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Kanda T, Li TC, Takahashi M, Nagashima S, Primadharsini PP, Kunita S, Sasaki-Tanaka R, Inoue J, Tsuchiya A, Nakamoto S, Abe R, Fujiwara K, Yokosuka O, Suzuki R, Ishii K, Yotsuyanagi H, Okamoto H. Recent advances in hepatitis E virus research and the Japanese clinical practice guidelines for hepatitis E virus infection. Hepatol Res 2024; 54:1-30. [PMID: 38874115 DOI: 10.1111/hepr.14062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 04/22/2024] [Accepted: 05/09/2024] [Indexed: 06/15/2024]
Abstract
Acute hepatitis E was considered rare until reports emerged affirming the existence of hepatitis E virus (HEV) genotypes 3 and 4 infections in Japan in the early 2000s. Extensive studies by Japanese researchers have highlighted the pivotal role of pigs and wild animals, such as wild boars and deer, as reservoirs for HEV, linking them to zoonotic infections in Japan. Currently, when hepatitis occurs subsequent to the consumption of undercooked or grilled pork, wild boar meat, or offal (including pig liver and intestines), HEV infection should be considered. Following the approval of anti-HEV immunoglobulin A antibody as a diagnostic tool for hepatitis E by Japan's Health Insurance System in 2011, the annual number of diagnosed cases of HEV infection has surged. Notably, the occurrence of post-transfusion hepatitis E promoted nationwide screening of blood products for HEV using nucleic acid amplification tests since 2020. Furthermore, chronic hepatitis E has been observed in immunosuppressed individuals. Considering the significance of hepatitis E, heightened preventive measures are essential. The Japan Agency for Medical Research and Development Hepatitis A and E viruses (HAV and HEV) Study Group, which includes special virologists and hepatologists, held a virtual meeting on February 17, 2024. Discussions encompassed pathogenesis, transmission routes, diagnosis, complications, severity factors, and ongoing and prospective vaccination or treatments for hepatitis E. Rigorous assessment of referenced studies culminated in the formulation of recommendations, which are detailed within this review. This comprehensive review presents recent advancements in HEV research and Japanese clinical practice guidelines for HEV infection.
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Affiliation(s)
- Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
- Division of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minamiuonuma, Japan
- Division of Gastroenterology and Hepatology, Graduate School of Medicine and Dental Sciences, Niigata University, Niigata, Japan
| | - Tian-Cheng Li
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Putu Prathiwi Primadharsini
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Satoshi Kunita
- Center for Experimental Medicine, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
| | - Reina Sasaki-Tanaka
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
- Division of Gastroenterology and Hepatology, Graduate School of Medicine and Dental Sciences, Niigata University, Niigata, Japan
| | - Jun Inoue
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medicine and Dental Sciences, Niigata University, Niigata, Japan
| | - Shingo Nakamoto
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
| | - Ryuzo Abe
- Department of Emergency Medicine, Oita University, Oita, Japan
| | - Keiichi Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
| | - Ryosuke Suzuki
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Koji Ishii
- Department of Quality Assurance and Radiological Protection, National Institute of Infectious Diseases, Tokyo, Japan
| | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
- Department of Infectious Diseases and Applied Immunology, Hospital of the Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
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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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Pennella D, Giagio S, Maselli F, Giovannico G, Roncone A, Fiorentino F, Brindisino F. Red flags useful to screen for gastrointestinal and hepatic diseases in patients with shoulder pain: A scoping review. Musculoskeletal Care 2022; 20:721-730. [PMID: 35229444 DOI: 10.1002/msc.1628] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 02/13/2022] [Accepted: 02/14/2022] [Indexed: 01/01/2023]
Abstract
INTRODUCTION In most patients, shoulder pain has a neuromusculoskeletal cause. However, it might conceal other types of disorders, hiding a non-neuromusculoskeletal condition. The main aim of this scoping review is to map and summarise findings to identify red flags for gastrointestinal and hepatic diseases in the assessment of patients with shoulder pain. METHODS Five databases were searched up to 31 May 2021. Additional studies have been identified through grey literature, and the reference lists of the included studies have been screened. Any study design and publication type have been considered to be eligible for inclusion. No time, geographical setting and language restrictions have been applied. RESULTS A total of 157 records have been identified, with 40 studies meeting the inclusion criteria (37 case reports, 2 retrospective studies and 1 systematic review with meta-analysis). The most prevalent red flags associated with shoulder pain were abdominal pain (14 cases) and abdominal discomfort (3 cases), reported by 47% of patients. As for comorbidities, hepato-gastric, cardiac, visceral and systemic diseases were the most common ones. CONCLUSION Abdominal pain, right and left hypochondriac pain, and epigastric pain represent the most prevalent symptoms in patients with an abdominal disease that could mimic a shoulder problem. Clinicians should be encouraged to screen for red flags when assessing patients with shoulder pain.
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Affiliation(s)
- Denis Pennella
- Department of Medicine and Health Science "Vincenzo Tiberio", University of Molise, Campobasso, Italy
| | - Silvia Giagio
- Division of Occupational Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Filippo Maselli
- Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal Infantile, Sciences (DINOGMI), Campus of Savona, University of Genova, Savona, Italy
| | - Giuseppe Giovannico
- Department of Medicine and Health Science "Vincenzo Tiberio", University of Molise, Campobasso, Italy
| | - Antonella Roncone
- Department of Medicine and Health Science "Vincenzo Tiberio", University of Molise, Campobasso, Italy
| | - Fabio Fiorentino
- Department of Medicine and Health Science "Vincenzo Tiberio", University of Molise, Campobasso, Italy
| | - Fabrizio Brindisino
- Department of Medicine and Health Science "Vincenzo Tiberio", University of Molise, Campobasso, Italy
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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: 18] [Impact Index Per Article: 4.5] [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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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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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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Xin S, Xiao L. Clinical Manifestations of Hepatitis E. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 948:175-189. [PMID: 27738985 DOI: 10.1007/978-94-024-0942-0_10] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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 only 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)
- Shaojie Xin
- Liver Failure Treatment and Research Center, 302 Hospital, No.100 West 4th middle Road, Fengtai District, Beijing, 100039, China.
| | - Long Xiao
- Liver Failure Treatment and Research Center, 302 Hospital, No.100 West 4th middle Road, Fengtai District, Beijing, 100039, China
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8
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Pischke S, Hartl J, Pas SD, Lohse AW, Jacobs BC, Van der Eijk AA. Hepatitis E virus: Infection beyond the liver? J Hepatol 2017; 66:1082-1095. [PMID: 27913223 DOI: 10.1016/j.jhep.2016.11.016] [Citation(s) in RCA: 175] [Impact Index Per Article: 21.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Revised: 11/13/2016] [Accepted: 11/20/2016] [Indexed: 02/07/2023]
Abstract
Hepatitis E virus (HEV) infections are not limited to the liver but may also affect other organs. Several diseases, including Guillain-Barré syndrome, neuralgic amyotrophy, glomerulonephritis, cryoglobulinemia, pancreatitis, lymphoma, thrombopenia, meningitis, thyroiditis and myocarditis have been observed in the context of hepatitis E. To date, the definite pathophysiological links between HEV and extrahepatic manifestations are not yet established. However, it is suggested that HEV infection might be causative based on serological studies, case series, in vitro data and animal models. In particular, neuronal and renal diseases as well as pancreatitis seem to be caused by HEV, while a causative relationship between HEV and other diseases is more doubtful. Either direct cytopathic tissue damage by extrahepatic replication, or immunological processes induced by an overwhelming host immune response, are possible origins of HEV-associated extrahepatic manifestations. Hepatologists should be aware of the possibility that acute or chronically HEV-infected patients could develop extrahepatic manifestations. Neurologists, nephrologists, rheumatologists and other groups of physicians should consider HEV infection as a potential differential diagnosis when observing one of the diseases described in this review. Ribavirin and steroids have been used in small groups of patients with extrahepatic manifestations of HEV, but the efficacy of these drugs still needs to be verified by large, multicenter studies. This article comprehensively reviews the published literature regarding HEV and extrahepatic manifestations. We discuss the probability of specific extrahepatic diseases being caused by previous or ongoing HEV infection, and summarize the published knowledge about antiviral treatment in extrahepatic disorders.
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Affiliation(s)
- Sven Pischke
- Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
| | - Johannes Hartl
- Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Suzan D Pas
- Department of Viroscience, Erasmus MC University Medical Center Rotterdam, Netherlands
| | - Ansgar W Lohse
- Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Bart C Jacobs
- Department of Neurology and Immunology, Erasmus MC University Medical Center Rotterdam, Netherlands
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Velay A, Kack-Kack W, Abravanel F, Lhomme S, Leyendecker P, Kremer L, Chamouard P, Izopet J, Fafi-Kremer S, Barth H. Parsonage-Turner syndrome due to autochthonous acute genotype 3f hepatitis E virus infection in a nonimmunocompromised 55-year-old patient. J Neurovirol 2017; 23:615-620. [PMID: 28439773 DOI: 10.1007/s13365-017-0525-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Revised: 03/06/2017] [Accepted: 03/13/2017] [Indexed: 01/05/2023]
Abstract
Hepatitis E virus (HEV) infection is an emerging autochthonous disease in industrialized countries. Extra-hepatic manifestations, in particular neurologic manifestations, have been reported in HEV infection. Only a few cases of hepatitis E-associated Parsonage-Turner syndrome have been reported, and HEV genotypes were rarely determined. Here, we report the case of a Parsonage-Turner syndrome associated with an acute autochthonous HEV infection in a 55-year-old immunocompetent patient. HEV genomic RNA was detected in serum and cerebrospinal fluid samples (CSF), and molecular phylogenetic analysis of HEV was performed. The interest of this case lies in its detailed description notably the molecular analysis of HEV RNA isolated from serum and CSF. HEV infection should be considered in diagnostic investigations of neurologic manifestations associated with liver function perturbations.
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Affiliation(s)
- A Velay
- Virology Laboratory, University Hospital of Strasbourg, F-67000, Strasbourg, France. .,INSERM, IRM UMR-S 1109, F-67000, Strasbourg, France.
| | - W Kack-Kack
- Virology Laboratory, University Hospital of Strasbourg, F-67000, Strasbourg, France.,INSERM, IRM UMR-S 1109, F-67000, Strasbourg, France
| | - F Abravanel
- INSERM, U1043, Centre de Physiopathologie de Toulouse Purpan, F-31300, Toulouse, France.,CHU Toulouse Hôpital Purpan, Laboratoire de virologie, Institut fédératif de biologie de Purpan, F-31300, Toulouse, France
| | - S Lhomme
- INSERM, U1043, Centre de Physiopathologie de Toulouse Purpan, F-31300, Toulouse, France.,CHU Toulouse Hôpital Purpan, Laboratoire de virologie, Institut fédératif de biologie de Purpan, F-31300, Toulouse, France
| | - P Leyendecker
- Department of Neuroradiology, University Hospital of Strasbourg, F-67098, Strasbourg, France
| | - L Kremer
- Service de Neurologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.,Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, UMR_S INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France
| | - P Chamouard
- Department of Gastroenterology and Hepatology, University Hospital of Strasbourg, F-67098, Strasbourg, France
| | - J Izopet
- INSERM, U1043, Centre de Physiopathologie de Toulouse Purpan, F-31300, Toulouse, France.,CHU Toulouse Hôpital Purpan, Laboratoire de virologie, Institut fédératif de biologie de Purpan, F-31300, Toulouse, France
| | - S Fafi-Kremer
- Virology Laboratory, University Hospital of Strasbourg, F-67000, Strasbourg, France.,INSERM, IRM UMR-S 1109, F-67000, Strasbourg, France
| | - H Barth
- Virology Laboratory, University Hospital of Strasbourg, F-67000, Strasbourg, France.,INSERM, IRM UMR-S 1109, F-67000, Strasbourg, France
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Neuralgic Amyotrophy Associated With Hepatitis E Virus Infection: First Case in the United States. J Clin Neuromuscul Dis 2017; 18:96-100. [PMID: 27861224 DOI: 10.1097/cnd.0000000000000137] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Hepatitis E is an emerging viral infection in developed countries. It can present with multiple extra-hepatic manifestations, including neuralgic amyotrophy. We report a 52-year-old man who presented with neck and shoulder pain followed by orthopnea and left arm weakness. Electrodiagnostic testing showed left phrenic neuropathy and denervation in bilateral C5 and C6 myotomes. He also had elevated liver enzymes, which led to the diagnosis of acute hepatitis E. This is the first case of neuralgic amyotrophy associated with hepatitis E in the United States. Hepatitis E should be considered in patients with neuralgic amyotrophy, particularly men with bilateral symptoms, and if there is unexplained elevation of transaminases. The role of antiviral therapy remains unclear.
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11
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Intharasongkroh D, Sa-Nguanmoo P, Tuanthap S, Thongmee T, Duang-In A, Klinfueng S, Chansaenroj J, Vongpunsawad S, Theamboonlers A, Payungporn S, Chirathaworn C, Poovorawan Y. Hepatitis E Virus in Pork and Variety Meats Sold in Fresh Markets. FOOD AND ENVIRONMENTAL VIROLOGY 2017; 9:45-53. [PMID: 27580911 DOI: 10.1007/s12560-016-9258-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Accepted: 08/25/2016] [Indexed: 05/25/2023]
Abstract
Swine is an economically important livestock, yet pork consumption and close contact with pigs are associated with the risk of hepatitis E virus (HEV) infection. Limited data on the prevalence of HEV in Southeast Asia have mainly examined farm animals. To investigate the potential zoonotic transmission of HEV from dietary consumption of pork and variety meats (i.e., offal or organ meats), we obtained 1090 liver, 559 pork meat, and 556 intestine samples from fresh markets in the Bangkok metropolitan area between November 2014 and February 2015. The presence of HEV was assessed using reverse-transcription polymerase chain reaction. Concurrently, 720 bile and 553 fecal samples from a slaughterhouse were also examined. Overall, HEV RNA was found in 0.23 % of the market samples and 3.93 % of the slaughterhouse samples. Fecal and bile samples were more likely to test positive compared to liver, pork, and intestine samples (p < 0.001). Phylogenetic analysis showed that all HEV sequences obtained in this study formed a cluster closely related to genotype 3f. Pork and variety meats derived from pigs are commonly sold in fresh markets throughout Southeast Asia. Here, a relatively low HEV prevalence from pork and variety meats sold in Bangkok was found. Additional studies will be required to further assess potential dietary transmission of HEV elsewhere in the region.
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Affiliation(s)
- Duangnapa Intharasongkroh
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Pattaratida Sa-Nguanmoo
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Supansa Tuanthap
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Thanunrat Thongmee
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Ausanee Duang-In
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sirapa Klinfueng
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Jira Chansaenroj
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sompong Vongpunsawad
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Apiradee Theamboonlers
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sunchai Payungporn
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Chintana Chirathaworn
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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Neuralgic amyotrophy triggered by hepatitis E virus: a particular phenotype. J Neurol 2017; 264:770-780. [PMID: 28247042 DOI: 10.1007/s00415-017-8433-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Revised: 02/19/2017] [Accepted: 02/20/2017] [Indexed: 01/12/2023]
Abstract
The neuralgic amyotrophy may be of difficult diagnosis, due to phenotypic variability, with different initial presentations (upper plexus multiple mononeuropathy, lumbosacral involvement, distal reached, phrenic involvement). To date, there is little guidance on these patients' therapeutic management, especially those for which neuralgic amyotrophy is triggered by hepatitis E virus (HEV-NA). The study aims to identify specific features that characterize patients bearing the neuralgic amyotrophy triggered by HEV. We first describe a new case report of HEV-neuralgic amyotrophy, with delayed diaphragmatic reach. Then, the literature was searched for reports of HEV-NA (n = 39), and neuralgic amyotrophy with phrenic paresis (n = 42) from 1999 to June 2016. Relevant data were retrieved, analyzed and compared with the parameters of idiopathic neuralgic amyotrophy (n = 199) of the largest cohort, described by Van Alfen and Van Engelen in 2006. Compared to the published cohort, HEV-NA patients were more likely to be men (M/F 34/5 vs. 136/63, p = 0.017), with more frequent bilateral symptoms (86.8% cases vs. 28.5%, p < 0.0001) as well as phrenic paresis (18.0 vs. 6.6%, p = 0.028). The clinical improvement is poor, with 15.6% of cases with remission only. A particular phenotype characteristic of the HEV-induced neuralgic amyotrophy has arisen. Our findings call for action in validating the above-mentioned features that illustrate the HEV-NA cases as an early diagnosis would prevent complications, especially the phrenic damage often associated with a worse functional outcome.
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13
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Shi R, Soomro MH, She R, Yang Y, Wang T, Wu Q, Li H, Hao W. Evidence of Hepatitis E virus breaking through the blood-brain barrier and replicating in the central nervous system. J Viral Hepat 2016; 23:930-939. [PMID: 27329366 DOI: 10.1111/jvh.12557] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Accepted: 05/03/2016] [Indexed: 12/12/2022]
Abstract
Neurologic dysfunctions such as Guillain-Barre' syndrome, encephalitis, meningitis and transverse myelitis occur frequently in patients with hepatitis E virus (HEV) infection, and this study was conducted to better characterize the role of HEV in the pathogenesis of neurologic disorders. Genotype 4 strain of swine HEV was used to inoculate Mongolian gerbils. Reverse transcription-nested polymerase chain reaction (RT-nPCR), ELISA, histopathology, ultrastructural pathology and enzyme immunohistochemistry method were conducted to investigate the replication and localization of HEV in the central nervous system (CNS) and the consequent pathological changes. Both positive- and negative-strand HEV RNA was detectable in brain and spinal cord from 7 to 28 dpi (days postinoculation) via RT-nPCR. Various pathological changes such as perineural invasion, neuron necrosis, microglia nodule, lymphocyte infiltration, perivascular cuff and myelin degeneration were observed in HEV-positive brains and spinal cords. Immunohistochemical (IHC) staining targeting on HEV ORF2 protein revealed positive signals concentrated mainly in the cytoplasm of neuron, ependymal epithelium and choroid plexus area. Positive area density of ZO-1 (zonula occludens-1) in brain of HEV-positive gerbils decreased, while the GFAP (glial fibrillary acidic protein) expression was upregulated compared with control groups. These results provide strong evidence that HEV is able to damage the blood-brain barrier (BBB), replicate in brain and spinal cord, and hammer the causative role of HEV in the pathogenesis of neurologic disorders.
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Affiliation(s)
- R Shi
- Laboratory of Animal Pathology and Public Health, Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agriculture University, Beijing, China
| | - M H Soomro
- Laboratory of Animal Pathology and Public Health, Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agriculture University, Beijing, China
| | - R She
- Laboratory of Animal Pathology and Public Health, Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agriculture University, Beijing, China.
| | - Y Yang
- Laboratory of Animal Pathology and Public Health, Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agriculture University, Beijing, China
| | - T Wang
- Laboratory of Animal Pathology and Public Health, Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agriculture University, Beijing, China
| | - Q Wu
- Laboratory of Animal Pathology and Public Health, Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agriculture University, Beijing, China
| | - H Li
- Laboratory of Animal Pathology and Public Health, Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agriculture University, Beijing, China
| | - W Hao
- Laboratory of Animal Pathology and Public Health, Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agriculture University, Beijing, China
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14
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Dalton HR, Kamar N, van Eijk JJJ, Mclean BN, Cintas P, Bendall RP, Jacobs BC. Hepatitis E virus and neurological injury. Nat Rev Neurol 2015; 12:77-85. [PMID: 26711839 DOI: 10.1038/nrneurol.2015.234] [Citation(s) in RCA: 166] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Hepatitis E is hyperendemic in many developing countries in Asia and Africa, and is caused by hepatitis E virus (HEV) genotypes 1 and 2, which are spread via the faecal-oral route by contaminated water. Recent data show that HEV infection is also endemic in developed countries. In such geographical settings, hepatitis E is caused by HEV genotypes 3 and 4, and is mainly a porcine zoonosis. In a minority of cases, HEV causes acute and chronic hepatitis, but infection is commonly asymptomatic or unrecognized. HEV infection is associated with a number of extrahepatic manifestations, including a range of neurological injuries. To date, 91 cases of HEV-associated neurological injury--most commonly, Guillain-Barré syndrome, neuralgic amyotrophy, and encephalitis/myelitis--have been reported. Here, we review the reported cases, discuss possible pathogenic mechanisms, and present our perspectives on future directions and research questions.
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Affiliation(s)
- Harry R Dalton
- Royal Cornwall Hospital, University of Exeter, Penventinnie Lane, Truro TR1 3LJ, UK.,European Centre for Environment &Human Health, University of Exeter, Penventinnie Lane, Truro TR1 3LJ, UK
| | - Nassim Kamar
- Departments of Nephrology and Organ Transplantation, CHU Rangueil, INSERM U1043, IFR-BMT, Université Paul Sabatier, 1 Avenue J. Poulhès, Toulouse Cedex 9, France
| | - Jeroen J J van Eijk
- Department of Neurology, Jeroen Bosch Ziekenhuis (JBZ), Henri Dunantstraat 1, 5223 GZ, 's-Hertogenbosch, Netherlands
| | - Brendan N Mclean
- Royal Cornwall Hospital, University of Exeter, Penventinnie Lane, Truro TR1 3LJ, UK
| | - Pascal Cintas
- Department of Neurology, Pierre Paul Riquet Hospital, CHU Purpan, Place du Dr Baylac, 31059 Toulouse, France
| | - Richard P Bendall
- Royal Cornwall Hospital, University of Exeter, Penventinnie Lane, Truro TR1 3LJ, UK.,European Centre for Environment &Human Health, University of Exeter, Penventinnie Lane, Truro TR1 3LJ, UK
| | - Bart C Jacobs
- Department of Neurology/Neuro-Immunology Erasmus MC, Erasmus MC, Afdeling Neurologie, Kamer EE 2287, Postbus 2040, 3000 CA Rotterdam, Netherlands
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15
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Lee GY, Poovorawan K, Intharasongkroh D, Sa-nguanmoo P, Vongpunsawad S, Chirathaworn C, Poovorawan Y. Hepatitis E virus infection: Epidemiology and treatment implications. World J Virol 2015; 4:343-355. [PMID: 26568916 PMCID: PMC4641226 DOI: 10.5501/wjv.v4.i4.343] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2015] [Revised: 08/06/2015] [Accepted: 09/16/2015] [Indexed: 02/05/2023] Open
Abstract
Hepatitis E virus (HEV) infection is now established as an emerging enteric viral hepatitis. Standard treatments in acute and chronic hepatitis E remain to be established. This study undertakes a review of the epidemiology, treatment implication and vaccine prevention from published literature. HEV infection is a worldwide public health problem and can cause acute and chronic hepatitis E. HEV genotypes 1 and 2 are primarily found in developing countries due to waterborne transmission, while the zoonotic potential of genotypes 3 and 4 affects mostly industrialized countries. An awareness of HEV transmission through blood donation, especially in the immunocompromised and solid organ transplant patients, merits an effective anti-viral therapy. There are currently no clear indications for the treatment of acute hepatitis E. Despite concerns for side effects, ribavirin monotherapy or in combination with pegylated interferon alpha for at least 3 mo appeared to show significant efficacy in the treatment of chronic hepatitis E. However, there are no available treatment options for specific patient population groups, such as women who are pregnant. Vaccination and screening of HEV in blood donors are currently a global priority in managing infection. New strategies for the treatment and control of hepatitis E are required for both acute and chronic infections, such as prophylactic use of medications, controlling large outbreaks, and finding acceptable antiviral therapy for pregnant women and other patient groups for whom the current options of treatment are not viable.
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16
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Bazerbachi F, Haffar S, Garg SK, Lake JR. Extra-hepatic manifestations associated with hepatitis E virus infection: a comprehensive review of the literature. Gastroenterol Rep (Oxf) 2015; 4:1-15. [PMID: 26358655 PMCID: PMC4760069 DOI: 10.1093/gastro/gov042] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2015] [Accepted: 07/09/2015] [Indexed: 02/07/2023] Open
Abstract
Background and aims: Hepatitis E virus (HEV) infection is a significant public health problem that afflicts almost 20 million individuals annually and causes acute liver injury in 3.5 million, with approximately 56 000 deaths. As with other viral hepatitides, extra-hepatic manifestations could represent an important aspect of this infection. The spectrum of these manifestations is still emerging. Acute pancreatitis and neurological, musculoskeletal, hematological, renal, and other immune-mediated manifestations have been described. The aim of this article is to comprehensively review the published literature of extra-hepatic manifestations associated with HEV infection. Data sources: We searched the PubMed database using the MeSH term “hepatitis E” and each of the extra-hepatic manifestations associated with HEV infection. No language or date restrictions were set in these searches. Searches retrieving articles with non-A, non-B hepatitis were excluded. Additional articles were identified through the reference lists of included articles. Results: Several extra-hepatic manifestations associated with HEV infection have been published. The temporal association between some extra-hepatic manifestations and HEV infection and the exclusion of other possible etiologies suggests that HEV infection could have caused some of them. According to the available data, HEV infection appears to be strongly associated with acute pancreatitis, neurological disorders (with primarily dominant peripheral nerve involvement, most commonly manifested as Guillain-Barré syndrome, followed by neuralgic amyotrophy), hematological diseases (hemolytic anemia due to glucose phosphate dehydrogenase deficiency, and severe thrombocytopenia), glomerulonephritis, and mixed cryoglobulinemia. More data are needed to clarify whether an association exists with musculoskeletal or other immune-mediated manifestations. Conclusions: HEV infection should be considered in patients with acute pancreatitis, Guillain-Barré syndrome, neuralgic amyotrophy, hemolytic anemia due to glucose phosphate dehydrogenase deficiency, severe thrombocytopenia, glomerulonephritis, and mixed cryoglobulinemia. Alternatively, signs and symptoms of these conditions should be sought in patients with acute or chronic HEV infection. More data are needed to confirm the role of HEV in other extra-hepatic disorders.
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Affiliation(s)
- Fateh Bazerbachi
- Division of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Samir Haffar
- Department of Gastroenterology and Hepatology, University of Damascus, Damascus, Syrian Arab Republic
| | - Sushil K Garg
- Division of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, MN 55455, USA
| | - John R Lake
- Division of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, MN 55455, USA
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17
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Sarkar P, Morgan C, Ijaz S. Transverse myelitis caused by hepatitis E: previously undescribed in adults. BMJ Case Rep 2015; 2015:bcr-2014-209031. [PMID: 26150621 DOI: 10.1136/bcr-2014-209031] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
We report the case of a 62-year-old Caucasian woman who was admitted with urinary retention and lower limb paraesthesia following a week's prodromal illness of headache and malaise. Liver function tests showed a picture of acute hepatocellular dysfunction. She developed reduced lower limb power, brisk reflexes, extensor plantars, a sensory level at T8 and reduced anal sphincter tone, establishing a clinical diagnosis of transverse myelitis. A spinal MRI showed no evidence of cauda equina or spinal cord compression. Cerebrospinal fluid (CSF) analysis showed raised protein and raised white cell count. Hepatitis E IgM and IgG were positive and hepatitis E virus was found in her CSF. She was treated with methylprednisolone and is slowly recovering with physiotherapy.
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Affiliation(s)
- Pamela Sarkar
- Department of Neurology, Southmead Hospital, Bristol, UK
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18
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Dartevel A, Colombe B, Bosseray A, Larrat S, Sarrot-Reynauld F, Belbezier A, Lagrange E, Bouillet L. Hepatitis E and neuralgic amyotrophy: Five cases and review of literature. J Clin Virol 2015. [PMID: 26209399 DOI: 10.1016/j.jcv.2015.06.091] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Hepatitis E virus infection - mainly genotype 3 - is increasingly common in industrialized countries. Infection is usually asymptomatic, but cases of central or peripheral neurological symptoms with hepatitis E have been described. The most frequent is Guillain-Barre but somes cases of neuralgic amyotrophy have been described. In our center, since 2010, we have identified five cases of neuralgic amyotrophy associated with acute hepatitis E in immunocompetent patients. For all these patients, neuralgic amyotrophy was diagnosed with electromyogram and positive IgM for hepatitis E, and detectable HEV RNA in 4 of the cases. Including our patients, we count 26 cases in literature. The mean age of the patients was 44 years old, with a large predominance of males (88%). The disorder is bilateral and asymmetric in 69% of cases. Peripheral nerves other than the brachial plexus were affected in 6 patients (23%). In industrialized countries, any neuralgic amyotrophy, particularly if there is bilateral, asymmetric associated with involvement of nerves outside the brachial plexus, should lead physicians to consider a diagnosis of acute hepatitis E.
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Affiliation(s)
- Anaïs Dartevel
- Internal Medicine Department, Grenoble University Hospital, France.
| | - Barbara Colombe
- Internal Medicine Department, Grenoble University Hospital, France
| | - Annick Bosseray
- Internal Medicine Department, Grenoble University Hospital, France
| | - Sylvie Larrat
- Virology Department, Reference Center of Neuromuscular Disease, Grenoble University Hospital, France
| | | | - Aude Belbezier
- Internal Medicine Department, Grenoble University Hospital, France
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19
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Martínez Rodríguez L, Carvajal P, Morís G. [Neuralgic amyotrophy associated to hepatitis E virus infection]. Med Clin (Barc) 2015; 145:462-3. [PMID: 25817452 DOI: 10.1016/j.medcli.2015.01.021] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2014] [Revised: 01/24/2015] [Accepted: 01/29/2015] [Indexed: 12/20/2022]
Affiliation(s)
| | - Paula Carvajal
- Servicio de Neurofisiología Clínica, Hospital Universitario Central de Asturias, Oviedo, Asturias, España
| | - Germán Morís
- Servicio de Neurología, Hospital Universitario Central de Asturias, Oviedo, Asturias, España.
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20
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Décard BF, Grimm A, Andelova M, Deman A, Banderet B, Garcia M, Fuhr P. Hepatitis-E virus associated neuralgic amyotrophy with sustained plexus brachialis swelling visualized by high-resolution ultrasound. J Neurol Sci 2015; 351:208-210. [PMID: 25769655 DOI: 10.1016/j.jns.2015.03.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2014] [Revised: 02/13/2015] [Accepted: 03/01/2015] [Indexed: 01/12/2023]
Affiliation(s)
| | - Alexander Grimm
- Department of Neurology, University Hospital Basel, Switzerland
| | | | - Anna Deman
- Department of Internal Medicine, University Hospital Basel, Switzerland
| | - Bettina Banderet
- Department of Internal Medicine, University Hospital Basel, Switzerland
| | - Meritxell Garcia
- Department of Neuroradiology, Clinic for Radiology and Nuclear Medicine, University Hospital Basel, Switzerland
| | - Peter Fuhr
- Department of Neurology, University Hospital Basel, Switzerland
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21
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Abstract
Hepatitis E virus infection is an emerging disease in developed countries. Acute and chronic infection has been reported, with chronic infection being increasingly reported in immunocompromised patients. Neurological disorders are an emerging manifestation of both acute and chronic hepatitis E virus infection. We report a 77-year-old female presented with paraesthesia and was found to have abnormal liver function tests. Serology was found to be positive for hepatitis E virus IgM, IgG and RNA. Liver function tests normalised after three weeks and her neurological symptoms completely resolved. To our knowledge, this is the first case in Scotland of hepatitis E virus presenting only with neurological symptoms.
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Affiliation(s)
- Susan Bennett
- Pre-registered Clinical Scientist, West of Scotland Specialist Virology Centre, Glasgow Royal Infirmary, UK
| | - Kathy Li
- SPR in Virology, West of Scotland Specialist Virology Centre, Glasgow Royal Infirmary, UK
| | - Rory N Gunson
- Consultant Clinical Scientist, West of Scotland Specialist Virology Centre, Glasgow Royal Infirmary, UK
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22
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Poovorawan K, Jitmitrapab S, Treeprasertsuk S, Thongmee T, Theamboonlers A, Tangkijvanich P, Komolmit P, Poovorawan Y. Risk factors and molecular characterization of acute sporadic symptomatic hepatitis E virus infection in Thailand. ASIAN PAC J TROP MED 2014; 7:709-714. [DOI: 10.1016/s1995-7645(14)60121-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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23
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Abstract
Hepatitis E virus (HEV) infection is a worldwide disease. An improved understanding of the natural history of HEV infection has been achieved within the last decade. Several reservoirs and transmission modes have been identified. Hepatitis E is an underdiagnosed disease, in part due to the use of serological assays with low sensitivity. However, diagnostic tools, including nucleic acid-based tests, have been improved. The epidemiology and clinical features of hepatitis E differ between developing and developed countries. HEV infection is usually an acute self-limiting disease, but in developed countries it causes chronic infection with rapidly progressive cirrhosis in organ transplant recipients, patients with hematological malignancy requiring chemotherapy, and individuals with HIV. HEV also causes extrahepatic manifestations, including a number of neurological syndromes and renal injury. Acute infection usually requires no treatment, but chronic infection should be treated by reducing immunosuppression in transplant patients and/or the use of antiviral therapy. In this comprehensive review, we summarize the current knowledge about the virus itself, as well as the epidemiology, diagnostics, natural history, and management of HEV infection in developing and developed countries.
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24
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van Eijk JJJ, Madden RG, van der Eijk AA, Hunter JG, Reimerink JHJ, Bendall RP, Pas SD, Ellis V, van Alfen N, Beynon L, Southwell L, McLean B, Jacobs BC, van Engelen BGM, Dalton HR. Neuralgic amyotrophy and hepatitis E virus infection. Neurology 2014; 82:498-503. [PMID: 24401685 PMCID: PMC3937863 DOI: 10.1212/wnl.0000000000000112] [Citation(s) in RCA: 136] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2013] [Accepted: 11/22/2013] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVE To determine whether there is an association between an acute preceding hepatitis E virus (HEV) infection and neuralgic amyotrophy (NA), and if so, whether patients with HEV-related NA differ from patients without an associated HEV infection. METHODS HEV testing was conducted in a retrospective cohort of 28 Cornish patients with NA (2011-2013) and a prospective cohort of 38 consecutive Dutch patients with NA (2004-2007). Acute-phase serum samples were analyzed for the presence of anti-HEV immunoglobulin (Ig) M and IgG and HEV RNA (quantitative real-time PCR). RESULTS Five cases (10.6%) of acute hepatitis E infection were identified in a total group of 47 patients with NA of whom serum samples were available. In 4 patients, HEV RNA was detected in serum samples taken at presentation. All patients with HEV-associated NA had clinical and electrophysiologic evidence of bilateral brachial plexus involvement. Anti-HEV IgM positivity was not related to age, sex, disease severity, disease course, or outcome. CONCLUSIONS Acute hepatitis E is found in 10% of patients with NA from the United Kingdom and the Netherlands. Further research is required to investigate the role of HEV in NA in other geographical locations and to determine pathophysiologic mechanisms.
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Affiliation(s)
- Jeroen J J van Eijk
- From the Department of Neurology (J.J.J.v.E., N.v.A., B.G.M.v.E.), Radboud University Nijmegen Medical Centre; Department of Neurology (J.J.J.v.E.), Jeroen Bosch Hospital, Nijmegen, the Netherlands; Cornwall Gastrointestinal Unit (R.G.M., J.G.H., L.B., L.S., H.R.D.), Clinical Microbiology (R.P.B., V.E.), and Department of Neurology (B.M.), Royal Cornwall Hospital Trust; European Centre for the Environment and Human Health (R.G.M., J.G.H., R.P.B., L.B., H.R.D.), University of Exeter Medical School, Truro, UK; Centre for Infectious Disease Control (J.H.J.R.), Division Virology, National Institute for Public Health and the Environment, Bilthoven; Departments of Viroscience (A.A.v.d.E., S.D.P.), Immunology (B.C.J.), and Neurology (B.C.J.), Erasmus Medical Centre, University Medical Center Rotterdam, the Netherlands
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25
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Motte A, Franques J, Weitten T, Colson P. Hepatitis E-associated Parsonage-Turner syndrome, France. Clin Res Hepatol Gastroenterol 2014; 38:e11-4. [PMID: 24246798 DOI: 10.1016/j.clinre.2013.08.011] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2013] [Accepted: 08/27/2013] [Indexed: 02/04/2023]
Affiliation(s)
- Anne Motte
- Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Centre Hospitalo-Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, 264, rue Saint-Pierre, 13385 Marseille cedex 05, France
| | - Jérôme Franques
- Centre de Référence des Maladies Neuromusculaires et de la SLA, Centre Hospitalo-Universitaire Timone, 264, rue Saint-Pierre, 13385 Marseille cedex 05, France
| | - Thierry Weitten
- Service de Médecine interne, Centre Hospitalier Intercommunal des Alpes du Sud, 1, place Auguste-Muret, BP 101, 05007 Gap cedex, France
| | - Philippe Colson
- Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Centre Hospitalo-Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, 264, rue Saint-Pierre, 13385 Marseille cedex 05, France; Aix-Marseille Université, URMITE UM 63 CNRS 7278 IRD 198 INSERM U1905, Facultés de Médecine et de Pharmacie, 27, boulevard Jean-Moulin, 13385 Marseille cedex 05, France.
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26
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Parvez MK. Hepatitis E Virus-Associated Neuropathy: An Emerging Extrahepatic Manifestation. Future Virol 2014; 9:1-4. [DOI: 10.2217/fvl.13.120] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Affiliation(s)
- Mohammad Khalid Parvez
- Department of Pharmacognosy, King Saud University College of Pharmacy, Riyadh11451, Saudi Arabia
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27
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Sellner J, Steiner I. Neurologic complications of hepatic viruses. HANDBOOK OF CLINICAL NEUROLOGY 2014; 123:647-61. [PMID: 25015509 DOI: 10.1016/b978-0-444-53488-0.00031-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Johann Sellner
- Department of Neurology, Christian-Doppler-Klinik, Paracelsus Medical University, Salzburg, Austria; Department of Neurology, Klinikum rechts der Isar, Technische Universität Munich, Germany
| | - Israel Steiner
- Department of Neurology, Rabin Medical Center, Petach Tikva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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28
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Kamar N, Izopet J, Dalton HR. Chronic hepatitis e virus infection and treatment. J Clin Exp Hepatol 2013; 3:134-40. [PMID: 25755487 PMCID: PMC3940092 DOI: 10.1016/j.jceh.2013.05.003] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2013] [Accepted: 05/07/2013] [Indexed: 12/12/2022] Open
Abstract
It is now well accepted that hepatitis E virus (HEV) infection can induce chronic hepatitis and cirrhosis in immunosuppressed patients. Chronic genotype-3 HEV infections were first reported in patients with a solid-organ transplant. Thereafter, cases of chronic HEV infection have been reported in patients with hematological disease and in those who are human immunodeficiency virus (HIV)-positive. HEV-associated extra-hepatic manifestations, including neurological symptoms, kidney injuries, and hematological disorders, have been also reported. In transplant patients, reducing the dosage of immunosuppressive drugs allows the virus to be cleared in some patients. In the remaining patients, as well as hematological patients and patients who are HIV-positive, anti-viral therapies, such as pegylated interferon and ribavirin, have been found to be efficient in eradicating HEV infection. This review summarizes our current knowledge of chronic HEV infection, its treatment, and the extra-hepatic manifestations induced by HEV.
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Affiliation(s)
- Nassim Kamar
- Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, Toulouse, France
- INSERM U1043, IFR–BMT, CHU Purpan, Toulouse, France
- Université Paul Sabatier, Toulouse, France
| | - Jacques Izopet
- INSERM U1043, IFR–BMT, CHU Purpan, Toulouse, France
- Université Paul Sabatier, Toulouse, France
- Department of Virology, CHU Purpan, Toulouse, France
| | - Harry R. Dalton
- Cornwall Gastrointestinal Unit, Royal Cornwall Hospital and European Centre of Environment and Human Health, University of Exeter Medical School, Truro, UK
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Inghilleri ML, Grini Mazouzi M, Juntas Morales R. [Neuralgic amyotrophy as a manifestation of hepatitis E infection]. Rev Neurol (Paris) 2012; 168:383-4. [PMID: 22398219 DOI: 10.1016/j.neurol.2011.07.014] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2011] [Revised: 07/10/2011] [Accepted: 07/22/2011] [Indexed: 01/12/2023]
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Jha AK, Nijhawan S, Nepalia S, Suchismita A. Association of Bell's Palsy with Hepatitis E Virus Infection: A Rare Entity. J Clin Exp Hepatol 2012; 2:88-90. [PMID: 25755411 PMCID: PMC3940373 DOI: 10.1016/s0973-6883(12)60082-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2011] [Accepted: 02/06/2012] [Indexed: 12/12/2022] Open
Abstract
Hepatitis E virus (HEV) infection is a common cause of acute hepatitis in India and other developing countries. The data regarding the neurologic manifestation of HEV infection are limited. The neurologic disorders including Guillain-Barré syndrome, polyradiculopathy, neuralgic amyotrophy, encephalitis, bilateral brachial neuritis, ataxia/proximal myopathy, and acute transverse myelitis have been described. Bell's palsy and other cranial nerve involvement in hepatitis A virus (HAV) and HEV infection are rare. We present the second case of Bell's palsy associated with HEV.
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Affiliation(s)
- Ashish K Jha
- Department of Gastroenterology, SMS Medical College, Jaipur, India
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Kamar N, Bendall RP, Peron JM, Cintas P, Prudhomme L, Mansuy JM, Rostaing L, Keane F, Ijaz S, Izopet J, Dalton HR. Hepatitis E virus and neurologic disorders. Emerg Infect Dis 2011; 17:173-9. [PMID: 21291585 PMCID: PMC3298379 DOI: 10.3201/eid1702.100856] [Citation(s) in RCA: 214] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Affiliation(s)
- Nassim Kamar
- Department of Nephrology, Dialysis and Organ Transplantation, Centre Hospitalier Universitaire Rangueil, Toulouse, France.
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Suwannakarn K, Tongmee C, Theamboonlers A, Komolmit P, Poovorawan Y. Swine as the possible source of hepatitis E virus transmission to humans in Thailand. Arch Virol 2010; 155:1697-1699. [PMID: 20628771 DOI: 10.1007/s00705-010-0751-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2010] [Accepted: 07/05/2010] [Indexed: 11/28/2022]
Abstract
This report describes a study that provides evidence of HEV transmission from pigs to humans in Thailand by applying molecular genetics analysis. It was found that viruses recovered from Thai patients are closely related to genotype 3 and swine hepatitis E virus in Thailand. Based on analysis of a 302-base-pair ORF2 fragment, the strains investigated belong to subgroup 3e and are closely related to European strains. Based on the results obtained, swine are suspected to be a source of HEV transmission to humans in Thailand.
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Affiliation(s)
- Kamol Suwannakarn
- Department of Pediatrics, Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University and Hospital, Bangkok, Thailand
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