and Modelling Infectious Diseases, Antwerp, Belgium; Hasselt University, Data Science Institute, Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt, Belgium
| | - Frederik Nevens
- University Hospitals KU Leuven, Gastroenterology & Hepatology, Leuven, Belgium
| | - Steven Van Gucht
- Sciensano, Infectious Diseases in Humans, Viral Diseases, National Reference Centre of Hepatitis Viruses, Brussels, Belgium.
| | - Thomas Vanwolleghem
- University Hospital Antwerp, Gastroenterology & Hepatology, Antwerp, Belgium; University of Antwerp, Laboratory of Experimental Medicine and Pediatrics, Viral Hepatitis Research Group, Antwerp, Belgium.
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Sayed IM, Karam-Allah Ramadan H, Hafez MHR, Elkhawaga AA, El-Mokhtar MA. Hepatitis E virus (HEV) open reading frame 2: Role in pathogenesis and diagnosis in HEV infections. Rev Med Virol 2022; 32:e2401. [PMID: 36209386 DOI: 10.1002/rmv.2401] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 09/27/2022] [Accepted: 09/28/2022] [Indexed: 11/12/2022]
Abstract
Hepatitis E virus (HEV) infection occurs worldwide. The HEV genome includes three to four open reading frames (ORF1-4). ORF1 proteins are essential for viral replication, while the ORF3 protein is an ion channel involved in the exit of HEV from the infected cells. ORF2 proteins form the viral capsid required for HEV invasion and assembly. They also suppress interferon production and inhibit antibody-mediated neutralisation of HEV, allowing the virus to hijack the host immune response. ORF2 is the only detectable viral protein in the human liver during HEV infection and it is secreted in the plasma, stool, and urine of HEV-infected patients, making it a reliable diagnostic marker. The plasma HEV ORF2 antigen level can predict the outcome of HEV infections. Hence, monitoring HEV ORF2 antigen levels may be useful in assessing the efficacy of anti-HEV therapy. The ORF2 antigen is immunogenic and includes epitopes that can induce neutralising antibodies; therefore, it is a potential HEV vaccine candidate. In this review, we highlighted the different forms of HEV ORF2 protein and their roles in HEV pathogenesis, diagnosis, monitoring the therapeutic efficacy, and vaccine development.
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Affiliation(s)
- Ibrahim M Sayed
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Haidi Karam-Allah Ramadan
- Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Mahmoud H R Hafez
- International Scholar, African Leadership Academy, Johannesburg, South Africa
| | - Amal A Elkhawaga
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Mohamed A El-Mokhtar
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.,Microbiology and Immunology Department, Faculty of Pharmacy, Sphinx University, Assiut, Egypt
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18
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Low platelets: a new and simple prognostic marker for patients with hepatitis E virus-related acute liver failure. Hepatol Int 2022; 16:1116-1126. [PMID: 35229273 DOI: 10.1007/s12072-022-10302-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Accepted: 01/17/2022] [Indexed: 01/27/2023]
Abstract
BACKGROUND AND AIMS Hepatitis E virus-related acute liver failure (HEV-ALF) rapidly worsens and has a high mortality. However, no simple and specific parameters for predicting short-term mortality are available. METHODS A derivation cohort including 97 patients with HEV-ALF and another validation cohort were enrolled. Laboratory and clinical parameters were recorded. Platelet count, model for end-stage liver disease (MELD), and King's College criteria (KCC) were separately used for predicting mortality, and the levels of cytokines associated with systemic inflammation, platelet production, and platelet activation were measured. RESULTS Platelet counts were significantly lower in patients with HEV-ALF, and nonsurvivors had lower platelet counts than survivors (p < 0.001). Platelet count was an independent risk factor for predicting 28- and 90-day mortality in patients with HEV-ALF. The AUROC of the baseline platelet count (cutoff, 131 × 109/L) for 28- and 90-day mortality was 0.786 and 0.764, respectively, which was superior to KCC score (p < 0.05) and comparable to MELD score. Furthermore, the platelet counts at 3 and 7 days after ALF diagnosis had similar predictive power for 28- and 90-day mortality. The value of platelet count was also confirmed in the validation cohort. Moreover, platelet-associated cytokines, including thrombopoietin, platelet factor 4, and P-selectin, were increased in patients with HEV-ALF. CONCLUSIONS Decreased platelet count is a simple and reliable indicator for predicting 28- and 90-day mortality in patients with HEV-ALF. Overactivation of platelets is an important risk for platelet counts decrease, and treatment aiming at platelet count recovery may be considered.
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19
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Kumar KJ, Velamala S, Kumar K, V.G M. Acute Kidney Injury as a Rare Complication of Acute Hepatitis E in a Child; A Case Report. Middle East J Dig Dis 2022; 14:141-144. [PMID: 36619731 PMCID: PMC9489326 DOI: 10.34172/mejdd.2022.268] [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: 11/10/2020] [Accepted: 05/07/2021] [Indexed: 01/11/2023] Open
Abstract
Hepatitis E virus (HEV) infection is a significant public health problem, which infects 20 million individuals every year. The clinical presentation of acute HEV infection is similar to hepatitis A virus (HAV) infection, and few affected children may progress to develop acute liver failure. Extrahepatic manifestations involving other systems have been reported with acute and chronic HEV genotype 3 infections both in adults and children. Herein we report acute kidney injury as a rare complication of acute hepatitis E in a child who recovered with a medical line of management.
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Affiliation(s)
- K. Jagadish Kumar
- Professor of Pediatrics. JSS Medical College, JSS Aademy of Higher Education and Research, Mysore, India,Corresponding Author: K.Jagadish Kumar, MBBS., MD Professor of Pediatrics, JSS Medical College, JSS University, Mysore, India. PIN 570004 Telefax:+9108212335556
| | - Sowmya Velamala
- Resident in Pediatrics, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, India
| | - Krishna Kumar
- Assistant Professor of Pediatrics, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, India
| | - Manjunath V.G
- Professor of Pediatrics, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, India
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Moro O, Suffredini E, Isopi M, Tosti ME, Schembri P, Scavia G. Quantitative Methods for the Prioritization of Foods Implicated in the Transmission of Hepatititis E to Humans in Italy. Foods 2021; 11:foods11010087. [PMID: 35010213 PMCID: PMC8750432 DOI: 10.3390/foods11010087] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 12/09/2021] [Accepted: 12/23/2021] [Indexed: 01/02/2023] Open
Abstract
Hepatitis E is considered an emerging foodborne disease in Europe. Several types of foods are implicated in the transmission of the hepatitis E virus (HEV) to humans, in particular, pork and wild boar products. We developed a parametric stochastic model to estimate the risk of foodborne exposure to HEV in the Italian population and to rank the relevance of pork products with and without liver (PL and PNL, respectively), leafy vegetables, shellfish and raw milk in HEV transmission. Original data on HEV prevalence in different foods were obtained from a recent sampling study conducted in Italy at the retail level. Other data were obtained by publicly available sources and published literature. The model output indicated that the consumption of PNL was associated with the highest number of HEV infections in the population. However, the sensitivity analysis showed that slight variations in the consumption of PL led to an increase in the number of HEV infections much higher than PNL, suggesting that PL at an individual level are the top risky food. Uncertainty analysis underlined that further characterization of the pork products preparation and better assessment of consumption data at a regional level is critical information for fine-tuning the most risky implicated food items in Italy.
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Affiliation(s)
- Ornella Moro
- Department of Food Safety, Nutrition and Veterinary Public Health, National Institute of Health, 00161 Rome, Italy; (E.S.); (G.S.)
- Department of Mathematics, University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy;
- Correspondence:
| | - Elisabetta Suffredini
- Department of Food Safety, Nutrition and Veterinary Public Health, National Institute of Health, 00161 Rome, Italy; (E.S.); (G.S.)
| | - Marco Isopi
- Department of Mathematics, University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy;
| | - Maria Elena Tosti
- National Center for Global Health, National Institute of Health, 00161 Rome, Italy;
| | - Pietro Schembri
- Regional Department for Health Activities and Epidemiological Observatory of the Sicilian Region, 90145 Palermo, Italy;
| | - Gaia Scavia
- Department of Food Safety, Nutrition and Veterinary Public Health, National Institute of Health, 00161 Rome, Italy; (E.S.); (G.S.)
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21
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Lhomme S, Abravanel F, Cintas P, Izopet J. Hepatitis E Virus Infection: Neurological Manifestations and Pathophysiology. Pathogens 2021; 10:pathogens10121582. [PMID: 34959537 PMCID: PMC8705630 DOI: 10.3390/pathogens10121582] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 11/30/2021] [Accepted: 12/01/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) is the first cause of viral hepatitis in the world. While the water-borne HEV genotypes 1 and 2 are found in developing countries, HEV genotypes 3 and 4 are endemic in developed countries due to the existence of animal reservoirs, especially swine. An HEV infection produces many extra-hepatic manifestations in addition to liver symptoms, especially neurological disorders. The most common are neuralgic amyotrophy or Parsonage–Turner syndrome, Guillain–Barré syndrome, myelitis, and encephalitis. The pathophysiology of the neurological injuries due to HEV remains uncertain. The immune response to the virus probably plays a role, but direct virus neurotropism could also contribute to the pathophysiology. This review describes the main neurological manifestations and their possible pathogenic mechanisms.
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Affiliation(s)
- Sébastien Lhomme
- Infinity, Université Toulouse, CNRS, INSERM, UPS, 31300 Toulouse, France; (F.A.); (J.I.)
- Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, 31300 Toulouse, France
- Correspondence: ; Tel.: +33-(0)-5-67-69-04-24
| | - Florence Abravanel
- Infinity, Université Toulouse, CNRS, INSERM, UPS, 31300 Toulouse, France; (F.A.); (J.I.)
- Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, 31300 Toulouse, France
| | - Pascal Cintas
- Service de Neurologie, Hôpital Purpan, CHU Toulouse, 31300 Toulouse, France;
| | - Jacques Izopet
- Infinity, Université Toulouse, CNRS, INSERM, UPS, 31300 Toulouse, France; (F.A.); (J.I.)
- Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, 31300 Toulouse, France
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Wu J, Xiang Z, Zhu C, Yao Y, Bortolanza M, Cao H, Li L. Extrahepatic manifestations related to hepatitis E virus infection and their triggering mechanisms. J Infect 2021; 83:298-305. [PMID: 34324940 DOI: 10.1016/j.jinf.2021.07.021] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Revised: 07/20/2021] [Accepted: 07/22/2021] [Indexed: 02/07/2023]
Abstract
Hepatitis E virus (HEV) infection has many extrahepatic manifestations as well as liver symptoms. Multiple studies have shown that HEV infection has symptoms related to the nervous system, kidneys, cryoglobulinemia, hematological system, reproductive system, autoimmunity and pancreas. Hence, HEV infection should be considered as a systemic disease, rather than solely a liver disease. The extrahepatic manifestations induced by different genotypes of HEV vary. The severity of these diseases does not necessarily correlate with the severity of HEV infection, and even asymptomatic HEV infection may trigger and cause systemic diseases. Patients with systemic manifestations of HEV infection should have priority for antiviral therapy, which could alleviate or improve the extrahepatic manifestations related to HEV infection. However, the extrahepatic manifestations caused by different genotypes of HEV and their corresponding mechanisms have not been clearly identified. This review discusses the extrahepatic manifestations related to HEV infection and their triggering mechanisms.
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Affiliation(s)
- Jian Wu
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China; Department of Clinical Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Rd., Suzhou 215008, China
| | - Ze Xiang
- Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Chunxia Zhu
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China
| | - Yiwen Yao
- Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg 66424, Germany
| | - Mariza Bortolanza
- Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Homburg 66424, Germany
| | - Hongcui Cao
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China; Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases, 79 Qingchun Rd, Hangzhou 310003, China.
| | - Lanjuan Li
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China
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Jafri L, Sajjad A, Saleem S, Jameel H, Kanwar D. Steroid-Responsive Myositis Associated With Acute Hepatitis E Infection. Cureus 2021; 13:e15492. [PMID: 34268024 PMCID: PMC8261785 DOI: 10.7759/cureus.15492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/07/2021] [Indexed: 11/05/2022] Open
Abstract
Acute hepatitis E virus (HEV) infection is usually self-limiting and presents as mild jaundice accompanied by malaise, anorexia, nausea, vomiting, abdominal pain, or fever. Rarely, it can lead to fulminant hepatic failure especially in pregnant women or cause extrahepatic manifestations. We report a case of a young woman already diagnosed with acute HEV infection who presented with a generalized body rash and weakness in all four limbs. She was subsequently diagnosed with inflammatory myositis and treated successfully with steroids. We have reviewed relevant literature for a possible association. Myositis is a rare but known complication of HEV. If timely diagnosed and managed, there is a significant reduction in morbidity.
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Affiliation(s)
- Lubna Jafri
- Neurology, Aga Khan University, Karachi, PAK
| | - Ali Sajjad
- Neurology, Aga Khan University, Karachi, PAK
| | | | - Hira Jameel
- Neurology, Aga Khan University, Karachi, PAK
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24
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Jha AK, Kumar G, Dayal VM, Ranjan A, Suchismita A. Neurological manifestations of hepatitis E virus infection: An overview. World J Gastroenterol 2021; 27:2090-2104. [PMID: 34025066 PMCID: PMC8117739 DOI: 10.3748/wjg.v27.i18.2090] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 02/27/2021] [Accepted: 04/05/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) is an important cause of repeated waterborne outbreaks of acute hepatitis. Recently, several extrahepatic manifestations (EHMs) have been described in patients with HEV infection. Of these, neurological disorders are the most common EHM associated with HEV. The involvement of both the peripheral nervous system and central nervous system can occur together or in isolation. Patients can present with normal liver function tests, which can often be misleading for physicians. There is a paucity of data on HEV-related neurological manifestations; and these data are mostly described as case reports and case series. In this review, we analyzed data of 163 reported cases of HEV-related neurological disorders. The mechanisms of pathogenesis, clinico-demographic profile, and outcomes of the HEV-related neurological disorders are described in this article. Nerve root and plexus disorder were found to be the most commonly reported disease, followed by meningoencephalitis.
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Affiliation(s)
- Ashish Kumar Jha
- Department of Gastroenterology, Indira Gandhi Institute of Medical Sciences, Patna 800014, India
| | - Gaurav Kumar
- Department of Gastroenterology, Indira Gandhi Institute of Medical Sciences, Patna 800014, India
| | - Vishwa Mohan Dayal
- Department of Gastroenterology, Indira Gandhi Institute of Medical Sciences, Patna 800014, India
| | - Abhay Ranjan
- Department of Neurology, Indira Gandhi Institute of Medical Sciences, Patna 800014, India
| | - Arya Suchismita
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, Basant Kunj 110070, New Delhi, India
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25
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Fagan O, Amstrong P, Merwe KVD, Crosnoi D, Steele C, Sopena-Falco J, Parihar V. Viral hepatitis: A brief introduction, review of management, advances and challenges. World J Meta-Anal 2021; 9:139-151. [DOI: 10.13105/wjma.v9.i2.139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/26/2021] [Accepted: 04/23/2021] [Indexed: 02/06/2023] Open
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26
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Pringle R, van Halsema C. Widespread rash as initial presentation of acute hepatitis E in a woman with well-controlled HIV. Int J STD AIDS 2021; 32:671-673. [PMID: 33530880 DOI: 10.1177/0956462420984697] [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: 11/15/2022]
Abstract
Sporadic, acute hepatitis E is increasingly common in the United Kingdom, associated with travel or locally acquired. A 45-year-old woman with well-controlled HIV presented with a widespread, polymorphic rash and transaminitis. Acute genotype 3 hepatitis E infection was confirmed and resolved without intervention. A review of the literature reveals a number of atypical presentations of acute autochthonous hepatitis E. Clinicians should consider testing for hepatitis E in the presence of nonspecific symptoms and deranged liver function tests.
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Affiliation(s)
- Rachel Pringle
- Department of Infectious Diseases and Tropical Medicine, 156778North Manchester General Hospital, Manchester, UK
| | - Clare van Halsema
- Department of Infectious Diseases and Tropical Medicine, 156778North Manchester General Hospital, Manchester, UK
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27
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El-Mokhtar MA, Sayed IM. Model systems for studying extrahepatic pathogenesis of hepatitis E virus. Current knowledge and future directions. Rev Med Virol 2021; 31:e2218. [PMID: 33475223 DOI: 10.1002/rmv.2218] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 01/05/2021] [Indexed: 02/06/2023]
Abstract
Hepatitis E Virus is the most common cause of acute viral hepatitis globally. HEV infection is endemic in developing countries. Also, autochthonous and sporadic cases are reported in developed countries. HEV causes acute and chronic infections. Besides, extrahepatic manifestations including neurological, renal, haematological, acute pancreatitis and complications during pregnancy are associated with HEV infections. The pathogenesis of HEV in the extrahepatic tissues is either due to direct cytopathic effect mediated by the virus replication, or immunological mechanisms caused by an uncontrollable host response. Researchers have used different in vivo and in vitro models to study the pathogenesis of HEV in the extrahepatic tissues and analyse the host immune response against HEV infection. This review highlights the extrahepatic disorders associated with HEV infection. We focused on the in vivo and in vitro models as a tool for elucidating the HEV infection beyond the liver and studying the mechanisms of HEV induced tissue damages.
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Affiliation(s)
- Mohamed A El-Mokhtar
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.,Microbiology and Immunology Department, Faculty of Pharmacy, Sphinx University, Assiut, Egypt
| | - Ibrahim M Sayed
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.,Department of Pathology, School of Medicine, University of California, San Diego La Jolla, California, USA
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28
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Wang CR, Tsai HW. Human hepatitis viruses-associated cutaneous and systemic vasculitis. World J Gastroenterol 2021; 27:19-36. [PMID: 33505148 PMCID: PMC7789062 DOI: 10.3748/wjg.v27.i1.19] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Revised: 12/19/2020] [Accepted: 12/27/2020] [Indexed: 02/06/2023] Open
Abstract
Human hepatitis viruses (HHVs) include hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus, and hepatitis E virus and can cause liver inflammation in their common human host. Usually, HHV is rapidly cleared by the immune system, following acute HHV invasion. The morbidities associated with hepatitis A virus and hepatitis E virus infection occur shortly after their intrusion, in the acute stage. Nevertheless, the viral infectious process can persist for a long period of time, especially in HBV and HCV infection, leading to chronic hepatitis and further progressing to hepatic cirrhosis and liver cancer. HHV infection brings about complications in other organs, and both acute and chronic hepatitis have been associated with clinical presentations outside the liver. Vascular involvement with cutaneous and systemic vasculitis is a well-known extrahepatic presentation; moreover, there is growing evidence for a possible causal relationship between viral pathogens and vasculitis. Except for hepatitis delta virus, other HHVs have participated in the etiopathogenesis of cutaneous and systemic vasculitis via different mechanisms, including direct viral invasion of vascular endothelial cells, immune complex-mediated vessel wall damage, and autoimmune responses with stimulation of autoreactive B-cells and impaired regulatory T-cells. Cryoglobulinemic vasculitis and polyarteritis nodosa are recognized for their association with chronic HHV infection. Although therapeutic guidelines for HHV-associated vasculitis have not yet been established, antiviral therapy should be initiated in HBV and HCV-related systemic vasculitis in addition to the use of corticosteroids. Plasma exchange and/or combined cyclophosphamide and corticosteroid therapy can be considered in patients with severe life-threatening vasculitis manifestations.
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Affiliation(s)
- Chrong-Reen Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan
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29
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Belei O, Ancusa O, Mara A, Olariu L, Amaricai E, Folescu R, Zamfir CL, Gurgus D, Motoc AG, Stânga LC, Strat L, Marginean O. Current Paradigm of Hepatitis E Virus Among Pediatric and Adult Patients. Front Pediatr 2021; 9:721918. [PMID: 34660485 PMCID: PMC8515027 DOI: 10.3389/fped.2021.721918] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 08/31/2021] [Indexed: 12/26/2022] Open
Abstract
Hepatitis E virus (HEV) infection is a polymorphic condition, present throughout the world and involving children and adults. Multiple studies over the last decade have contributed to a better understanding of the natural evolution of this infection in various population groups, several reservoirs and transmission routes being identified. To date, acute or chronic HEV-induced hepatitis has in some cases remained underdiagnosed due to the lower accuracy of serological tests and due to the evolutionary possibility with extrahepatic manifestations. Implementation of diagnostic tests based on nucleic acid analysis has increased the detection rate of this disease. The epidemiological and clinical features of HEV hepatitis differ depending on the geographical areas studied. HEV infection is usually a self-limiting condition in immunocompetent patients, but in certain categories of vulnerable patients it can induce a sudden evolution toward acute liver failure (pregnant women) or chronicity (immunosuppressed patients, post-transplant, hematological, or malignant diseases). In acute HEV infections in most cases supportive treatment is sufficient. In patients who develop chronic hepatitis with HEV, dose reduction of immunosuppressive medication should be the first therapeutic step, especially in patients with transplant. In case of unfavorable response, the initiation of antiviral therapy is recommended. In this review, the authors summarized the essential published data related to the epidemiological, clinical, paraclinical, and therapeutic aspects of HEV infection in adult and pediatric patients.
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Affiliation(s)
- Oana Belei
- First Pediatric Clinic, Disturbance of Growth and Development on Children Research Center, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Oana Ancusa
- Fifth Department of Internal Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Adelina Mara
- Department of Internal Medicine, Emergency City Hospital, Timisoara, Romania
| | - Laura Olariu
- First Pediatric Clinic, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Elena Amaricai
- Department of Rehabilitation Physical Medicine and Rheumatology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Roxana Folescu
- Department of Balneology, Medical Recovery and Rheumatology, Family Discipline, Center for Preventive Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Carmen Lacramioara Zamfir
- Department of Morpho-Functional Sciences I, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Daniela Gurgus
- Department of Balneology, Medical Recovery and Rheumatology, Family Discipline, Center for Preventive Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Andrei G Motoc
- Department of Anatomy and Embriology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Livia Claudia Stânga
- Department of Microbiology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Liliana Strat
- Department of Mother and Child Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Otilia Marginean
- First Pediatric Clinic, Disturbance of Growth and Development on Children Research Center, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
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Mendoza-Lopez C, Lopez-Lopez P, Atienza-Ayala S, Rivero-Juarez A, Benito R. Parsonage-Turner syndrome associated with hepatitis E infection in immunocompetent patients. Virus Res 2020; 290:198165. [PMID: 33007343 DOI: 10.1016/j.virusres.2020.198165] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 09/03/2020] [Accepted: 09/08/2020] [Indexed: 02/08/2023]
Abstract
Introduction The hepatitis E virus (HEV) is the leading cause of acute hepatitis around the world. In recent years, knowledge has increased concerning extrahepatic manifestations caused by HEV, including neurological manifestations such as Parsonage-Turner syndrome (PTS). PTS is characterized by severe shoulder or arm pain and patchy paresis with muscle weakness. The aim of the present study was to assess the association between HEV and PTS. Materials and Methods We reported two cases of PTS associated with HEV, which were diagnosed in a short period of time in the same village. PTS was diagnosed by physical examination and electrophysiological studies, and serology testing for IgM, low-avidity IgG, and RNA of HEV established the diagnosis of acute HEV infection. Results A 44-year-old man who presented cervicobrachial pain accompanied by paresthesia, dyspnea, and isolated derangement of liver enzymes and 57-year-old women with cervical pain radiated to upper limbs, paresthesia, and liver cytolysis, although, this patient was initially diagnosed as having drug-induced hepatitis. Finally, the diagnosis was Parsonage- Turner syndrome associated with hepatitis e virus. In both patients, symptoms were bilateral and they required hospital admission. Both consumed vegetables are grown in a local patch and the phylogenetic analysis showed genotype 3f. Then, we reviewed the literature on PTS and HEV and we found 62 previously described cases that were more likely to be men (86.20 %) with more frequent bilateral symptoms (85.71 %). Genotype 3 is the most commonly associated. Three of those cases were diagnosed in Spain. Conclusions According to our findings, HEV should be considered in patients with neuralgic amyotrophy, including those with the absence of liver cytolysis.
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Affiliation(s)
- Claudia Mendoza-Lopez
- Microbiology Department, University Clinical Lozano Blesa Hospital, Zaragoza, Spain.
| | - Pedro Lopez-Lopez
- Infectious Diseases Unit, Clinical Virology and Zoonoses Unit, Maimonides Institute for Biomedical Research, Reina Sofia Hospital, University of Cordoba, Cordoba, Spain
| | - Saida Atienza-Ayala
- Neurology Department, University Clinical Lozano Blesa Hospital, Zaragoza, Spain
| | - Antonio Rivero-Juarez
- Infectious Diseases Unit, Clinical Virology and Zoonoses Unit, Maimonides Institute for Biomedical Research, Reina Sofia Hospital, University of Cordoba, Cordoba, Spain
| | - Rafael Benito
- Microbiology Department, University Clinical Lozano Blesa Hospital, Zaragoza, Spain
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31
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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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Wallace SJ, Swann R, Donnelly M, Kemp L, Guaci J, Murray A, Spoor J, Lin N, Miller M, Dalton HR, Hussaini SH, Gunson R, Simpson K, Stanley A, Fraser A. Mortality and morbidity of locally acquired hepatitis E in the national Scottish cohort: a multicentre retrospective study. Aliment Pharmacol Ther 2020; 51:974-986. [PMID: 32285976 DOI: 10.1111/apt.15704] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 11/19/2019] [Accepted: 03/09/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND Hepatitis E virus (HEV) is the most common acute viral hepatitis in Scotland. Little is known about the burden of morbidity and mortality, which can be high in chronic liver disease or immunocompromised states. AIMS To record the morbidity and mortality of HEV in Scotland. METHODS Demographic, clinical and laboratory data were collected retrospectively from all cases of HEV reported to virology departments across nine NHS health boards, between January 2013 and January 2018. RESULTS Five hundred and eleven cases were included (Mean age 62, 64% male). 58 (11%) cases had pre-existing cirrhosis and 110 (21%) had diabetes. Three hundred and three patients required admission (59%), totalling 2747 inpatient bed days. Seventeen (3.3%) HEV-related deaths were recorded. Factors that predicted mortality included haematological malignancy (OR 51.56, 95% CI 3.40-782.83, P = 0.005), cirrhosis (OR 41.85, 95% CI 2.85-594.16, P = 0.006), higher serum bilirubin (OR 1.01, 95% CI 1.01-1.02, P = 0.011) and chronic HEV infection (OR 0.02, 95% CI 0.02-0.28, P < 0.001). HEV infection affected 35 transplant patients of 106 total immunosuppressed patients (21%). Of these, 25 patients received Ribavirin therapy with a sustained virological remission of 76%. Thirty-five (6.7%) patients developed acute or acute-on-chronic liver failure with two requiring transplant. Thirty-seven (7.2%) patients reported neurological complications with 10 developing neuralgic amyotrophy, 6 Guillain-Barré and 2 encephalitis. Forty-four (8.6%) patients developed acute kidney injury. CONCLUSION In Scotland, HEV causes a significant burden of inpatient admissions, organ failure and death. Cirrhosis and haematological malignancy are significant predictors of mortality. Neurological and renal complications occur in a significant minority.
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Affiliation(s)
| | - Rachael Swann
- Department of Gastroenterology, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Mhairi Donnelly
- Department of Gastroenterology, Royal Infirmary Edinburgh, Edinburgh, UK
| | - Linda Kemp
- Department of Gastroenterology, Ninewells Hospital, Dundee, UK
| | - Julia Guaci
- Department of Gastroenterology, Royal Infirmary Edinburgh, Edinburgh, UK
| | - Aimee Murray
- Department of Gastroenterology, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Johannes Spoor
- Department of Gastroenterology, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Nan Lin
- Department of Mathematics, Physics and Electrical Engineering, Northumbria University, Newcastle, UK
| | - Michael Miller
- Department of Gastroenterology, Ninewells Hospital, Dundee, UK
| | - Harry R Dalton
- Department of Gastroenterology, Royal Cornwall Hospital Trust, Truro, Cornwall, UK
| | - S Hyder Hussaini
- Department of Gastroenterology, Royal Cornwall Hospital Trust, Truro, Cornwall, UK
| | - Rory Gunson
- Department of Virology, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Kenneth Simpson
- Department of Gastroenterology, Royal Infirmary Edinburgh, Edinburgh, UK
| | - Adrian Stanley
- Department of Gastroenterology, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Andrew Fraser
- Department of Gastroenterology, NHS Greater Glasgow and Clyde, Glasgow, UK.,Department of Gastroenterology, Royal Infirmary Edinburgh, Edinburgh, UK
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Tarantino G, Ortolani A, Marinelli K, Benedetti A, Marconi G, Calzolari M, Dalton HR, Marzioni M, Schiadà L, Fava G, Chiodera A, Amadio G, Fiorentini A, Riva A, Fraticelli P, Menzo S, Bagnarelli P. Locally acquired hepatitis E virus in Marche Italy: Clinical/laboratory features and outcome. Dig Liver Dis 2020; 52:434-439. [PMID: 31874836 DOI: 10.1016/j.dld.2019.11.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 10/23/2019] [Accepted: 11/18/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Hepatitis E Virus is endemic in Europe with increasing numbers of cases in recent years, also in Italy where this phenomenon has hitherto been modest. The aim of this study was to document the clinical features/natural history of locally acquired hepatitis E in our territory and explore factors which determine adverse outcome. METHODS Retrospective study of patients with locally-acquired HEV (hepatitis E virus) in Marche, Italy (2011-2019). RESULTS 1189 patients were tested for HEV with 89 confirmed cases. 81 (6.8%) had locally acquired infection; 54 (66%) were male (mean age 55.5 years) and 32 (39.5%) had active co-morbidities. 41 cases were viraemic (all HEV-3 (HEV genotype 1,2,3,4)); acute infection was found in 79 and chronic infection in 2. Forty-five cases (55%) required admission to hospital, for a total of 785 days. 4 patients developed acute on-chronic liver failure, 6 developed acute kidney injury and 8 died: all had active comorbidities. Univariate analysis showed that bilirubin, INR, immunosuppression, cirrhosis and diabetes were associated with death. On multivariant analysis the only predictor of death was the presence of diabetes (p = 0.04). CONCLUSIONS Hepatitis E in Marche Italy is mostly locally acquired and caused by HEV-3 that impacts on the morbidity and mortality particularly for fragile patients.
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Affiliation(s)
- Giuseppe Tarantino
- Department of Gastroenterology and Transplants, Clinic of Gastroenterology, Hospital of Ancona, Università Politecnica delle Marche, Italy.
| | - Alessio Ortolani
- Department of Gastroenterology and Transplants, Clinic of Gastroenterology, Hospital of Ancona, Università Politecnica delle Marche, Italy
| | - Katia Marinelli
- Department of Biomedical Sciences and Public Health, Virology, Hospital of Ancona, Università Politecnica delle Marche, Italy
| | - Antonio Benedetti
- Department of Gastroenterology and Transplants, Clinic of Gastroenterology, Hospital of Ancona, Università Politecnica delle Marche, Italy
| | - Giulia Marconi
- Department of Gastroenterology and Transplants, Clinic of Gastroenterology, Hospital of Ancona, Università Politecnica delle Marche, Italy
| | - Manuela Calzolari
- Department of Gastroenterology and Transplants, Clinic of Gastroenterology, Hospital of Ancona, Università Politecnica delle Marche, Italy
| | | | - Marco Marzioni
- Department of Gastroenterology and Transplants, Clinic of Gastroenterology, Hospital of Ancona, Università Politecnica delle Marche, Italy
| | - Laura Schiadà
- Department of Gastroenterology and Transplants, Clinic of Gastroenterology, Hospital of Ancona, Università Politecnica delle Marche, Italy
| | - Giammarco Fava
- Department of Gastroenterology and Transplants, Clinic of Gastroenterology, Hospital of Ancona, Università Politecnica delle Marche, Italy
| | | | | | - Alessandro Fiorentini
- Units of Infective diseases Hospital of Ancona, Università Politecnica delle Marche, Italy
| | - Alessandra Riva
- Units of Infective diseases Hospital of Ancona, Università Politecnica delle Marche, Italy
| | - Paolo Fraticelli
- Department of Internal Medicine, Unit of Medical Clinic, Hospital of Ancona, Università Politecnica delle Marche, Italy
| | - Stefano Menzo
- Department of Biomedical Sciences and Public Health, Virology, Hospital of Ancona, Università Politecnica delle Marche, Italy
| | - Patrizia Bagnarelli
- Department of Biomedical Sciences and Public Health, Virology, Hospital of Ancona, Università Politecnica delle Marche, Italy
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Mrzljak A, Novak R, Pandak N, Tabain I, Franusic L, Barbic L, Bogdanic M, Savic V, Mikulic D, Pavicic-Saric J, Stevanovic V, Vilibic-Cavlek T. Emerging and neglected zoonoses in transplant population. World J Transplant 2020; 10:47-63. [PMID: 32257849 PMCID: PMC7109593 DOI: 10.5500/wjt.v10.i3.47] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Revised: 03/15/2020] [Accepted: 03/22/2020] [Indexed: 02/06/2023] Open
Abstract
Zoonoses represent a problem of rising importance in the transplant population. A close relationship and changes between human, animal and environmental health ("One Health" concept) significantly influence the transmission and distribution of zoonotic diseases. The aim of this manuscript is to perform a narrative review of the published literature on emerging and neglected zoonoses in the transplant population. Many reports on donor-derived or naturally acquired (re-)emerging arboviral infections such as dengue, chikungunya, West Nile, tick-borne encephalitis and Zika virus infection have demonstrated atypical or more complicated clinical course in immunocompromised hosts. Hepatitis E virus has emerged as a serious problem after solid organ transplantation (SOT), leading to diverse extrahepatic manifestations and chronic hepatitis with unfavorable outcomes. Some neglected pathogens such as lymphocytic choriomeningitis virus can cause severe infection with multi-organ failure and high mortality. In addition, ehrlichiosis may be more severe with higher case-fatality rates in SOT recipients. Some unusual or severe presentations of borreliosis, anaplasmosis and rickettsioses were also reported among transplant patients. Moreover, toxoplasmosis as infectious complication is a well-recognized zoonosis in this population. Although rabies transmission through SOT transplantation has rarely been reported, it has become a notable problem in some countries. Since the spreading trends of zoonoses are likely to continue, the awareness, recognition and treatment of zoonotic infections among transplant professionals should be imperative.
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Affiliation(s)
- Anna Mrzljak
- Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Rafaela Novak
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Nenad Pandak
- Depatment of Medicine, The Royal Hospital Muscat, Muscat 111, Oman
| | - Irena Tabain
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | | | - Ljubo Barbic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Maja Bogdanic
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | - Vladimir Savic
- Poultry Center, Croatian Veterinary Institute, Zagreb 10000, Croatia
| | - Danko Mikulic
- Department of Abdominal and Transplant Surgery, Merkur University Hospital, Zagreb 10000, Croatia
| | - Jadranka Pavicic-Saric
- Department of Anesthesiology and Intensive Medicine, Merkur University Hospital, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Vladimir Stevanovic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Tatjana Vilibic-Cavlek
- Department of Virology, Croatian Institute of Public Health; School of Medicine, University of Zagreb, Zagreb 10000, Croatia
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Rawla P, Raj JP, Kannemkuzhiyil AJ, Aluru JS, Thandra KC, Gajendran M. A Systematic Review of the Extra-Hepatic Manifestations of Hepatitis E Virus Infection. Med Sci (Basel) 2020; 8:E9. [PMID: 32033102 PMCID: PMC7151617 DOI: 10.3390/medsci8010009] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Revised: 01/30/2020] [Accepted: 01/30/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) is a non-enveloped, positive-sense, single-stranded RNA icosahedral virus belongs to the genus Orthohepevirus within the Hepeviridae family. HEV infection can be asymptomatic, or it can cause icteric or fulminant hepatitis. Off late, there have been a number of publications reporting the extra-hepatic manifestations of HEV infection, and this systematic review is aimed at summarizing the available evidence in this regard. Two independent investigators searched PubMed, PubMed Central and Embase databases using the search string "(((hepatitis E) AND (Extrahepatic OR Extra-Hepatic))) OR ((Hepatitis E) AND (Neurology OR Cardiology OR Respiratory OR Lung OR Gastrointestinal OR musculoskeletal OR immunology OR pulmonary)) Filters: Abstract availability, English language, and Human studies". The extra-hepatic manifestations reported in each of the selected articles were classified and reported as neurological, cardiovascular, and hematological and miscellaneous manifestations. The total number of various manifestations reported in our study were n = 324. These include neurological manifestations (n = 178/324 (54.94%)), cardiovascular and hematological manifestations (n = 113/324 (34.88%)), gastro-intestinal/pancreaticobiliary manifestations (n = 24/324 (7.41%)) and other rarer manifestations involving systems such as renal (n = 4/324; 1.24%), endocrine (n = 1/324; 0.31%), dermatology (n = 1/324; 0.31%), respiratory (n = 1/324; 0.31%), muscular (n = 1/324; 0.31%) and immune system (n = 1/324; 0.31%). Thus, HEV can have extra-hepatic manifestations affecting any system of the human body. Further research is needed to elucidate the underlying pathophysiological manifestations of these extra-hepatic manifestations and to prove causal association with HEV.
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Affiliation(s)
- Prashanth Rawla
- Department of Medicine, Sovah Health, Martinsville, VA 24112, USA
| | - Jeffrey Pradeep Raj
- Department of Clinical Pharmacology, Seth G.S. Medical College & King Edward Memorial Hospital, Mumbai 400012, India;
| | - Alan Jose Kannemkuzhiyil
- St. Johns Medical College, St. John’s National Academy of Health Sciences, Bengaluru, Karnataka 560034, India;
| | - John Sukumar Aluru
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02212, USA;
| | - Krishna Chaitanya Thandra
- Department of Pulmonary and Critical Care Medicine, Sentara Virginia Beach General Hospital, Virginia Beach, VA 23454, USA;
| | - Mahesh Gajendran
- Department of Internal Medicine, Texas Tech University Health Sciences Center El Paso, Paul L. Foster School of Medicine, El Paso, TX 79905, USA;
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Lhomme S, Marion O, Abravanel F, Izopet J, Kamar N. Clinical Manifestations, Pathogenesis and Treatment of Hepatitis E Virus Infections. J Clin Med 2020; 9:E331. [PMID: 31991629 PMCID: PMC7073673 DOI: 10.3390/jcm9020331] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 01/14/2020] [Accepted: 01/22/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis throughout the world. Most infections are acute but they can become chronic in immunocompromised patients, such as solid organ transplant patients, patients with hematologic malignancy undergoing chemotherapy and those with a human immunodeficiency virus (HIV) infection. Extra-hepatic manifestations, especially neurological and renal diseases, have also been described. To date, four main genotypes of HEV (HEV1-4) were described. HEV1 and HEV2 only infect humans, while HEV3 and HEV4 can infect both humans and animals, like pigs, wild boar, deer and rabbits. The real epidemiology of HEV has been underestimated because most infections are asymptomatic. This review focuses on the recent advances in our understanding of the pathophysiology of acute HEV infections, including severe hepatitis in patients with pre-existing liver disease and pregnant women. It also examines the mechanisms leading to chronic infection in immunocompromised patients and extra-hepatic manifestations. Acute infections are usually self-limiting and do not require antiviral treatment. Conversely, a chronic HEV infection can be cleared by decreasing the dose of immunosuppressive drugs or by treating with ribavirin for 3 months. Nevertheless, new drugs are needed for those cases in which ribavirin treatment fails.
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Affiliation(s)
- Sébastien Lhomme
- Virology Laboratory, National Reference Center for Hepatitis E Virus, Toulouse Purpan University Hospital, 31300 Toulouse, France; (F.A.); (J.I.)
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
| | - Olivier Marion
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
- Department of Nephrology and Organs Transplantation, Toulouse Rangueil University Hospital, 31400 Toulouse, France
| | - Florence Abravanel
- Virology Laboratory, National Reference Center for Hepatitis E Virus, Toulouse Purpan University Hospital, 31300 Toulouse, France; (F.A.); (J.I.)
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
| | - Jacques Izopet
- Virology Laboratory, National Reference Center for Hepatitis E Virus, Toulouse Purpan University Hospital, 31300 Toulouse, France; (F.A.); (J.I.)
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
| | - Nassim Kamar
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
- Department of Nephrology and Organs Transplantation, Toulouse Rangueil University Hospital, 31400 Toulouse, France
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Liu H, Ma Y. Hepatitis E virus-associated Guillain-Barre syndrome: Revision of the literature. Brain Behav 2020; 10:e01496. [PMID: 31828968 PMCID: PMC6955827 DOI: 10.1002/brb3.1496] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 11/12/2019] [Accepted: 11/16/2019] [Indexed: 12/18/2022] Open
Abstract
INTRODUCTION The association between preceding infection of hepatitis E virus (HEV) and Guillain-Barre syndrome (GBS) has been found for more than a decade, while hepatitis E virus-associated Guillain-Barre syndrome (HEV-associated GBS) still remains poorly understood. Initially discovered in 2000, the association between GBS and HEV has been focused by neurologists increasingly. Five percent of patients with GBS had preceding acute HEV infection in the Netherlands and higher rate was found in Bangladesh (11%) where HEV is endemic. METHOD An extensive review of relevant literature was undertaken. RESULTS Hepatitis E virus infection may induce GBS via direct viral damage according to recent research findings. On the other hand, the presence of antiganglioside GM1 or GM2 antibodies in serum of some HEV-associated GBS patients indicates that HEV infection may trigger GBS by activating autoimmune response to destroy myelin or axon mistakenly. Management of HEV-associated GBS has no obvious difference from GBS. It mainly consists of supportive therapy and immunotherapy. Intravenous immunoglobulin (IVIG) or plasma exchange (PLEX) was used in most reported cases, which is the main strategy for clinical treatment of HEV-associated GBS. Whether antiviral therapy could be additional strategy other than the routine therapy to shorten the length of disease course is one of the most urgent problems and requires further study. CONCLUSIONS An overview of possible pathogenesis will gain a first insight into why HEV, traditionally recognized as only hepatotropic, can induce many neurological disorders represented by GBS. Moreover, understanding of the underlying mechanisms may contribute to development of a novel therapeutic strategy. This review also summarizes management and clinical characteristics of HEV-associated GBS, aiming to achieve early recognition and good recovery.
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Affiliation(s)
- Hang Liu
- Department of NeurologyShengjing HospitalChina Medical UniversityShenyangChina
| | - Ying Ma
- Department of NeurologyShengjing HospitalChina Medical UniversityShenyangChina
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Ripellino P, Pasi E, Melli G, Staedler C, Fraga M, Moradpour D, Sahli R, Aubert V, Martinetti G, Bihl F, Bernasconi E, Terziroli Beretta-Piccoli B, Cerny A, Dalton HR, Zehnder C, Mathis B, Zecca C, Disanto G, Kaelin-Lang A, Gobbi C. Neurologic complications of acute hepatitis E virus infection. NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION 2019; 7:7/1/e643. [PMID: 31806684 PMCID: PMC6935854 DOI: 10.1212/nxi.0000000000000643] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 10/11/2019] [Indexed: 02/06/2023]
Abstract
Objective To assess the prevalence and clinical features of neurologic involvement in patients with acute hepatitis E virus (HEV) infection in Southern Switzerland. Methods Among 1,940 consecutive patients investigated for acute hepatitis E, we identified 141 cases of acute of HEV infection (anti-HEV immunoglobulin M and immunoglobulin G both reactive and/or HEV RNA positive) between June 2014 and September 2017. Neurologic cases were followed up for 6 months. We compared patients with and without neurologic symptoms. Results Neurologic symptoms occurred in 43 acute HEV cases (30.4%) and consisted of neuralgic amyotrophy (NA, n = 15, 10.6%) and myalgia (n = 28, 19.8%). All NA cases were immunocompetent. Men had higher odds (OR = 5.2, CI 1.12–24.0, p = 0.03) of developing NA after infection with HEV, and in 3 couples simultaneously infected with HEV, only men developed NA. Bilateral involvement of NA was predominant (2:1) and occurred only in men. Seven NA cases were viremic (all genotype 3), but HEV was undetectable in their CSF. In the acute phase of NA, 9 patients were treated with intravenous immunoglobulin and 4 with prednisone, reporting no side effects and improvement in pain and strength. Myalgia occurred both without (n = 16) or with (n = 12) concomitant elevated serum creatinine kinase. Seven cases with myalgia in the shoulder girdle did not have muscle weakness (“forme fruste” of NA). Conclusions Neurologic symptoms occurred in one-third of acute HEV infections and consisted of NA and myalgia. NA seems to occur more frequently in men infected by HEV and has a predominant (but not exclusive) bilateral involvement.
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Affiliation(s)
- Paolo Ripellino
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
| | - Emanuela Pasi
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Giorgia Melli
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Claudio Staedler
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Monserrat Fraga
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Darius Moradpour
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Roland Sahli
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Vincent Aubert
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Gladys Martinetti
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Florian Bihl
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Enos Bernasconi
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Benedetta Terziroli Beretta-Piccoli
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Andreas Cerny
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Harry Roland Dalton
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Cinzia Zehnder
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Barbara Mathis
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Chiara Zecca
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Giulio Disanto
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Alain Kaelin-Lang
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
| | - Claudio Gobbi
- From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH
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Fousekis FS, Mitselos IV, Christodoulou DK. Extrahepatic manifestations of hepatitis E virus: An overview. Clin Mol Hepatol 2019; 26:16-23. [PMID: 31601068 PMCID: PMC6940480 DOI: 10.3350/cmh.2019.0082] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 09/16/2019] [Indexed: 12/14/2022] Open
Abstract
Hepatitis E virus (HEV) is a significant health problem with approximately 20 million individuals infected annually. HEV infection has been associated with a wide spectrum of extrahepatic manifestations, including neurological, hematological and renal disorders. Guillain-Barré syndrome and neuralgic amyotrophy are the most frequent neurological manifestations. In addition, HEV infection has been observed with other neurological diseases, such as encephalitis, myelitis and Bell’s palsy. Hematologic manifestations include anemia due to glucose-6-phospate dehydrogonase deficiency, autoimmune hemolytic anemia and severe thrombocytopenia. Membranoproliferative glomerulonephritis and relapse IgA nephropathy with or without coexisting cryoglobulinemia appear to be the most common renal injuries related with HEV infection. Also, HEV infection has been associated with acute pancreatitis and other immune-mediated manifestations, such as arthritis and myocarditis. However, the pathophysiologic mechanisms of HEV-related extrahepatic manifestations are still largely unclear.
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Affiliation(s)
- Fotios S Fousekis
- Department of Gastroenterology and Hepatology, University Hospital of Ioannina, School of Health Sciences, University of Ioannina, Ioannina, Greece
| | - Ioannis V Mitselos
- Department of Gastroenterology and Hepatology, University Hospital of Ioannina, School of Health Sciences, University of Ioannina, Ioannina, Greece
| | - Dimitrios K Christodoulou
- Department of Gastroenterology and Hepatology, University Hospital of Ioannina, School of Health Sciences, University of Ioannina, Ioannina, Greece
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Sayed IM, Elkhawaga AA, El-Mokhtar MA. In vivo models for studying Hepatitis E virus infection; Updates and applications. Virus Res 2019; 274:197765. [PMID: 31563457 DOI: 10.1016/j.virusres.2019.197765] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 09/17/2019] [Accepted: 09/20/2019] [Indexed: 02/08/2023]
Abstract
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis globally. HEV belongs to the Hepeviridae family and at least five genotypes (gt) infect humans. Several animal species are reservoirs for different HEV strains, and they are the source of infection for humans. Some HEV strains are species specific, but other strains could cross species and infect many hosts. The study of HEV infection and pathogenesis was hampered due to the lack of an in vitro and in vivo robust model system. The cell culture system has been established for certain HEV strains, especially gt3 and 4, but gt1 strains replicate poorly in vitro. To date, animal models are the best tool for studying HEV infection. Non-human primates (NHPs) and pigs are the main animal models used for studying HEV infection, but ethical and financial concerns restrict the use of NHPs in research. Therefore, new small animal models have been developed which help more progress in HEV research. In this review, we give updates on the animal models used for studying HEV infection, focusing on the applicability of each model in studying different HEV infections, cross-species infection, virus-host interaction, evaluation of anti-HEV therapies and testing potential HEV vaccines.
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Affiliation(s)
- Ibrahim M Sayed
- Department of Pathology, School of Medicine, University of California, San Diego, La Jolla, California, USA; Medical Microbiology and Immunology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
| | - Amal A Elkhawaga
- Medical Microbiology and Immunology Department, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Mohamed A El-Mokhtar
- Medical Microbiology and Immunology Department, Faculty of Medicine, Assiut University, Assiut, Egypt
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Heo NY. [Hepatitis E Virus: Epidemiology, Diagnosis, and Management]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2019; 74:130-136. [PMID: 31554028 DOI: 10.4166/kjg.2019.74.3.130] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 08/27/2019] [Accepted: 08/28/2019] [Indexed: 01/08/2023]
Abstract
The HEV is a known cause of water-borne outbreaks of acute non-A non-B hepatitis in developing countries, which affects young people and may result in high mortality in pregnant women. In recent decades, however, HEV genotypes 3 and 4 have been known as a cause of sporadic zoonotic infections in older males from swine HEV worldwide. Most acute HEV infections are self-limited. On the other hand, in immunosuppressed patients, including solid organ transplant recipients, chronic HEV infections may exist and progress to liver cirrhosis or decompensation. Therefore, physicians need to recognize HEV as a major pathogen for acute and chronic hepatitis of unknown causes and investigate this disease.
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Affiliation(s)
- Nae-Yun Heo
- Division of Gastroenterology, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
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Meyyur Aravamudan V, Khan SR, Dosala S, Hussain I. Beyond the Liver, Hepatitis E Can Affect the Nerves, Pancreas, and Blood Vessels. Extrahepatic Manifestations of Hepatitis E: A Comprehensive Literature Review. Cureus 2019; 11:e5499. [PMID: 31667034 PMCID: PMC6816525 DOI: 10.7759/cureus.5499] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Extrahepatic manifestations of Hepatitis E, though rare, are being increasingly reported in the medical literature. In this review article, we will discuss the extrahepatic manifestations of hepatitis E, such as Guillain-Barre syndrome, pancreatitis, and cryoglobulinemia, their clinical association with hepatitis E, and their management.
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Affiliation(s)
| | - Shahab R Khan
- Internal Medicine, Banner University Medical Center, University of Arizona, Tucson, USA
| | - Sushanth Dosala
- Internal Medicine, University of Illinois at Chicago, Illinois, USA
| | - Ikram Hussain
- Internal Medicine: Gastroenterology, Woodlands Health Campus, Singapore, SGP
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Dumas M, Corre F, Payancé A, Guedj N, Durand F, Descamps V, Le Bozec P. [Eruptive disseminated superficial porokeratosis associated with acute hepatitis E]. Ann Dermatol Venereol 2019; 146:655-658. [PMID: 31326131 DOI: 10.1016/j.annder.2019.05.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2018] [Revised: 12/06/2018] [Accepted: 05/15/2019] [Indexed: 11/28/2022]
Abstract
BACKGROUND Porokeratosis (PK) is a rare form of dermatosis characterized by a keratinization disorder of unknown etiology. Herein we describe the first case associated with hepatitis E virus infection. PATIENTS AND METHODS A 69-year-old patient with colorectal cancer treated with radiation and chemotherapy followed by surgery in April 2017 presented two months later with jaundice associated with annular keratotic lesions of the skin with a raised border. Blood tests revealed elevated liver enzymes and hyperbilirubinemia. Viral hepatitis E was diagnosed based on serology and viral PCR after other aetiologies such as obstruction, auto-immune disease and other viruses (HAV, HBV, HCV, HSV, HIV, EBV and CMV) had been ruled out. A skin biopsy showed a cornoid lamella. Disseminated superficial porokeratosis associated with hepatitis E infection was then diagnosed. DISCUSSION The mechanism of PK is unknown and probably involves a combination of different factors. PK has been described in patients with treatment-induced immunosuppression, solid cancer or AIDS, sometimes promoted by HCV viral infection, but never with concomitant HEV infection. A combination of immunosuppression induced by radio-chemotherapy and HEV infection could have prompted the development of PK in our patient. CONCLUSION We report the first case of eruptive disseminated superficial porokeratosis associated with hepatitis E infection. The exact role of hepatitis E infection in the development of PK is still unclear.
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Affiliation(s)
- M Dumas
- Unité de dermatologie, hôpitaux universitaires Paris Nord Val-de-Seine (HUPNVS), hôpital Beaujon, 92110 Clichy, France.
| | - F Corre
- Service d'hépatologie, HUPNVS, hôpital Beaujon, 92110 Clichy, France
| | - A Payancé
- Service d'hépatologie, HUPNVS, hôpital Beaujon, 92110 Clichy, France
| | - N Guedj
- Service d'anatomopathologie, HUPNVS, hôpital Beaujon, 92110 Clichy, France
| | - F Durand
- Service d'hépatologie, HUPNVS, hôpital Beaujon, 92110 Clichy, France
| | - V Descamps
- Service de dermatologie, HUPNVS, hôpital Bichat, 75018 Paris, France
| | - P Le Bozec
- Unité de dermatologie, hôpitaux universitaires Paris Nord Val-de-Seine (HUPNVS), hôpital Beaujon, 92110 Clichy, France
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Horvatits T, Schulze Zur Wiesch J, Lütgehetmann M, Lohse AW, Pischke S. The Clinical Perspective on Hepatitis E. Viruses 2019; 11:E617. [PMID: 31284447 PMCID: PMC6669652 DOI: 10.3390/v11070617] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 06/26/2019] [Accepted: 07/03/2019] [Indexed: 12/17/2022] Open
Abstract
Every year, there are an estimated 20 million hepatitis E virus (HEV) infections worldwide, leading to an estimated 3.3 million symptomatic cases of hepatitis E. HEV is largely circulating in the west and is associated with several hepatic and extrahepatic diseases. HEV Genotype 1 and 2 infections are waterborne and causative for epidemics in the tropics, while genotype 3 and 4 infections are zoonotic diseases and are mainly transmitted by ingestion of undercooked pork in industrialized nations. The clinical course of these infections differs: genotype 1 and 2 infection can cause acute illness and can lead to acute liver failure (ALF) or acute on chronic liver failure (ACLF) with a high mortality rate of 20% in pregnant women. In contrast, the majority of HEV GT-3 and -4 infections have a clinically asymptomatic course and only rarely lead to acute on chronic liver failure in elderly or patients with underlying liver disease. Immunosuppressed individuals infected with genotype 3 or 4 may develop chronic hepatitis E, which then can lead to life-threatening cirrhosis. Furthermore, several extra-hepatic manifestations affecting various organs have been associated with ongoing or previous HEV infections but the causal link for many of them still needs to be proven. There is no approved specific therapy for the treatment of acute or chronic HEV GT-3 or -4 infections but off-label use of ribavirin has been demonstrated to be safe and effective in the majority of patients. However, in approximately 15% of chronically HEV infected patients, cure is not possible.
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Affiliation(s)
- Thomas Horvatits
- Department of Medicine, University Medical Center Hamburg-Eppendorf, 22527 Hamburg, Germany
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner sites, 22527 Hamburg, Germany
| | - Julian Schulze Zur Wiesch
- Department of Medicine, University Medical Center Hamburg-Eppendorf, 22527 Hamburg, Germany
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner sites, 22527 Hamburg, Germany
| | - Marc Lütgehetmann
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner sites, 22527 Hamburg, Germany
- Institute of Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, 22527 Hamburg, Germany
| | - Ansgar W Lohse
- Department of Medicine, University Medical Center Hamburg-Eppendorf, 22527 Hamburg, Germany
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner sites, 22527 Hamburg, Germany
| | - Sven Pischke
- Department of Medicine, University Medical Center Hamburg-Eppendorf, 22527 Hamburg, Germany.
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel and Heidelberg Partner sites, 22527 Hamburg, Germany.
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Aggarwal R, Goel A. Natural History, Clinical Manifestations, and Pathogenesis of Hepatitis E Virus Genotype 1 and 2 Infections. Cold Spring Harb Perspect Med 2019; 9:a032136. [PMID: 29735580 PMCID: PMC6601454 DOI: 10.1101/cshperspect.a032136] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Infection with genotype 1 or 2 hepatitis E virus (HEV) results primarily from human-to-human transmission through the fecal-oral route in low-resource countries. It presents primarily as "acute viral hepatitis" syndrome, usually a self-limiting illness. A few cases progress to acute liver failure, a serious illness with high fatality. Clinical disease is infrequent among children. Infection during pregnancy is associated with a higher risk of symptomatic disease, severe liver injury, and mortality. Severe disease is also encountered in persons with preexisting chronic liver disease. Some cases have associated extrahepatic features, particularly acute pancreatitis and neurological manifestations. Chronic infection appears to be extremely infrequent with these HEV genotypes. The exact pathogenesis of liver injury remains unknown, although the host immune response appears to be important for viral clearance as well as for induction of liver injury. Hormonal and immune factors appear to be responsible for the severe disease during pregnancy.
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Affiliation(s)
- Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Amit Goel
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
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Lhomme S, Legrand-Abravanel F, Kamar N, Izopet J. Screening, diagnosis and risks associated with Hepatitis E virus infection. Expert Rev Anti Infect Ther 2019; 17:403-418. [DOI: 10.1080/14787210.2019.1613889] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Sébastien Lhomme
- Department of Virology, National reference center for Hepatitis E Virus, CHU Purpan, Toulouse, France
- Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
- Université de Toulouse, Toulouse III, Toulouse, France
| | - Florence Legrand-Abravanel
- Department of Virology, National reference center for Hepatitis E Virus, CHU Purpan, Toulouse, France
- Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
- Université de Toulouse, Toulouse III, Toulouse, France
| | - Nassim Kamar
- Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
- Université de Toulouse, Toulouse III, Toulouse, France
- Department of Nephrology and Organs Transplantation, CHU Rangueil, Toulouse, France
| | - Jacques Izopet
- Department of Virology, National reference center for Hepatitis E Virus, CHU Purpan, Toulouse, France
- Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
- Université de Toulouse, Toulouse III, Toulouse, France
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Choudhary MC, Bajpai V, Anand L, Gupta E. Guillain-Barré syndrome in a patient of acute Hepatitis E virus infection associated with genotype 1: Case report and literature review. Intractable Rare Dis Res 2019; 8:43-47. [PMID: 30881857 PMCID: PMC6409121 DOI: 10.5582/irdr.2018.01099] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Hepatitis E is a serious public health problem in developing countries. Most of the patients with Hepatitis E virus (HEV) infection present with typical acute hepatitis symptoms. However, in few patients it may lead to complications such as liver failure and extrahepatic symptoms. One of the rare extrahepatic presentations of this infection is neurological complications such as Guillain-Barré syndrome (GBS) which is observed in 5.5% of HEV infected patients (mainly in developed countries). Moreover, only genotype (gt) 3 HEV was found in association with GBS among patients in developed countries whereas molecular characterisation of HEV cases detected from developing countries have not been reported till now. Here, we are reporting a case of GBS as an extrahepatic complication of HEV associated with gt1 identified by molecular characterization by performing PCR of open-reading frame 2 (ORF2) region of HEV. Phylogenetic analysis by maximum likelihood method revealed that HEV gt1 case reported in this paper rooted closely with other HEV gt1 samples from South-Asian countries with high bootstrap values indicative of fully resolved tree.
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Affiliation(s)
- Manish Chandra Choudhary
- Department of Virology, Institute of Liver and Biliary Sciences, New Delhi, India
- Molecular and Cellular Medicine department, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vijeta Bajpai
- Department of Virology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Lovkesh Anand
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ekta Gupta
- Department of Virology, Institute of Liver and Biliary Sciences, New Delhi, India
- Address correspondence to:Dr. Ekta Gupta, Department of Virology, Institute of Liver and Biliary Sciences, New Delhi 110070, India. E-mail:
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Webb GW, Dalton HR. Hepatitis E: an underestimated emerging threat. Ther Adv Infect Dis 2019; 6:2049936119837162. [PMID: 30984394 PMCID: PMC6448100 DOI: 10.1177/2049936119837162] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 02/08/2019] [Indexed: 12/22/2022] Open
Abstract
Hepatitis E virus (HEV) is the most common cause of viral hepatitis in the world. It is estimated that millions of people are infected every year, resulting in tens of thousands of deaths. However, these estimates do not include industrialized regions and are based on studies which employ assays now known to have inferior sensitivity. As such, this is likely to represent a massive underestimate of the true global burden of disease. In the developing world, HEV causes large outbreaks and presents a significant public-health problem. Until recently HEV was thought to be uncommon in industrialized countries, and of little relevance to clinicians in these settings. We now know that this is incorrect, and that HEV is actually very common in developed regions. HEV has proved difficult to study in vitro, with reliable models only recently becoming available. Our understanding of the lifecycle of HEV is therefore incomplete. Routes of transmission vary by genotype and location: endemic regions experience large waterborne epidemics, while sporadic cases in industrialized regions are zoonotic infections likely spread via the food chain. Both acute and chronic infection has been observed, and a wide range of extrahepatic manifestations have been reported. This includes neurological, haematological and renal conditions. As the complete clinical phenotype of HEV infection is yet to be characterized, a large proportion of cases go unrecognized or misdiagnosed. In many cases HEV infection does not feature in the differential diagnosis due to a lack of knowledge and awareness of the disease amongst clinicians. In combination, these factors have contributed to an underestimation of the threat posed by HEV. Improvements are required in terms of recognition and diagnosis of HEV infection if we are to understand the natural history of the disease, improve management and reduce the burden of disease around the world.
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Affiliation(s)
- Glynn W. Webb
- University of Manchester NHS Foundation Trust, 7 Radnor Rd London NW6 6TT Manchester, UK
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Belbézier A, Lagrange E, Bouillet L. Trouble neurologique et hépatite E : revue de la littérature. Rev Med Interne 2018; 39:842-848. [DOI: 10.1016/j.revmed.2018.06.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Revised: 06/19/2018] [Accepted: 06/19/2018] [Indexed: 12/13/2022]
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