|
1
|
Pavlova A, Kocikova B, Dolinska MU, Jackova A. Hepatitis E Virus in the Role of an Emerging Food-Borne Pathogen. Microorganisms 2025; 13:885. [PMID: 40284721 PMCID: PMC12029509 DOI: 10.3390/microorganisms13040885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Revised: 04/04/2025] [Accepted: 04/07/2025] [Indexed: 04/29/2025] Open
Abstract
Viral hepatitis E represents an important global health problem caused by the hepatitis E virus (HEV). Cases of HEV infection are increasingly associated with food-borne transmissions after the consumption of raw or undercooked food products from infected animals in high-income regions. Although most cases of infection are asymptomatic, severe courses of infection have been reported in specific groups of people, predominantly among pregnant women and immunocompromised patients. The viral nucleic acid of HEV is increasingly being reported in food-producing animals and different products of an animal origin. Even though the incubation period for HEV infection is long, several direct epidemiological links between human cases and the consumption of HEV-contaminated meat and meat products have been described. In this article, we review the current knowledge on human HEV infections, HEV in different food-producing animals and products of an animal origin, as well as the accumulation and resistance to HEV in farm and slaughterhouse environments. We also provide preventive measures to help eliminate HEV from animals, the human population, and the environment.
Collapse
Affiliation(s)
| | | | | | - Anna Jackova
- Department of Epizootiology, Parasitology and Protection of One Health, University of Veterinary Medicine and Pharmacy in Kosice, Komenskeho 73, 041 81 Kosice, Slovakia; (A.P.); (B.K.); (M.U.D.)
| |
Collapse
|
|
2
|
Chen K, Gao Z. Acacetin, a Natural Flavone with Potential in Improving Liver Disease Based on Its Anti-Inflammation, Anti-Cancer, Anti-Infection and Other Effects. Molecules 2024; 29:4872. [PMID: 39459239 PMCID: PMC11509893 DOI: 10.3390/molecules29204872] [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: 09/19/2024] [Revised: 10/07/2024] [Accepted: 10/12/2024] [Indexed: 10/28/2024] Open
Abstract
Liver disease is a global public problem, and the cost of its therapy is a large financial burden to governments. It is well known that drug therapy plays a critical role in the treatment of liver disease. However, present drugs are far from meeting clinical needs. Lots of efforts have been made to find novel agents to treat liver disease in the past several decades. Acacetin is a dihydroxy and monomethoxy flavone, named 5,7-dihydroxy-4'-methoxyflavone, which can be found in diverse plants. It has been reported that acacetin exhibits multiple pharmacological activities, including anti-cancer, anti-inflammation, anti-virus, anti-obesity, and anti-oxidation. These studies indicate the therapeutic potential of acacetin in liver disease. This review discussed the comprehensive information on the pathogenesis of liver disease (cirrhosis, viral hepatitis, drug-induced liver injury, and hepatocellular carcinoma), then introduced the biological source, structural features, and pharmacological properties of acacetin, and the possible application in preventing liver disease along with the pharmacokinetic and toxicity of acacetin, and future research directions. We systemically summarized the latest research progress on the potential therapeutic effect of acacetin on liver disease and existing problems. Based on the present published information, the natural flavone acacetin is an anticipated candidate agent for the treatment of liver disease.
Collapse
Affiliation(s)
- Kuihao Chen
- Department of Pharmacology, School of Medicine, Ningbo University, 818 Fenghua Rd., Ningbo 315211, China
| | - Zhe Gao
- Department of Pharmacy, Zhejiang Pharmaceutical University, 666 Siming Rd., Ningbo 315211, China
| |
Collapse
|
|
3
|
Orosz L, Sárvári KP, Dernovics Á, Rosztóczy A, Megyeri K. Pathogenesis and clinical features of severe hepatitis E virus infection. World J Virol 2024; 13:91580. [PMID: 38984076 PMCID: PMC11229844 DOI: 10.5501/wjv.v13.i2.91580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 02/08/2024] [Accepted: 04/15/2024] [Indexed: 06/24/2024] Open
Abstract
The hepatitis E virus (HEV), a member of the Hepeviridae family, is a small, non-enveloped icosahedral virus divided into eight distinct genotypes (HEV-1 to HEV-8). Only genotypes 1 to 4 are known to cause diseases in humans. Genotypes 1 and 2 commonly spread via fecal-oral transmission, often through the consumption of contaminated water. Genotypes 3 and 4 are known to infect pigs, deer, and wild boars, often transferring to humans through inadequately cooked meat. Acute hepatitis caused by HEV in healthy individuals is mostly asymptomatic or associated with minor symptoms, such as jaundice. However, in immunosuppressed individuals, the disease can progress to chronic hepatitis and even escalate to cirrhosis. For pregnant women, an HEV infection can cause fulminant liver failure, with a potential mortality rate of 25%. Mortality rates also rise amongst cirrhotic patients when they contract an acute HEV infection, which can even trigger acute-on-chronic liver failure if layered onto pre-existing chronic liver disease. As the prevalence of HEV infection continues to rise worldwide, highlighting the particular risks associated with severe HEV infection is of major medical interest. This text offers a brief summary of the characteristics of hepatitis developed by patient groups at an elevated risk of severe HEV infection.
Collapse
Affiliation(s)
- László Orosz
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
| | - Károly Péter Sárvári
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
| | - Áron Dernovics
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
| | - András Rosztóczy
- Department of Internal Medicine, Division of Gastroenterology, University of Szeged, Szeged 6725, Csongrád-Csanád, Hungary
| | - Klára Megyeri
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
| |
Collapse
|
|
4
|
Bhise N, Agarwal M, Thakur N, Akshay PS, Cherian S, Lole K. Repurposing of artesunate, an antimalarial drug, as a potential inhibitor of hepatitis E virus. Arch Virol 2023; 168:147. [PMID: 37115342 PMCID: PMC10141844 DOI: 10.1007/s00705-023-05770-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Accepted: 03/29/2023] [Indexed: 04/29/2023]
Abstract
Hepatitis E virus (HEV) is endemic in several developing countries of Africa and Asia. It mainly causes self-limiting waterborne infections, in either sporadic or outbreak form. Recently, HEV was shown to cause chronic infections in immunosuppressed individuals. Ribavirin and interferon, the current off-label treatment options for hepatitis E, have several side effects. Hence, there is a need for new drugs. We evaluated the antimalarial drug artesunate (ART) against genotype 1 HEV (HEV-1) and HEV-3 using a virus-replicon-based cell culture system. ART exhibited 59% and 43% inhibition of HEV-1 and HEV-3, respectively, at the highest nontoxic concentration. Computational molecular docking analysis showed that ART can bind to the helicase active site (affinity score, -7.4 kcal/mol), indicating its potential to affect ATP hydrolysis activity. An in vitro ATPase activity assay of the helicase indeed showed 24% and 55% inhibition at 19.5 µM (EC50) and 78 µM concentrations of ART, respectively. Since ATP is a substrate of RNA-dependent RNA polymerase (RdRp) as well, we evaluated the effect of ART on the enzymatic activity of the viral polymerase. Interestingly, ART showed 26% and 40% inhibition of the RdRp polymerase activity at 19.5 µM and 78 µM concentrations of ART, respectively. It could be concluded from these findings that ART inhibited replication of both HEV-1 and HEV-3 by directly targeting the activities of the viral enzymes helicase and RdRp. Considering that ART is known to be safe in pregnant women, we think this antimalarial drug deserves further evaluation in animal models.
Collapse
Affiliation(s)
- Neha Bhise
- Hepatitis Group, Indian Council of Medical Research-National Institute of Virology, Microbial Containment Complex, Pune, India
| | - Megha Agarwal
- Bioinformatics and Data Management Group, Indian Council of Medical Research-National Institute of Virology, Dr. Ambedkar Road, Pune, India
| | - Nidhi Thakur
- Hepatitis Group, Indian Council of Medical Research-National Institute of Virology, Microbial Containment Complex, Pune, India
| | - P S Akshay
- Hepatitis Group, Indian Council of Medical Research-National Institute of Virology, Microbial Containment Complex, Pune, India
| | - Sarah Cherian
- Bioinformatics and Data Management Group, ICMR-National Institute of Virology, 20-A, Dr. Ambedkar Road, Pune, 411001, India.
| | - Kavita Lole
- Hepatitis Group, ICMR-National Institute of Virology, Microbial Containment Complex, Sus Road, Pashan, Pune, 411021, India.
| |
Collapse
|
|
5
|
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.
Collapse
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
| |
Collapse
|
|
6
|
Zhou YH, Zhao H. Immunobiology and Host Response to HEV. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:93-118. [PMID: 37223861 DOI: 10.1007/978-981-99-1304-6_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Hepatitis E virus (HEV) usually causes acute self-limiting hepatitis but sometimes leads to chronic infection in immunocompromised persons. HEV is not directly cytopathic. Immunologically mediated events after HEV infection are believed to play important roles in the pathogenesis and clearance of infection. The anti-HEV antibody responses have been largely clarified since the determination of major antigenic determinant of HEV, which is located in the C-terminal portion of ORF2. This major antigenic determinant also forms the conformational neutralization epitopes. Robust anti-HEV immunoglobulin M (IgM) and IgG responses usually develop 3-4 weeks after infection in experimentally infected nonhuman primates. In humans, potent specific IgM and IgG responses occur in the very early phase of the disease and are critical in eliminating the virus, in concert with the innate and adaptive T-cell immune responses. Testing anti-HEV IgM is valuable in the diagnosis of acute hepatitis E. The long-term persistence and protection of anti-HEV IgG provide the basis for estimating the prevalence of HEV infection and for the development of a hepatitis E vaccine. Although human HEV has four genotypes, all the viral strains are considered to belong to a single serotype. It is becoming increasingly clear that the innate and adaptive T-cell immune responses play critical roles in the clearance of the virus. Potent and multispecific CD4+ and CD8+ T cell responses to the ORF2 protein occur in patients with acute hepatitis E, and weaker HEV-specific CD4+ and CD8+ T cell responses appear to be associated with chronic hepatitis E in immunocompromised individuals.
Collapse
Affiliation(s)
- Yi-Hua Zhou
- Departments of Experimental Medicine and Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Hong Zhao
- Department of Infectious Diseases, Second Hospital of Nanjing, Southeast University School of Medicine, Nanjing, China
| |
Collapse
|
|
7
|
Micro RNAs—The Small Big Players in Hepatitis E Virus Infection: A Comprehensive Review. Biomolecules 2022; 12:biom12111543. [PMID: 36358893 PMCID: PMC9687951 DOI: 10.3390/biom12111543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 10/17/2022] [Accepted: 10/19/2022] [Indexed: 12/02/2022] Open
Abstract
The molecular mechanism of hepatitis E virus (HEV) pathology is still unclear. The micro RNAs (miRNAs), of host or viral origin, interfere with virus replication and host environment in order to create an appropriate condition for the production of mature HEV progeny. Understanding the biogenesis and the interference of miRNAs with HEV will help to revile the mechanism of viral pathogenesis.
Collapse
|
|
8
|
Chen Z, Wei J, Jiang L, Ying D, Tian W, Zhang M, Wen G, Wang S, Liu C, Wang Y, Wu T, Tang Z, Zheng Z, Yan L, Xia N. Case Report: Chronic hepatitis E in a hematopoietic stem cell transplant recipient: The first report of hepatitis E virus genotype 4 causing chronic infection in a non-solid organ recipient. Front Immunol 2022; 13:954697. [PMID: 36275730 PMCID: PMC9581728 DOI: 10.3389/fimmu.2022.954697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 09/07/2022] [Indexed: 11/30/2022] Open
Abstract
Hepatitis E virus (HEV) is one of the most important public health issues around the world, and chronic HEV infection has been reported in immunosuppressed individuals. This study reported a male case, with very severe aplastic anemia (AA), who developed chronic hepatitis E after hematopoietic stem cell transplantation (HSCT). Abnormal alanine aminotransferase (ALT) appeared after HSCT and persisted for twenty-nine months. The case was seropositive for anti-HEV IgG and IgM after HSCT. Twenty-two months after HSCT, HEV RNA and antigen (Ag) testing were positive and persisted for five and seven months, respectively. Positive stains of HEV Ag were present in a liver biopsy sample. HEV Ag was present in bone marrow. The individual rapidly developed liver cirrhosis and was rescued by a regimen of oral ribavirin. These factors suggested there is a risk of HEV infection in HSCT recipients.
Collapse
Affiliation(s)
- Zihao Chen
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China
| | - Junfeng Wei
- Department of Infectious Diseases, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, China
| | - Li Jiang
- Department of Hematology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, China
| | - Dong Ying
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China
- School of Life Sciences, Xiamen University, Xiamen, China
| | - Weikun Tian
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China
- School of Life Sciences, Xiamen University, Xiamen, China
| | - Mengyang Zhang
- Department of Pathology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, China
| | - Guiping Wen
- United Diagnostic and Research Center for Clinical Genetics, Women and Children’s Hospital, School of Medicine and School of Public Health, Xiamen University, Xiamen, China
| | - Siling Wang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China
| | - Chang Liu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China
| | - Yingbin Wang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China
- Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, China
| | - Ting Wu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China
- Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, China
| | - Zimin Tang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China
- Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, China
- *Correspondence: Zimin Tang, ; Zizheng Zheng, ; Li Yan,
| | - Zizheng Zheng
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China
- Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, China
- *Correspondence: Zimin Tang, ; Zizheng Zheng, ; Li Yan,
| | - Li Yan
- Department of Severe Hepatology, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
- *Correspondence: Zimin Tang, ; Zizheng Zheng, ; Li Yan,
| | - Ningshao Xia
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China
- School of Life Sciences, Xiamen University, Xiamen, China
- Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, China
- Research Unit of Frontier Technology of Structural Vaccinology, Chinese Academy of Medical Sciences, Xiamen, China
| |
Collapse
|
|
9
|
Ma Z, de Man RA, Kamar N, Pan Q. Chronic hepatitis E: Advancing research and patient care. J Hepatol 2022; 77:1109-1123. [PMID: 35605741 DOI: 10.1016/j.jhep.2022.05.006] [Citation(s) in RCA: 72] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 05/08/2022] [Accepted: 05/10/2022] [Indexed: 12/15/2022]
Abstract
The hepatitis E virus (HEV) was initially thought to exclusively cause acute hepatitis. However, the first diagnosis of chronic hepatitis E in transplant recipients in 2008 profoundly changed our understanding of this pathogen. We have now begun to understand that specific HEV genotypes can cause chronic infection in certain immunocompromised populations. Over the past decade, dedicated clinical and experimental research has substantiated knowledge on the epidemiology, transmission routes, pathophysiological mechanisms, diagnosis, clinical features and treatment of chronic HEV infection. Nevertheless, many gaps and major challenges remain, particularly regarding the translation of knowledge into disease prevention and improvement of clinical outcomes. This article aims to highlight the latest developments in the understanding and management of chronic hepatitis E. More importantly, we attempt to identify major knowledge gaps and discuss strategies for further advancing both research and patient care.
Collapse
Affiliation(s)
- Zhongren Ma
- Biomedical Research Center, Northwest Minzu University, Lanzhou, China
| | - Robert A de Man
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands
| | - Nassim Kamar
- Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Disease (Infinity), University Paul Sabatier, Toulouse, France
| | - Qiuwei Pan
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
| |
Collapse
|
|
10
|
Ghandili S, Lindhauer C, Pischke S, zur Wiesch JS, von Kroge PH, Polywka S, Bokemeyer C, Fiedler W, Kröger N, Ayuk F, Adjallé R, Modemann F. Clinical features of hepatitis E infections in patients with hematologic disorders. Haematologica 2022; 107:2870-2883. [PMID: 35770534 PMCID: PMC9713558 DOI: 10.3324/haematol.2022.280853] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Indexed: 12/14/2022] Open
Abstract
Hepatitis E virus is increasingly being reported to cause chronic infection in immunocompromised patients. However, less is known about patients with an underlying hematologic disease. In particular, the impact of hepatitis E infection on oncological therapy has been poorly described. In this retrospective single-center study, we analyzed 35 hematologic patients with hepatitis E, including 20 patients under active oncological treatment and 15 patients who were in the posttreatment follow-up or under active surveillance. The primary aim was to describe the clinical courses with particular focus on any hepatitis E-related therapy modifications of cancer-directed therapy. In the majority (60%) of patients who were under active oncological treatment, hepatitis E-related therapy modifications were made, and 25% of deaths were due to progression of the hematologic disease. In patients receiving concomitant oncological treatment, no hepatitis Erelated deaths occurred. In contrast, two patients in the follow-up group died from hepatitis E-associated acute-onchronic liver failure. Chronic hepatitis E was observed in 34% of all cases and 43% received ribavirin therapy; of those, 27% achieved a sustained virological response. CD20-directed therapy was the only independent risk factor for developing chronic hepatitis E. We conclude that CD20-directed treatment at any time point is a risk factor for developing chronic hepatitis E. Nevertheless, since mortality from the progression of hematologic disease was higher than hepatitis E-related mortality, we suggest careful case-by-case decisions on modifications of cancer treatment. Patients in the posttreatment follow-up phase may also suffer from severe courses and hepatitis E chronicity occurs as frequently as in patients undergoing active therapy.
Collapse
Affiliation(s)
- Susanne Ghandili
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf,*SG and CL contributed equally as co-first authors
| | - Cecilia Lindhauer
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf,*SG and CL contributed equally as co-first authors
| | - Sven Pischke
- The I. Department of Internal Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf
| | - Julian Schulze zur Wiesch
- The I. Department of Internal Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf
| | - Philipp H. von Kroge
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf
| | - Susanne Polywka
- The Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf
| | - Carsten Bokemeyer
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf
| | - Walter Fiedler
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf
| | - Nicolaus Kröger
- Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf and
| | - Francis Ayuk
- Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf and
| | - Raissa Adjallé
- Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf and ,RA and FM contributed equally as co-last authors
| | - Franziska Modemann
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf,Mildred Scheel Cancer Career Center, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany,RA and FM contributed equally as co-last authors
| |
Collapse
|
|
11
|
Damiris K, Aghaie Meybodi M, Niazi M, Pyrsopoulos N. Hepatitis E in immunocompromised individuals. World J Hepatol 2022; 14:482-494. [PMID: 35582299 PMCID: PMC9055194 DOI: 10.4254/wjh.v14.i3.482] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/15/2021] [Accepted: 02/12/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) originally identified as a cause of acute icteric hepatitis in developing countries has grown to be a cause of zoonotic viral hepatitis in developed countries such as the United States. While there are eight identified genotypes to date, genotype 1 (HEV1), HEV2, HEV3, HEV4 are the most common to infect humans. HEV1 and HEV2 are most common in developing countries including Latina America, Africa and Asia, and are commonly transmitted through contaminated water supplies leading to regional outbreaks. In contrast HEV3 and HEV4 circulate freely in many mammalian animals and can lead to occasional transmission to humans through fecal contamination or consumption of undercooked meat. The incidence and prevalence of HEV in the United States is undetermined given the absence of FDA approved serological assays and the lack of commercially available testing. In majority of cases, HEV infection is a self-limiting hepatitis requiring only symptomatic treatment. However, this is not the case in immunocompromised individuals, including those that have undergone solid organ or stem cell transplantation. In this subset of patients, chronic infection can be life threatening as hepatic insult can lead to inflammation and fibrosis with subsequent cirrhosis and death. The need for re-transplantation as a result of post-transplant hepatitis is of great concern. In addition, there have been many reported incidents of extrahepatic manifestations, for which the exact mechanisms remain to be elucidated. The cornerstone of treatment in immunocompromised solid organ transplant recipients is reduction of immunosuppressive therapies, while attempting to minimize the risk of organ rejection. Subsequent treatment options include ribavirin, and pegylated interferon alpha in those who have demonstrated ribavirin resistance. Further investigation assessing safety and efficacy of anti-viral therapy is imperative given the rising global health burden. Given this concern, vaccination has been approved in China with other investigations underway throughout the world. In this review we introduce the epidemiology, diagnosis, clinical manifestations, and treatment of HEV, with emphasis on immunocompromised individuals in the United States.
Collapse
Affiliation(s)
- Konstantinos Damiris
- Department of Medicine, Rutgers - New Jersey Medical School, Newark, NJ 07103, United States.
| | - Mohamad Aghaie Meybodi
- Department of Medicine, Rutgers - New Jersey Medical School, Newark, NJ 07103, United States
| | - Mumtaz Niazi
- Department of Medicine - Gastroenterology and Hepatology, Rutgers - New Jersey Medical School, Newark, NJ 07103, United States
| | - Nikolaos Pyrsopoulos
- Department of Medicine - Gastroenterology and Hepatology, Rutgers - New Jersey Medical School, Newark, NJ 07103, United States
| |
Collapse
|
|
12
|
Liang Z, Shu J, He Q, Zhang F, Dai L, Wang L, Lu F, Wang L. High dose sofosbuvir and sofosbuvir-plus-ribavirin therapy inhibit Hepatitis E Virus (HEV) replication in a rabbit model for acute HEV infection. Antiviral Res 2022; 199:105274. [PMID: 35247472 DOI: 10.1016/j.antiviral.2022.105274] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 02/23/2022] [Accepted: 02/28/2022] [Indexed: 12/14/2022]
Abstract
Hepatitis E virus (HEV) is an important cause of viral hepatitis worldwide and there is currently no FDA-approved anti-HEV drug. The commonly used drug ribavirin (RBV) could not achieve viral clearance in all patients and can induce drug resistance. Recent studies showed sofosbuvir (SOF) can inhibit HEV replication in vitro and has add-on effect when combined with RBV, but the effect of SOF against HEV infection remains controversial and the dosage of SOF warrants further exploration. In this study, a rabbit model for acute HEV infection was used to evaluate the effect of SOF at different doses against HEV genotype 3 and 4, and to compare the antiviral effect of SOF-plus-RBV therapy with RBV monotherapy. Virological parameters on fecal, serological and intrahepatic level were tested by real-time PCR and ELISA. Liver function tests and histopathological assays were performed. Both 200 mg/d and 300 mg/d SOF treatment inhibits HEV replication with relieved liver inflammation and declined levels of fecal HEV RNA, viremia and antigenemia. 300 mg/d SOF eliminated HEV replication while a short viral rebound was observed after 200 mg/d SOF treatment. The SOF-plus-RBV therapy also showed stronger anti-HEV effect than RBV monotherapy. Our study suggests that high dose of SOF showed better anti-HEV effect in the rabbit model. Moreover, the de novo SOF-plus-RBV therapy which eliminated acute HEV infection more efficiently than RBV monotherapy may serve as an alternative treatment strategy.
Collapse
Affiliation(s)
- Zhaochao Liang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Jingyi Shu
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Qiyu He
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Fan Zhang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Lizhong Dai
- Peking University-Sansure Biotech Joint Laboratory of Molecular Medicine, Peking University, Beijing, China
| | - Ling Wang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
| | - Fengmin Lu
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; Peking University-Sansure Biotech Joint Laboratory of Molecular Medicine, Peking University, Beijing, China.
| | - Lin Wang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; Peking University-Sansure Biotech Joint Laboratory of Molecular Medicine, Peking University, Beijing, China.
| |
Collapse
|
|
13
|
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.
Collapse
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
| |
Collapse
|
|
14
|
Mechanism of Cross-Species Transmission, Adaptive Evolution and Pathogenesis of Hepatitis E Virus. Viruses 2021; 13:v13050909. [PMID: 34069006 PMCID: PMC8157021 DOI: 10.3390/v13050909] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 05/12/2021] [Accepted: 05/13/2021] [Indexed: 12/17/2022] Open
Abstract
Hepatitis E virus (HEV) is the leading cause of acute hepatitis worldwide. While the transmission in developing countries is dominated by fecal-oral route via drinking contaminated water, the zoonotic transmission is the major route of HEV infection in industrialized countries. The discovery of new HEV strains in a growing number of animal species poses a risk to zoonotic infection. However, the exact mechanism and the determinant factors of zoonotic infection are not completely understood. This review will discuss the current knowledge on the mechanism of cross-species transmission of HEV infection, including viral determinants, such as the open reading frames (ORFs), codon usage and adaptive evolution, as well as host determinants, such as host cellular factors and the host immune status, which possibly play pivotal roles during this event. The pathogenesis of hepatitis E infection will be briefly discussed, including the special forms of this disease, including extrahepatic manifestations, chronic infection, and fulminant hepatitis in pregnant women.
Collapse
|
|
15
|
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
|
|
16
|
Rathi S, Duseja A, Thakur V, Ratho RK, Singh MP, Taneja S, Das A, Aggarwal R, Dhiman RK, Chawla YK. Chronic Hepatitis E With Genotype 1-Masquerading as Allograft Rejection After LiverTransplantation. J Clin Exp Hepatol 2021; 11:400-403. [PMID: 33994721 PMCID: PMC8103309 DOI: 10.1016/j.jceh.2020.07.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 07/12/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatitis E is one of the leading causes of acute viral hepatitis worldwide. Chronic infection with hepatitis E is less common and limited to immunosuppressed patients and is usually due to genotype 3 of the virus. Genotype 1, the most prevalent strain in the South Asian region, is seldom known to be associated with chronic hepatitis. Here we describe a case of chronic hepatitis E with genotype 1 in a post-liver transplant setting. In the index case, previously compensated cryptogenic cirrhosis was decompensated by an acute hepatitis E infection, which necessitated liver transplantation because of acute chronic liver failure. This later progressed to chronicity. This case may have significant implications in management, especially in the post-liver transplant setting.
Collapse
Affiliation(s)
- Sahaj Rathi
- Department of Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India,Address for correspondence. Dr Ajay Duseja, MD, DM, FAMS, FAASLD, FACG, FSGEI, Professor, Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, Sector 12, 160012, India. Tel.: +91 172 2754793; Fax: +91 172 2744401.
| | - Vikram Thakur
- Department of Virology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Radha K. Ratho
- Department of Virology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Mini P. Singh
- Department of Virology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Ashim Das
- Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Science (SGPGI), Lucknow, Uttar Pradesh, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Yogesh K. Chawla
- Department of Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| |
Collapse
|
|
17
|
Capai L, Hozé N, Chiaroni J, Gross S, Djoudi R, Charrel R, Izopet J, Bosseur F, Priet S, Cauchemez S, de Lamballerie X, Falchi A, Gallian P. Seroprevalence of hepatitis E virus among blood donors on Corsica, France, 2017. ACTA ACUST UNITED AC 2020; 25. [PMID: 32046820 PMCID: PMC7014670 DOI: 10.2807/1560-7917.es.2020.25.5.1900336] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Background Hepatitis E virus (HEV) is an emerging zoonotic pathogen and an important cause of acute viral hepatitis in European countries. Corsica Island has been previously identified as a hyperendemic area for HEV. Aim Our aim was to characterise the prevalence and titres of IgG antibodies to HEV among blood donors on Corsica and establish a model of the annual force of infection. Methods Between September 2017 and January 2018, 2,705 blood donations were tested for anti-HEV IgG using the Wantai HEV IgG enzyme immunoassay. Results The overall seroprevalence was 56.1%. In multivariate analysis, seroprevalence was higher in men than in women (60.0% vs 52.2%; p < 0.01), increased with age and was significantly higher among donors born on Corsica (60.6% vs 53.2%; p < 0.01). No significant difference was observed between the five districts of the island. IgG anti-HEV titres were mostly low (70% of positive donors had titres < 3 IU/mL). In Corsican natives, increasing seroprevalence by age could be explained by models capturing a loss of immunity (annual probability of infection: 4.5%; duration of immunity: 55 years) or by age-specific probabilities of infection (3.8% for children, 1.3% for adults). Conclusion We confirmed the high HEV seroprevalence on Corsica and identified three aspects that should be further explored: (i) the epidemiology in those younger than 18 years, (ii) common sources of contamination, in particular drinking water, that may explain the wide exposure of the population, and (iii) the actual protection afforded by the low IgG titres observed and the potential susceptibility to secondary HEV infection.
Collapse
Affiliation(s)
- Lisandru Capai
- EA 7310, Laboratoire de Virologie, Université de Corse, Corte, France
| | - Nathanaël Hozé
- Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, UMR2000, CNRS, Paris, France
| | - Jacques Chiaroni
- Etablissement Français du Sang Provence alpes Côte d'Azur et Corse, Marseille, France
| | - Sylvie Gross
- Etablissement Français du Sang, 93210, La Plaine-Saint-Denis, France
| | - Rachid Djoudi
- Etablissement Français du Sang, 93210, La Plaine-Saint-Denis, France
| | - Rémi Charrel
- Unité des Virus Émergents (UVE): Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France
| | - Jacques Izopet
- Institut National de la Santé et de la Recherche Médicale Unité 1043, Université Toulouse III, Toulouse, France.,Laboratoire de Virologie, Institut Fédératif de Biologie, Centre Hospitalier et Universitaire, Toulouse, France
| | - Frédéric Bosseur
- Sciences Pour l'Environnement - UMR CNRS 6134 Université de Corse, Corte, France
| | - Stéphane Priet
- Unité des Virus Émergents (UVE): Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France
| | - Simon Cauchemez
- Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, UMR2000, CNRS, Paris, France
| | - Xavier de Lamballerie
- Unité des Virus Émergents (UVE): Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France
| | - Alessandra Falchi
- EA 7310, Laboratoire de Virologie, Université de Corse, Corte, France
| | - Pierre Gallian
- Unité des Virus Émergents (UVE): Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.,Etablissement Français du Sang, 93210, La Plaine-Saint-Denis, France.,Etablissement Français du Sang Provence alpes Côte d'Azur et Corse, Marseille, France
| |
Collapse
|
|
18
|
Aslan AT, Balaban HY. Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment. World J Gastroenterol 2020; 26:5543-5560. [PMID: 33071523 PMCID: PMC7545399 DOI: 10.3748/wjg.v26.i37.5543] [Citation(s) in RCA: 107] [Impact Index Per Article: 21.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 08/11/2020] [Accepted: 09/09/2020] [Indexed: 02/06/2023] Open
Abstract
The hepatitis E virus (HEV) is the fifth known form of viral hepatitis and was first recognized as the cause of an epidemic of unexplained acute hepatitis in the early 1980s. Globally, it is one of the most frequent causes of acute viral hepatitis. The majority of HEV infections are asymptomatic and lead to the spontaneous clearance of the virus. Among the eight different genotypes identified to date, HEV genotype 1 (HEV1), HEV2, HEV3, and HEV4 are the most frequent genotypes causing infections in humans. HEV1 and HEV2 are prevalent in developing regions and able to result in large-scale outbreaks originating from contaminated water supplies. They are also responsible for severe hepatitis in pregnant patients and infants. In contrast, HEV3 and HEV4 are zoonotic, and the transmission of these genotypes to humans occurs mainly through the fecal contamination of water and consumption of contaminated meat from infected animals. Their main reservoir is the pig, and they are mostly encountered in developed countries. The major risk groups for HEV infection and its ensuing adverse consequences are pregnant women, infants, older people, immunocompromised individuals, patients with underlying chronic liver diseases, and workers that come into close contact with HEV-infected animals. In the clinical perspective, HEV infections have diverse clinical manifestations including acute and self-limiting hepatitis, acute-on-chronic liver disease, chronic hepatitis, cirrhosis, and liver failure. Although HEV mainly results in acute self-limiting infection, chronic HEV infection may occur among immunocompromised patients (e.g., solid-organ transplant recipients). Additionally, HEV-associated extrahepatic manifestations involving various organs have been reported in the last decade, although the causal link for many of them still needs to be proven. Ribavirin and interferon-alpha are the most widely used agents for the treatment of HEV infections with a certain level of success. However, ribavirin is contraindicated in pregnant patients, and interferon-alpha cannot be used in most transplant recipients. Therefore, there is an urgent need for novel antiviral compounds that are safe and effective particularly for patients having contraindications for ribavirin or interferon-alpha and infected by the ribavirin-resistant HEV. In this review article, a literature search using PubMed and MEDLINE databases was performed, up to March 2020. Only the articles published in English were reviewed.
Collapse
Affiliation(s)
| | - Hatice Yasemin Balaban
- Department of Gastroenterology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey
| |
Collapse
|
|
19
|
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.
Collapse
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
| |
Collapse
|
|
20
|
Field Z, Russin M, Murillo Alvarez RM, Madruga M, Carlan S. Acute Hepatitis E: A Rare Cause of Acute Liver Failure in a Patient With Acute Myeloid Leukemia. Cureus 2020; 12:e10628. [PMID: 33123441 PMCID: PMC7584302 DOI: 10.7759/cureus.10628] [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: 07/02/2020] [Accepted: 09/24/2020] [Indexed: 11/05/2022] Open
Abstract
Immunocompromised patients are particularly at risk to develop hepatitis E virus (HEV) infection and its related complications. We present a rare case of HEV infection in a 35-year-old Hispanic female with concomitant acute myeloid leukemia (AML). The patient presented with acute liver failure within a few weeks after receiving a blood transfusion. Our case likely represented an acute de novo HEV infection after chemotherapy in a patient with concurrent AML, evidenced by the presence of anti-HEV IgM antibodies as well as histological findings, and with a previous history of recent transfusions being one of the strongest risk factors for transmission. Liver failure from an acute de novo hepatitis E infection with concurrent AML can be catastrophic in the immunosuppressed patient. Our case is particularly unique due to the uncommon presentation of acute hepatitis E in a non-pregnant reproductive aged Hispanic female with recently diagnosed AML. Clinicians should maintain a low threshold to test serum HEV-RNA if a patient presents with signs and symptoms suggestive of acute hepatitis.
Collapse
Affiliation(s)
- Zachary Field
- Internal Medicine, Orlando Regional Medical Center, Orlando, USA
| | - Michelle Russin
- Internal Medicine, Orlando Regional Medical Center, Orlando, USA
| | | | - Mario Madruga
- Internal Medicine, Orlando Regional Medical Center, Orlando, USA
| | - Steve Carlan
- Obstetrics and Gynecology, Orlando Regional Medical Center, Orlando, USA
| |
Collapse
|
|
21
|
Kitaura S, Wakabayashi Y, Okazaki A, Okada Y, Okamoto K, Ikeda M, Okugawa S, Moriya K. The First Case Report of Acute Symptomatic HEV Genotype 4 Infection in an HIV-positive Patient in Japan. Intern Med 2020; 59:1655-1658. [PMID: 32269193 PMCID: PMC7402963 DOI: 10.2169/internalmedicine.4505-20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Hepatitis E virus (HEV) is a common cause of acute hepatitis. Four major genotypes of HEV have been studied, with genotype 4 being the predominant genotype across Asia. We herein describe the case of a 50-year-old man with a history of human immunodeficiency virus (HIV) infection who was admitted with acute transaminitis. Serum anti-HEV-IgA and HEV-RNA were detected at the time of presentation and further testing revealed HEV genotype 4. To the best of our knowledge, this represents the first clinical case report of acute symptomatic HEV genotype 4 infection in an HIV-positive patient in Japan.
Collapse
Affiliation(s)
- Satoshi Kitaura
- Department of Infectious Diseases, The University of Tokyo Hospital, Japan
| | - Yoshitaka Wakabayashi
- Department of Infectious Diseases, The University of Tokyo Hospital, Japan
- Department of Internal Medicine, Teikyo University, Japan
| | - Aiko Okazaki
- Department of Infectious Diseases, The University of Tokyo Hospital, Japan
| | - Yuta Okada
- Department of Infectious Diseases, The University of Tokyo Hospital, Japan
| | - Koh Okamoto
- Department of Infectious Diseases, The University of Tokyo Hospital, Japan
| | - Mahoko Ikeda
- Department of Infection Control and Prevention, The University of Tokyo, Japan
| | - Shu Okugawa
- Department of Infectious Diseases, The University of Tokyo Hospital, Japan
| | - Kyoji Moriya
- Department of Infectious Diseases, The University of Tokyo Hospital, Japan
- Department of Infection Control and Prevention, The University of Tokyo, Japan
| |
Collapse
|
|
22
|
Abstract
BACKGROUND Hepatitis E virus (HEV) generally causes self-limiting viral hepatitis. However, in pregnant women, HEV infection can be severe and has been associated with up to 30% mortality in the third trimester. Additionally, HEV infection in pregnancy is also associated with high rates of preterm labor and vertical transmission. MAIN BODY HEV is now recognized as a global health problem in both developing and industrialized countries. HEV can be transmitted via the fecal-oral route, zoonotic route, and blood transfusion route. An altered immune status, hormonal levels, and viral factors may be related to the severity of the disease. Currently, no established treatment is available for HEV in pregnant women. A Chinese vaccine has been demonstrated to be protective against HEV in the general population and seems to be safe in pregnancy; however, its safety and efficacy in a large population of pregnant women remain to be determined. CONCLUSION This review summarizes the current knowledge about HEV infection during pregnancy and focuses on the epidemiology, clinical manifestations, mechanisms underlying severe liver injury, and management and prevention of HEV infection during pregnancy. Considering that HEV infection during pregnancy may result in poor outcomes, screening for and monitoring HEV infection early in pregnancy should be taken into account. In addition, a better understanding of the pathogenesis will help to develop potential treatment strategies targeting HEV infection in pregnancy.
Collapse
Affiliation(s)
- Chunchen Wu
- Department of Laboratory Medicine, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People's Republic of China
| | - Xiaoxue Wu
- Department of Laboratory Medicine, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People's Republic of China
| | - Jianbo Xia
- Department of Laboratory Medicine, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People's Republic of China.
| |
Collapse
|
|
23
|
Komolmit P, Oranrap V, Suksawatamnuay S, Thanapirom K, Sriphoosanaphan S, Srisoonthorn N, Posuwan N, Thongmee T, Treeprasertsuk S, Poovorawan Y. Clinical significance of post-liver transplant hepatitis E seropositivity in high prevalence area of hepatitis E genotype 3: a prospective study. Sci Rep 2020; 10:7352. [PMID: 32355268 PMCID: PMC7192897 DOI: 10.1038/s41598-020-64551-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 04/15/2020] [Indexed: 12/25/2022] Open
Abstract
High hepatitis E (HEV) seroprevalence has been reported in the general population and in post-liver transplant (LT) cases in several regions, including Thailand, with genotype 3 being a predominant genotype. We hypothesized that HEV might persist at a subclinical level and might pose clinical risks in the post-LT period. We performed a cross-sectional study with 108 post-LT patients and found an IgG seroprevalence of 55.6%. Subsequently, 91 cases without clinical evidence of HEV-related hepatitis were enrolled in 1 year of prospective follow-up to determine clinical status, serologies and serum/feces HEV RNA every 4 months. HEV RNA was detected, indicating subclinical infections in patients with or without seropositivity, with an annual incidence of 7.7%. Our results suggest that subclinical HEV infection exists among LT patients in this high-prevalence area. Thus, clinicians should be aware of the possibility of disease reemergence and HEV viral transmission in LT patients.
Collapse
Affiliation(s)
- Piyawat Komolmit
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
- The Research Unit of Hepatic Fibrosis and Cirrhosis, Department of Medicine, Chulalongkorn University, Bangkok, Thailand.
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
| | - Vinita Oranrap
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sirinporn Suksawatamnuay
- The Research Unit of Hepatic Fibrosis and Cirrhosis, Department of Medicine, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Kessarin Thanapirom
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- The Research Unit of Hepatic Fibrosis and Cirrhosis, Department of Medicine, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Supachaya Sriphoosanaphan
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Nunthiya Srisoonthorn
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Nawarat Posuwan
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Thanunrat Thongmee
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Yong Poovorawan
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| |
Collapse
|
|
24
|
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.
Collapse
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
| |
Collapse
|
|
25
|
Hoan NX, Huy PX, Sy BT, Meyer CG, Son TV, Binh MT, Giang DP, Tu Anh D, Bock CT, Wang B, Tong HV, Kremsner PG, Song LH, Toan NL, Velavan TP. High Hepatitis E virus (HEV) Positivity Among Domestic Pigs and Risk of HEV Infection of Individuals Occupationally Exposed to Pigs and Pork Meat in Hanoi, Vietnam. Open Forum Infect Dis 2019; 6:ofz306. [PMID: 31660396 PMCID: PMC6735913 DOI: 10.1093/ofid/ofz306] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 06/25/2019] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) infection can occur through consumption of undercooked pork meat or exposure to animal feces. Because there are scarce data only in developing countries, we assessed whether pigs might be a potential source of human HEV infections in Vietnam. In addition, we determined anti-HEV seroprevalences in the general population and in individuals professionally exposed to pigs and pork meat. METHODS The study took place in Hanoi, Vietnam. Liver tissues from domestic pigs (n = 210) and serum samples obtained from individuals occupationally exposed to pigs and pork meat (n = 283) and from unexposed healthy controls (n = 168) were screened for HEV-ribonucleic acid (RNA) by reverse-transcription polymerase chain reaction. The exposed group was divided into pork meat vendors (n = 81), pig farmers (n = 96), and slaughterers (n = 106). Serum samples were subjected to HEV immunoglobulin (Ig)G and IgM enzyme-linked immunosorbent assays. The HEV genotypes were assessed by direct sequencing, followed by phylogenetic analyses. RESULTS Hepatitis E virus seroprevalence was higher among persons occupationally exposed to pigs/pork meat compared with unexposed individuals (anti-HEV IgM 11% vs 6%, P = .07; anti-HEV IgG 53% vs 31%, P < .0001). Positivity of anti-HEV IgG among slaughterhouse staff was 66%, followed by 51% in pig-farmers and 38% in pork meat vendors (P = .00073). A similar trend was observed for IgM positivity. Of the pig liver tissues, 26 of 210 (12.4%) were positive for HEV-RNA and assessed to be HEV genotype 3. CONCLUSIONS Hepatitis E virus circulates in domestic pigs in Hanoi and constitutes a permanent zoonotic disease risk. The high HEV seroprevalence among occupationally exposed individuals indicates an associated risk of HEV infection.
Collapse
Affiliation(s)
- Nghiem Xuan Hoan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Institute of Clinical Infectious Diseases, Hanoi, Vietnam
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
| | - Pham Xuan Huy
- Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam
| | - Bui Tien Sy
- Institute of Clinical Infectious Diseases, Hanoi, Vietnam
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
| | - Christian G Meyer
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
- Duy Tan University, Da Nang, Vietnam
| | - Trinh Van Son
- Institute of Clinical Infectious Diseases, Hanoi, Vietnam
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
| | - Mai Thanh Binh
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
| | - Dao Phuong Giang
- Institute of Clinical Infectious Diseases, Hanoi, Vietnam
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
| | - Dam Tu Anh
- Department of Immunology and Pathophysiology, Hanoi Medical University, Vietnam
| | - C-Thomas Bock
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
| | - Bo Wang
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
| | - Hoang Van Tong
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
- Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam
| | - Peter G Kremsner
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - Le Huu Song
- Institute of Clinical Infectious Diseases, Hanoi, Vietnam
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
| | - Nguyen Linh Toan
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
- Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam
| | - Thirumalaisamy P Velavan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Medical Research, Hanoi, Vietnam
- Duy Tan University, Da Nang, Vietnam
| |
Collapse
|
|
26
|
Parisi F, Mazzei M, Verin R, Forzan M, Rocchigiani G, Roper C, Bertelloni G, Poli A. Hepatitis E virus infection in wild rabbit (Oryctolagus cuniculus) in Italy and in the UK: a serological, molecular, and pathological study. EUR J WILDLIFE RES 2019. [DOI: 10.1007/s10344-019-1314-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
|
|
27
|
Hartard C, Gantzer C, Bronowicki JP, Schvoerer E. Emerging hepatitis E virus compared with hepatitis A virus: A new sanitary challenge. Rev Med Virol 2019; 29:e2078. [PMID: 31456241 DOI: 10.1002/rmv.2078] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2019] [Revised: 07/19/2019] [Accepted: 07/22/2019] [Indexed: 12/21/2022]
Abstract
Hepatitis A (HAV) and E (HEV) viruses are able to cause liver disease in humans. Among the five classical hepatotropic viruses, they are mainly transmitted via the fecal-oral route. Historically, many similarities have thus been described between them according to their incidence and their pathogenicity, especially in countries with poor sanitary conditions. However, recent advances have provided new insights, and the gap is widening between them. Indeed, while HAV infection incidence tends to decrease in developed countries along with public health improvement, HEV is currently considered as an underdiagnosed emerging pathogen. HEV autochthonous infections are increasingly observed and are mainly associated with zoonotic transmissions. Extra hepatic signs resulting in neurological or renal impairments have also been reported for HEV, as well as a chronic carrier state in immunocompromised patients, arguing in favor of differential pathogenesis between those two viruses. Recent molecular tools have allowed studies of viral genome variability and investigation of links between viral plasticity and clinical evolution. The identification of key functional mutations in viral genomes may improve the knowledge of their clinical impact and is analyzed in depth in the present review.
Collapse
Affiliation(s)
- Cédric Hartard
- Laboratoire de Virologie, CHRU de Nancy Brabois, Vandœuvre-lès-Nancy, France.,Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), UMR 7564, Vandoeuvre-lès-Nancy, France.,CNRS, LCPME UMR 7564, Nancy, France.,Faculté des Sciences et Technologies, Institut Jean Barriol, Université de Lorraine, Vandœuvre-lès-Nancy, France
| | - Christophe Gantzer
- Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), UMR 7564, Vandoeuvre-lès-Nancy, France.,CNRS, LCPME UMR 7564, Nancy, France.,Faculté des Sciences et Technologies, Institut Jean Barriol, Université de Lorraine, Vandœuvre-lès-Nancy, France
| | | | - Evelyne Schvoerer
- Laboratoire de Virologie, CHRU de Nancy Brabois, Vandœuvre-lès-Nancy, France.,Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), UMR 7564, Vandoeuvre-lès-Nancy, France.,CNRS, LCPME UMR 7564, Nancy, France.,Faculté des Sciences et Technologies, Institut Jean Barriol, Université de Lorraine, Vandœuvre-lès-Nancy, France
| |
Collapse
|
|
28
|
Kamar N, Pischke S. Acute and Persistent Hepatitis E Virus Genotype 3 and 4 Infection: Clinical Features, Pathogenesis, and Treatment. Cold Spring Harb Perspect Med 2019; 9:cshperspect.a031872. [PMID: 29735575 DOI: 10.1101/cshperspect.a031872] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Hepatitis E virus (HEV) genotype (gt)3 and 4 infections are prevalent in industrialized and high-income countries. Although most HEV gt3 and gt4 infections are clinically silent, acute infection may be symptomatic in some patients. In persons with underlying liver disease and in elderly men, HEV infections may present as acute or acute-on-chronic liver failure. Chronic hepatitis may develop in immunosuppressed individuals, including transplant recipients, human immunodeficiency virus (HIV)-infected patients, and persons with hematologic malignancy undergoing chemotherapy, and may progress to life-threatening liver cirrhosis. Extrahepatic manifestations of infection may include neurological and renal disease. Although there is no approved specific therapy for the treatment of acute or chronic HEV gt3 or gt4 infection, off-label use of ribavirin appears to be capable of eliminating chronic HEV infection, and may reduce disease severity in patients suffering from acute liver failure.
Collapse
Affiliation(s)
- Nassim Kamar
- Department of Nephrology and Organ Transplantation, Université Paul Sabatier, Toulouse 31059, France
| | - Sven Pischke
- Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany
| |
Collapse
|
|
29
|
Primadharsini PP, Nagashima S, Okamoto H. Genetic Variability and Evolution of Hepatitis E Virus. Viruses 2019; 11:E456. [PMID: 31109076 PMCID: PMC6563261 DOI: 10.3390/v11050456] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 05/15/2019] [Accepted: 05/16/2019] [Indexed: 12/16/2022] Open
Abstract
Hepatitis E virus (HEV) is a single-stranded positive-sense RNA virus. HEV can cause both acute and chronic hepatitis, with the latter usually occurring in immunocompromised patients. Modes of transmission range from the classic fecal-oral route or zoonotic route, to relatively recently recognized but increasingly common routes, such as via the transfusion of blood products or organ transplantation. Extrahepatic manifestations, such as neurological, kidney and hematological abnormalities, have been documented in some limited cases, typically in patients with immune suppression. HEV has demonstrated extensive genomic diversity and a variety of HEV strains have been identified worldwide from human populations as well as growing numbers of animal species. The genetic variability and constant evolution of HEV contribute to its physiopathogenesis and adaptation to new hosts. This review describes the recent classification of the Hepeviridae family, global genotype distribution, clinical significance of HEV genotype and genomic variability and evolution of HEV.
Collapse
Affiliation(s)
- Putu Prathiwi Primadharsini
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi 329-0498, Japan.
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi 329-0498, Japan.
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi 329-0498, Japan.
| |
Collapse
|
|
30
|
Narayanan S, Abutaleb A, Sherman KE, Kottilil S. Clinical features and determinants of chronicity in hepatitis E virus infection. J Viral Hepat 2019; 26:414-421. [PMID: 30636092 PMCID: PMC6437685 DOI: 10.1111/jvh.13059] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Accepted: 10/25/2018] [Indexed: 12/19/2022]
Abstract
Hepatitis E virus (HEV) has traditionally been associated with an acute, self-limiting hepatitis and is not known to have any chronic sequelae. HEV genotypes 1 and 2, which are human pathogens, have been associated with this self-limiting presentation, in both sporadic and epidemic settings. HEV genotype 3, which is zoonotically transmitted, is increasingly being reported as a cause of chronic infection in immunocompromised patients. These include patients with solid organ transplants, patients receiving chemotherapy for haematologic malignancies and patients infected with HIV. Chronic infection is associated with rapidly progressing liver disease and extrahepatic manifestations including neurologic disorders. We review the clinical manifestations of chronic HEV infection and discuss factors determining persistence and chronicity of HEV.
Collapse
Affiliation(s)
- Shivakumar Narayanan
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, Baltimore, Maryland
| | - Ameer Abutaleb
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, Baltimore, Maryland,Division of Gastroenterology & Hepatology, University of Maryland, Baltimore, Maryland
| | - Kenneth E. Sherman
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, Ohio
| | - Shyam Kottilil
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, Baltimore, Maryland
| |
Collapse
|
|
31
|
Sridhar S, Cheng VCC, Wong SC, Yip CCY, Wu S, Lo AWI, Leung KH, Mak WWN, Cai J, Li X, Chan JFW, Lau SKP, Woo PCY, Lai WM, Kwan TH, Au TWK, Lo CM, Wong SCY, Yuen KY. Donor-Derived Genotype 4 Hepatitis E Virus Infection, Hong Kong, China, 2018. Emerg Infect Dis 2019; 25:425-433. [PMID: 30789146 PMCID: PMC6390757 DOI: 10.3201/eid2503.181563] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Hepatitis E virus (HEV) genotype 4 (HEV-4) is an emerging cause of acute hepatitis in China. Less is known about the clinical characteristics and natural history of HEV-4 than HEV genotype 3 infections in immunocompromised patients. We report transmission of HEV-4 from a deceased organ donor to 5 transplant recipients. The donor had been viremic but HEV IgM and IgG seronegative, and liver function test results were within reference ranges. After a mean of 52 days after transplantation, hepatitis developed in all 5 recipients; in the liver graft recipient, disease was severe and with progressive portal hypertension. Despite reduced immunosuppression, all HEV-4 infections progressed to persistent hepatitis. Four patients received ribavirin and showed evidence of response after 2 months. This study highlights the role of organ donation in HEV transmission, provides additional data on the natural history of HEV-4 infection, and points out differences between genotype 3 and 4 infections in immunocompromised patients.
Collapse
|
|
32
|
Meta-Analysis of Human IgG anti-HEV Seroprevalence in Industrialized Countries and a Review of Literature. Viruses 2019; 11:v11010084. [PMID: 30669517 PMCID: PMC6357031 DOI: 10.3390/v11010084] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 01/16/2019] [Accepted: 01/18/2019] [Indexed: 12/11/2022] Open
Abstract
Although Hepatitis E is increasingly described as a major cause of liver disease in industrialized countries, the epidemiology is far from being fully elucidated. We provide here a comprehensive review of documented clusters of cases, and of serological studies conducted in populations with distinct types of exposure. Seroprevalence rates range from <5% to >50% depending on the countries and the groups of population. Such discrepancies can be attributed to the type of serological assay used, but this solves only a part of the problem. We performed a meta-analysis of studies performed with the broadly used Wantai HEV-IgG ELISA and found striking differences that remain difficult to understand with the current knowledge of transmission pathways.
Collapse
|
|
33
|
Meister TL, Bruening J, Todt D, Steinmann E. Cell culture systems for the study of hepatitis E virus. Antiviral Res 2019; 163:34-49. [PMID: 30653997 DOI: 10.1016/j.antiviral.2019.01.007] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 01/08/2019] [Accepted: 01/13/2019] [Indexed: 12/26/2022]
Abstract
Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and is the leading cause of enterically-transmitted viral hepatitis worldwide. Increasing numbers of HEV infections, together with no available specific anti-HEV treatment, contributes to the pathogen's major health burden. A robust cell culture system is required for virologic studies and the development of new antiviral drugs. Unfortunately, like other hepatitis viruses, HEV is difficult to propagate in conventional cell lines. Many different cell culture systems have been tested using various HEV strains, but viral replication usually progresses very slowly, and infection with low virion counts results in non-productive HEV replication. However, recent progress involving generation of cDNA clones and passaging primary patient isolates in distinct cell lines has improved in vitro HEV propagation. This review describes various approaches to cultivate HEV in cellular and animal models and how these systems are used to study HEV infections and evaluate anti-HEV drug candidates.
Collapse
Affiliation(s)
- Toni L Meister
- Ruhr-University Bochum, Faculty of Medicine, Department of Molecular and Medical Virology, Bochum, Germany
| | - Janina Bruening
- Ruhr-University Bochum, Faculty of Medicine, Department of Molecular and Medical Virology, Bochum, Germany
| | - Daniel Todt
- Ruhr-University Bochum, Faculty of Medicine, Department of Molecular and Medical Virology, Bochum, Germany.
| | - Eike Steinmann
- Ruhr-University Bochum, Faculty of Medicine, Department of Molecular and Medical Virology, Bochum, Germany.
| |
Collapse
|
|
34
|
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.
Collapse
Affiliation(s)
- Glynn W. Webb
- University of Manchester NHS Foundation Trust, 7 Radnor Rd London NW6 6TT Manchester, UK
| | | |
Collapse
|
|
35
|
Hepatitis E virus: reasons for emergence in humans. Curr Opin Virol 2018; 34:10-17. [PMID: 30497051 DOI: 10.1016/j.coviro.2018.11.006] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 11/08/2018] [Accepted: 11/13/2018] [Indexed: 12/11/2022]
Abstract
Hepatitis E virus (HEV) infects both humans and other animal species. Recently, we have seen a steady increase in autochthonous cases of human HEV infection in certain areas especially in Europe, and large outbreaks in several African countries among the displaced population. This mini-review critically analyzes potential host, environmental, and viral factors that may be associated with the emergence of hepatitis E in humans. The existence of numerous HEV reservoir animals such as pig, deer and rabbit results in human exposure to infected animals via direct contact or through animal meat consumption. Contamination of drinking, irrigation and coastal water by animal and human wastes lead to emergence of endemic cases in industrialized countries and outbreaks in displaced communities especially in war-torn countries.
Collapse
|
|
36
|
Soothill G, Hessey S, Erotocritou M, Griffiths P, Ijaz S, Thorburn D, Ankcorn M, Irish D. Diagnostic utility of hepatitis E virus antigen-specific ELISA versus PCR testing in a cohort of post liver transplant patients in a large university hospital. J Clin Virol 2018; 106:44-48. [PMID: 30053748 DOI: 10.1016/j.jcv.2018.07.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Revised: 07/08/2018] [Accepted: 07/20/2018] [Indexed: 01/28/2023]
|
|
37
|
Choi YH, Zhang X, Tran C, Skinner B. Expression profiles of host immune response-related genes against HEV genotype 3 and genotype 1 infections in rhesus macaques. J Viral Hepat 2018; 25. [PMID: 29532615 PMCID: PMC8996335 DOI: 10.1111/jvh.12890] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Hepatitis E virus (HEV) genotype (gt) 3 infection is food-borne causing sporadic infections in older individuals and gt1 infection is waterborne, often causing epidemics affecting primarily young adults. Although HEV infection causes self-limited disease, gt3 induces chronic infection in immunocompromised individuals. Hepatic host gene expression against gt3 infection remains unknown. Host gene expression profiles for HEV gt1 (n = 3) and gt3 (n = 7) infections were analysed in the livers of experimentally infected rhesus macaques. HEV RNA was detected from 2 to 24 days after inoculation (DAI) in stool and serum, elevated alanine aminotransferase (ALT) activity was detected from 7 to 31 DAI, and anti-HEV antibody became detectable between 12 and 42 DAI. All 10 animals cleared the infection between 34 and 68 DAI. We found that 24%, 48% and 41% of hepatic immune response genes against gt3 infection were upregulated during the early, peak and decline phases of HEV RNA replication. For gt1 infection, 25% of hepatic immune response-related genes were downregulated during early viremia, but 6%, 34% and 37% of genes were upregulated at the early, peak and during decline of HEV RNA replication, respectively. Our study demonstrated distinct differences in the expression profiles of host immune response-related genes of HEV gt3 and gt1 infections in experimentally infected rhesus macaques.
Collapse
Affiliation(s)
- Y. H. Choi
- Laboratory Branch, Division of Viral Hepatitis, NCHHSTP, CDC, Atlanta, GA, USA
| | - X. Zhang
- Laboratory Branch, Division of Viral Hepatitis, NCHHSTP, CDC, Atlanta, GA, USA
| | - C. Tran
- Laboratory Branch, Division of Viral Hepatitis, NCHHSTP, CDC, Atlanta, GA, USA
| | - B. Skinner
- Comparative Medicine Branch, Division of Scientific Resources, NCEZID, CDC, Atlanta, GA, USA
| |
Collapse
|
|
38
|
Gong W, Liu L, Li M, Wang L, Zhang M, Luo Z, Sridhar S, Woo PCY, Wang L. Evaluation of antiviral efficacy of Chinese traditional medicine Babao Dan in rabbits infected with hepatitis E virus. J Gen Virol 2018; 99:1036-1043. [PMID: 29923821 DOI: 10.1099/jgv.0.001089] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Patients with chronic hepatitis B superinfected with HEV may progress to liver failure. Babao Dan (BD) is a traditional Chinese medicine widely used as an auxiliary option for the treatment of chronic hepatitis and liver cancer in China. This study aimed to evaluate the effect of BD on the management of HEV infection in a rabbit model. Sixty-two specific-pathogen-free (SPF) rabbits were divided randomly into five groups and treated with BD or placebo for 2 weeks. All rabbits were inoculated intravenously with rabbit HEV after initial administration. Then, rabbits were administered BD or ribavirin or placebo at 2 weeks post-inoculation (wpi) until faecal virus shedding showed negative. The duration of faecal virus shedding and levels of HEV RNA in faeces were reduced, and anti-HEV antibodies were detected in all rabbits in groups treated with BD before or after inoculation. Ribavirin treatment rapidly cleared HEV infection in SPF rabbits, but anti-HEV antibodies remained negative in 50 % of rabbits treated with ribavirin. These results indicate that ribavirin treatment was more effective in clearing HEV infection, while administration of BD before or after inoculation was effective in clearing HEV infection. Further clinical studies are warranted.
Collapse
Affiliation(s)
- Wanyun Gong
- 1Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China
| | - Lin Liu
- 1Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China
| | - Manyu Li
- 1Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China
| | - Lin Wang
- 1Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China
| | - Mingyu Zhang
- 1Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China
| | - Zhengxin Luo
- 1Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China
| | - Siddharth Sridhar
- 2Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, PR China
| | - Patrick C Y Woo
- 2Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, PR China
| | - Ling Wang
- 1Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China
| |
Collapse
|
|
39
|
Wang M, Huang Y, He M, Peng WJ, Tian DY. Effects of hepatitis E virus infection on interferon production via ISG15. World J Gastroenterol 2018; 24:2173-2180. [PMID: 29853735 PMCID: PMC5974579 DOI: 10.3748/wjg.v24.i20.2173] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Revised: 04/19/2018] [Accepted: 04/23/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the effects of hepatitis E virus (HEV) on the production of type I interferons (IFNs) and determine the underlying mechanisms.
METHODS We measured the production of interferon (IFN)-alpha and -beta (-α/β) in genotype 3 HEV-infected C3A cells at different time points (0, 8, 12, 24, 48, 72 and 120 h) by enzyme-linked immunosorbent assay (ELISA). The expression levels of IFN-stimulated gene (ISG)15 in HEV-infected C3A cells at different time points were tested by western blotting. The plasmid-expressing open reading frame 3 (ORF3) or control plasmids (green fluorescent protein-expressing) were transfected into C3A cells, and the levels of IFN-α/β and ISG15 were evaluated, respectively. Furthermore, the plasmid-expressing ISG15 or small interfering RNA-inhibiting ISG15 was transfected into infected C3A cells. Then, the production of IFN-α/β was also measured by ELISA.
RESULTS We showed that genotype 3 HEV could enhance the production of IFN-α/β and induce elevation of ISG15 in C3A cells. HEV ORF3 protein could enhance the production of IFN-α/β and the expression of ISG15. Additionally, ISG15 silencing enhanced the production of IFN-α/β. Overexpression of ISG15 resulted in the reduction of IFN-α/β.
CONCLUSION HEV may promote production of IFN-α/β and expression of ISG15 via ORF3 in the early stages, and increased ISG15 subsequently inhibited the production of IFN-α/β.
Collapse
Affiliation(s)
- Min Wang
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Ying Huang
- The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510700, Guangdong Province, China
| | - Man He
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Wen-Ju Peng
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - De-Ying Tian
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| |
Collapse
|
|
40
|
Hepatitis E in High-Income Countries: What Do We Know? And What Are the Knowledge Gaps? Viruses 2018; 10:v10060285. [PMID: 29799485 PMCID: PMC6024799 DOI: 10.3390/v10060285] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Revised: 05/16/2018] [Accepted: 05/23/2018] [Indexed: 12/11/2022] Open
Abstract
Hepatitis E virus (HEV) is a positive-strand RNA virus transmitted by the fecal–oral route. HEV genotypes 1 and 2 infect only humans and cause mainly waterborne outbreaks. HEV genotypes 3 and 4 are widely represented in the animal kingdom, and are mainly transmitted as a zoonosis. For the past 20 years, HEV infection has been considered an imported disease in developed countries, but now there is evidence that HEV is an underrecognized pathogen in high-income countries, and that the incidence of confirmed cases has been steadily increasing over the last decade. In this review, we describe current knowledge about the molecular biology of HEV, its clinical features, its main routes of transmission, and possible therapeutic strategies in developed countries.
Collapse
|
|
41
|
Absence of chronic hepatitis E virus infection in liver transplant recipients: Report from a hyperendemic region. Indian J Gastroenterol 2018; 37:160-163. [PMID: 29552742 DOI: 10.1007/s12664-018-0840-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2017] [Accepted: 03/01/2018] [Indexed: 02/04/2023]
Abstract
Most cases of chronic hepatitis E virus (HEV) infection in solid organ transplant recipients are attributable to genotype 3. Although India is hyperendemic for HEV genotype 1, chronic infection in transplant patients has not been reported. In this study, 30 liver transplant recipients were followed up by systematic testing for various markers of HEV (IgM, IgG, HEV-Ag, and RNA) on blood and stool samples obtained pre-transplant, and then at 3 and 6 months post-transplant to look for HEV exposure and persistence. Evidence of HEV infection was found in 6 (20%) cases post-transplant but none of the recipients demonstrated active viremia or antigenemia. This suggests that the circulating genotype of HEV in our population might have limited potential to cause chronic infections.
Collapse
|
|
42
|
Melgaço JG, Gardinali NR, de Mello VDM, Leal M, Lewis-Ximenez LL, Pinto MA. Hepatitis E: Update on Prevention and Control. BIOMED RESEARCH INTERNATIONAL 2018; 2018:5769201. [PMID: 29546064 PMCID: PMC5818934 DOI: 10.1155/2018/5769201] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 11/28/2017] [Accepted: 12/13/2017] [Indexed: 12/20/2022]
Abstract
Hepatitis E virus (HEV) is a common etiology of acute viral hepatitis worldwide. Recombinant HEV vaccines have been developed, but only one is commercially available and licensed in China since 2011. Epidemiological studies have identified genotype 3 as the major cause of chronic infection in immunocompromised individuals. Ribavirin has been shown to be effective as a monotherapy to induce HEV clearance in chronic patients who have undergone solid organ transplant (SOT) under immunosuppressive therapy. Efforts and improvements in prevention and control have been made to reduce the instances of acute and chronic hepatitis E in endemic and nonendemic countries. However, this review shows that further studies are required to demonstrate the importance of preventive vaccination and treatment worldwide, with emphasis on hepatitis E infection in the public health system.
Collapse
Affiliation(s)
- Juliana Gil Melgaço
- Ambulatório/Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Noemi Rovaris Gardinali
- Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Vinicius da Motta de Mello
- Ambulatório/Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Mariana Leal
- Ambulatório/Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Lia Laura Lewis-Ximenez
- Ambulatório/Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Marcelo Alves Pinto
- Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| |
Collapse
|
|
43
|
Guerra JADAA, Kampa KC, Morsoletto DGB, Junior AP, Ivantes CAP. Hepatitis E: A Literature Review. J Clin Transl Hepatol 2017; 5:376-383. [PMID: 29226104 PMCID: PMC5719195 DOI: 10.14218/jcth.2017.00012] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Revised: 06/27/2017] [Accepted: 07/20/2017] [Indexed: 12/13/2022] Open
Abstract
Hepatitis E is the fifth known form of human viral hepatitis. Although not very common in our clinical practice, the incidence in Western countries is increasing. Infection with the hepatitis E virus (HEV) may be related to acute illness, liver failure, chronic hepatitis and cirrhosis. HEV itself is an RNA virus, with eight described genotypes (HEV 1-8), four of which more commonly affect humans and have, thus, been better studied. Besides liver manifestations, genotype 3 is also related to extra-hepatic manifestations, such as neurological, renal and rheumatological. Evolution to chronic disease occurs especially in patients who underwent transplantation, have hematological malignancies requiring chemotherapy, or have infection with the human immunodeficiency virus. The diagnosis may be difficult because of the low availability of tests and due to low sensibility and specificity. The acute form of illness does not have to be treated, but the chronic one does. We present here a literature review of hepatitis E and the relation between chronic hepatitis E and transplantation.
Collapse
Affiliation(s)
- Juliana Ayres de Alencar Arrais Guerra
- Nossa Senhora das Graças Hospital, Alcides Munhoz Street, 433 – Mercês, Curitiba – PR, Brazil
- *Correspondence to: Juliana Ayres de Alencar Arrais Guerra, Nossa Senhora das Graças Hospital, Alcides Munhoz Street, 433 – Mercês, Curitiba – PR 80810-040, Brazil. Tel: +55-41-3240-6060, E-mail:
| | - Katia Cristina Kampa
- Nossa Senhora das Graças Hospital, Alcides Munhoz Street, 433 – Mercês, Curitiba – PR, Brazil
| | | | - Alcindo Pissaia Junior
- Nossa Senhora das Graças Hospital, Alcides Munhoz Street, 433 – Mercês, Curitiba – PR, Brazil
| | | |
Collapse
|
|
44
|
Nan Y, Wu C, Zhao Q, Zhou EM. Zoonotic Hepatitis E Virus: An Ignored Risk for Public Health. Front Microbiol 2017; 8:2396. [PMID: 29255453 PMCID: PMC5723051 DOI: 10.3389/fmicb.2017.02396] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 11/20/2017] [Indexed: 12/27/2022] Open
Abstract
Hepatitis E virus (HEV) is a quasi-enveloped, single-stranded positive-sense RNA virus. HEV belongs to the family Hepeviridae, a family comprised of highly diverse viruses originating from various species. Since confirmation of HEV's zoonosis, HEV-induced hepatitis has been a public health concern both for developing and developed countries. Meanwhile, the demonstration of a broad host range for zoonotic HEV suggests the existence of a variety of transmission routes that could lead to human infection. Moreover, anti-HEV antibody serosurveillance worldwide demonstrates a higher than expected HEV prevalence rate that conflicts with the rarity and sporadic nature of reported acute hepatitis E cases. In recent years, chronic HEV infection, HEV-related acute hepatic failure, and extrahepatic manifestations caused by HEV infection have been frequently reported. These observations suggest a significant underestimation of the number and complexity of transmission routes previously predicted to cause HEV-related disease, with special emphasis on zoonotic HEV as a public health concern. Significant research has revealed details regarding the virology and infectivity of zoonotic HEV in both humans and animals. In this review, the discovery of HEV zoonosis, recent progress in our understanding of the zoonotic HEV host range, and classification of diverse HEV or HEV-like isolates from various hosts are reviewed in a historic context. Ultimately, this review focuses on current understanding of viral pathogenesis and cross-species transmission of zoonotic HEV. Moreover, host factors and viral determinants influencing HEV host tropism are discussed to provide new insights into HEV transmission and prevalence mechanisms.
Collapse
Affiliation(s)
- Yuchen Nan
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Xianyang, China
| | - Chunyan Wu
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Xianyang, China
| | - Qin Zhao
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Xianyang, China
| | - En-Min Zhou
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Xianyang, China
| |
Collapse
|
|
45
|
Risalde MA, Rivero-Juárez A, Romero-Palomo F, Frías M, López-López P, Cano-Terriza D, García-Bocanegra I, Jiménez-Ruíz S, Camacho Á, Machuca I, Gomez-Villamandos JC, Rivero A. Persistence of hepatitis E virus in the liver of non-viremic naturally infected wild boar. PLoS One 2017; 12:e0186858. [PMID: 29117209 PMCID: PMC5678868 DOI: 10.1371/journal.pone.0186858] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2017] [Accepted: 10/09/2017] [Indexed: 12/16/2022] Open
Abstract
Hepatitis E virus (HEV) is an emerging zoonotic pathogen with pigs and wild boar serving as reservoirs for human infection through direct contact with infected animals or the consumption of raw or undercooked pork products. The liver is considered the main target site of HEV replication in swine and an important organ in the pathogenesis of the disease. The aim of this study was to characterize the target liver cells for HEV entry in naturally infected wild boar and to evaluate the type and severity of the pathological changes in order to reach a better understanding of the hepatic pathogenic mechanisms involved in hepatitis E. In total, 58 livers from hunted wild boar were histopathologically evaluated. The presence of specific HEV antibodies in serum was determined by indirect ELISA. Immunohistochemistry was used for the detection of HEV antigen and Real time RT-PCR to detect HEV RNA in liver and serum. HEV seroprevalence in these animals was of 5.197% (CI95%: 1.77–14.14). By Real time RT-PCR, HEV was detected in the liver tissue of four wild boar (6.8%; CI95%: 2.7–16.4) and only one animal was also positive in serum (1.7%; CI95%: 0.3–9.1). The non-viremic animals naturally infected with HEV presented evidence of liver infection, mainly in Kupffer cells and liver sinusoidal endothelial cells, without apparent associated hepatitis lesions. This study supports the hypothesis that low viral titers may persist in the liver of non-viremic individuals, giving thus the possibility of consumption of contaminated liver of animals diagnosed as HEV-negative in serum. Further immunopathogenic studies are necessary to elucidate the mechanisms responsible for this process and to evaluate the protocols of HEV diagnosis in animals destined for human consumption.
Collapse
Affiliation(s)
- María A. Risalde
- Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
| | - Antonio Rivero-Juárez
- Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
| | - Fernando Romero-Palomo
- Dpto. de Anatomía y Anatomía Patológica Veterinaria, Facultad de Veterinaria, Universidad de Córdoba (UCO)—Agrifood Excellence International Campus (ceiA3), Córdoba, Spain
| | - Mario Frías
- Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
| | - Pedro López-López
- Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
| | - David Cano-Terriza
- Dpto. de Sanidad Animal, Facultad de Veterinaria, UCO—ceiA3, Córdoba, Spain
| | | | - Saúl Jiménez-Ruíz
- Dpto. de Sanidad Animal, Facultad de Veterinaria, UCO—ceiA3, Córdoba, Spain
| | - Ángela Camacho
- Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
| | - Isabel Machuca
- Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
| | - José C. Gomez-Villamandos
- Dpto. de Anatomía y Anatomía Patológica Veterinaria, Facultad de Veterinaria, Universidad de Córdoba (UCO)—Agrifood Excellence International Campus (ceiA3), Córdoba, Spain
| | - Antonio Rivero
- Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
- * E-mail:
| |
Collapse
|
|
46
|
Wen GP, Tang ZM, Wang SL, Ji WF, Cai W, Zhang X, Huang SJ, Wu T, Zhang J, Zheng ZZ, Xia NS. Classification of human and zoonotic group hepatitis E virus (HEV) using antigen detection. Appl Microbiol Biotechnol 2017; 101:8585-8594. [PMID: 29038976 DOI: 10.1007/s00253-017-8526-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Revised: 08/24/2017] [Accepted: 09/07/2017] [Indexed: 01/10/2023]
Abstract
Hepatitis E virus (HEV) is one of the major pathogens that cause acute viral hepatitis. The human (genotypes 1 and 2) and zoonotic (genotypes 3 and 4) groups of HEV present different epidemiology and clinical features. In this study, we developed a classification method for rapidly classifying HEV into human or zoonotic groups that combines a general antigen test with a zoonotic group-specific antigen test. Evaluation of serial samples from HEV-infected rhesus monkeys indicated that HEV antigen-positive samples can be classified using the antigen-based classification method. The antigen-based classification method was evaluated further on 55 genotyped samples from acute hepatitis E patients, including 9 human and 46 zoonotic groups. The novel method was completely consistent with the sequencing results: 9/9 for the human groups (100%, 95% confidence interval [CI] 66.4-100%) and 46/46 for the zoonotic groups (100%, 95% CI 92.3-100%). This method was also successfully used for the clustering of some samples that could not be clustered by sequencing. Compared with the sequencing-based method, this method is less time-consuming, less expensive, and less technically complex and is therefore ideal for large numbers of samples. In conclusion, this study provides a convenient and sensitive method for classifying different groups of HEV, and it has potentially important public health applications, especially in underdeveloped areas that cannot afford the high cost of nucleic acid testing.
Collapse
Affiliation(s)
- Gui-Ping Wen
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, XiangAn South Road, Xiamen, 361102, Fujian, People's Republic of China
| | - Zi-Min Tang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, XiangAn South Road, Xiamen, 361102, Fujian, People's Republic of China
| | - Si-Ling Wang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, XiangAn South Road, Xiamen, 361102, Fujian, People's Republic of China
| | - Wen-Fang Ji
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, XiangAn South Road, Xiamen, 361102, Fujian, People's Republic of China.,School of Life Sciences, Xiamen University, XiangAn South Road, Xiamen, 361102, Fujian, People's Republic of China
| | - Wei Cai
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, XiangAn South Road, Xiamen, 361102, Fujian, People's Republic of China.,School of Life Sciences, Xiamen University, XiangAn South Road, Xiamen, 361102, Fujian, People's Republic of China
| | - Xu Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, XiangAn South Road, Xiamen, 361102, Fujian, People's Republic of China
| | - Shou-Jie Huang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, XiangAn South Road, Xiamen, 361102, Fujian, People's Republic of China
| | - Ting Wu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, XiangAn South Road, Xiamen, 361102, Fujian, People's Republic of China
| | - Jun Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, XiangAn South Road, Xiamen, 361102, Fujian, People's Republic of China
| | - Zi-Zheng Zheng
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, XiangAn South Road, Xiamen, 361102, Fujian, People's Republic of China.
| | - Ning-Shao Xia
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, XiangAn South Road, Xiamen, 361102, Fujian, People's Republic of China. .,School of Life Sciences, Xiamen University, XiangAn South Road, Xiamen, 361102, Fujian, People's Republic of China.
| |
Collapse
|
|
47
|
Hepatitis E Virus in Industrialized Countries: The Silent Threat. BIOMED RESEARCH INTERNATIONAL 2016; 2016:9838041. [PMID: 28070522 PMCID: PMC5192302 DOI: 10.1155/2016/9838041] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 11/07/2016] [Accepted: 11/15/2016] [Indexed: 12/11/2022]
Abstract
Hepatitis E virus (HEV) is the main cause of acute viral hepatitis worldwide. Its presence in developing countries has been documented for decades. Developed countries were supposed to be virus-free and initially only imported cases were detected in those areas. However, sporadic and autochthonous cases of HEV infection have been identified and studies reveal that the virus is worldwide spread. Chronic hepatitis and multiple extrahepatic manifestations have also been associated with HEV. We review the data from European countries, where human, animal, and environmental data have been collected since the 90s. In Europe, autochthonous HEV strains were first detected in the late 90s and early 2000s. Since then, serological data have shown that the virus infects quite frequently the European population and that some species, such as pigs, wild boars, and deer, are reservoirs. HEV strains can be isolated from environmental samples and reach the food chain, as shown by the detection of the virus in mussels and in contaminated pork products as sausages or meat. All these data highlight the need of studies directed to control the sources of HEV to protect immunocompromised individuals that seem the weakest link of the HEV epidemiology in industrialized regions.
Collapse
|
|
48
|
van Tong H, Hoan NX, Wang B, Wedemeyer H, Bock CT, Velavan TP. Hepatitis E Virus Mutations: Functional and Clinical Relevance. EBioMedicine 2016; 11:31-42. [PMID: 27528267 PMCID: PMC5049923 DOI: 10.1016/j.ebiom.2016.07.039] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Accepted: 07/29/2016] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) infection is a major cause of acute hepatitis and affects more than 20 million individuals, with three million symptomatic cases and 56,000 recognized HEV-related deaths worldwide. HEV is endemic in developing countries and is gaining importance in developed countries, due to increased number of autochthone cases. Although HEV replication is controlled by the host immune system, viral factors (especially specific viral genotypes and mutants) can modulate HEV replication, infection and pathogenesis. Limited knowledge exists on the contribution of HEV genome variants towards pathogenesis, susceptibility and to therapeutic response. Nonsynonymous substitutions can modulate viral proteins structurally and thus dysregulate virus-host interactions. This review aims to compile knowledge and discuss recent advances on the casual role of HEV heterogeneity and its variants on viral morphogenesis, pathogenesis, clinical outcome and antiviral resistance.
Collapse
Affiliation(s)
- Hoang van Tong
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
| | - Nghiem Xuan Hoan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - Bo Wang
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - C-Thomas Bock
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany.
| | | |
Collapse
|
|
49
|
Pischke S, Iking-Konert C. [Hepatitis E infections in rheumatology. A previously underestimated infectious disease?]. Z Rheumatol 2016; 74:731-6. [PMID: 26450437 DOI: 10.1007/s00393-015-1631-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND The detection and estimation of hepatitis E have greatly changed in recent years. An increasing number of hepatitis E virus (HEV) infections, which were acquired in Europe and knowledge on chronic hepatitis E in immunosuppressed patients, give this infectious disease a new significance in industrial nations in contrast to the previous assumption of merely being a tropical disease with an acute course. Rheumatology patients under immunosuppressive therapy generally have an increased risk of infections. DIAGNOSTICS An HEV infection should always be taken into consideration for the differential diagnostics, particularly in cases of increased transaminase levels and/or diarrhea. In contrast to healthy individuals where the course of HEV infections is mostly innocuous, in immunocompromised patients isolated severe and also chronic courses have been described. Testing of these patients should initially also include PCR of HEV-RNA because serological markers are not always reliable. Therapy with ribavirin (cave: off-label) is a possible therapeutic option and should be considered in individual cases in cooperation with a hepatologist and/or specialist for infections. Whether a general screening for HEV before therapy with biologics is recommendable, cannot yet be conclusively assessed. Additionally, an HEV infection should be included in the differential diagnostics of unclear systemic diseases because the disease can have diverse extrahepatic manifestations. CONCLUSION There are serological indications that hepatitis E can act as a trigger for autoimmune diseases, such as autoimmune hepatitis and cryoglobulinemia but this phenomenon and the underlying pathological mechanisms need further clarification.
Collapse
Affiliation(s)
- S Pischke
- Klinik für Gastroenterologie und Hepatologie, Med. Klinik I, Universitätsklinik Hamburg Eppendorf (UKE), Hamburg, Deutschland
| | - C Iking-Konert
- Klinik für Nephrologie und Rheumatologie, Med. Klinik III, Universitätsklinik Hamburg Eppendorf (UKE), Martinistr. 52, 20246, Hamburg, Deutschland.
| |
Collapse
|
|
50
|
Tavitian S, Peron JM, Huguet F, Kamar N, Abravanel F, Beyne-Rauzy O, Oberic L, Faguer S, Alric L, Roussel M, Gaudin C, Ysebaert L, Huynh A, Recher C. Ribavirin for Chronic Hepatitis Prevention among Patients with Hematologic Malignancies. Emerg Infect Dis 2016. [PMID: 26197210 PMCID: PMC4517705 DOI: 10.3201/eid2108.150199] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Findings among a cohort of 26 patients who had hematologic malignancies and hepatitis E virus (HEV) infection support that HEV can induce chronic hepatitis. However, a 3-month course of ribavirin can induce a rapid viral clearance, reducing the risk for chronic hepatitis and enabling continuation of cytotoxic treatments for underlying malignancies.
Collapse
|