|
1
|
Al Beloushi M, Saleh H, Ahmed B, Konje JC. Congenital and Perinatal Viral Infections: Consequences for the Mother and Fetus. Viruses 2024; 16:1698. [PMID: 39599813 PMCID: PMC11599085 DOI: 10.3390/v16111698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 10/13/2024] [Accepted: 10/26/2024] [Indexed: 11/29/2024] Open
Abstract
Viruses are the most common congenital infections in humans and an important cause of foetal malformations, neonatal morbidity, and mortality. The effects of these infections, which are transmitted in utero (transplacentally), during childbirth or in the puerperium depend on the timing of the infections. These vary from miscarriages (usually with infections in very early pregnancy), congenital malformations (when the infections occur during organogenesis) and morbidity (with infections occurring late in pregnancy, during childbirth or after delivery). The most common of these viruses are cytomegalovirus, hepatitis, herpes simplex type-2, parvovirus B19, rubella, varicella zoster and zika viruses. There are currently very few efficacious antiviral agents licensed for use in pregnancy. For most of these infections, therefore, prevention is mainly by vaccination (where there is a vaccine). The administration of immunoglobulins to those exposed to the virus to offer passive immunity or appropriate measures to avoid being infected would be options to minimise the infections and their consequences. In this review, we discuss some of the congenital and perinatal infections and their consequences on both the mother and fetus and their management focusing mainly on prevention.
Collapse
Affiliation(s)
- Mariam Al Beloushi
- Women’s Wellness and Research Centre Hamad Medical Corporation, Doha P.O. Box 3050, Qatar; (M.A.B.); (H.S.)
- Department of Obstetrics and Gynaecology, Qatar University, Doha P.O. Box 2713, Qatar;
| | - Huda Saleh
- Women’s Wellness and Research Centre Hamad Medical Corporation, Doha P.O. Box 3050, Qatar; (M.A.B.); (H.S.)
- Department of Obstetrics and Gynaecology, Qatar University, Doha P.O. Box 2713, Qatar;
| | - Badreldeen Ahmed
- Department of Obstetrics and Gynaecology, Qatar University, Doha P.O. Box 2713, Qatar;
- Feto Maternal Centre, Al Markhiya Doha, Doha P.O. Box 34181, Qatar
- Department of Obstetrics and Gynaecology Weill Cornell Medicine, Doha P.O. Box 24144, Qatar
| | - Justin C. Konje
- Feto Maternal Centre, Al Markhiya Doha, Doha P.O. Box 34181, Qatar
- Department of Obstetrics and Gynaecology Weill Cornell Medicine, Doha P.O. Box 24144, Qatar
- Department of Health Sciences, University of Leicester, P.O. Box 7717, Leicester LE2 7LX, UK
| |
Collapse
|
|
2
|
Shrestha A, Basnet S, Kc S. Subclinical hepatitis E virus genotype 1 infection: The concept of "dynamic human reservoir". World J Hepatol 2024; 16:506-510. [PMID: 38689746 PMCID: PMC11056895 DOI: 10.4254/wjh.v16.i4.506] [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: 12/28/2023] [Revised: 02/22/2024] [Accepted: 03/28/2024] [Indexed: 04/24/2024] Open
Abstract
Hepatitis E virus (HEV) is hyperendemic in South Asia and Africa accounting for half of total Global HEV burden. There are eight genotypes of HEV. Among them, the four common ones known to infect humans, genotypes 1 and 2 are prevalent in the developing world and genotypes 3 and 4 are causing challenge in the industrialized world. Asymptomatic HEV viremia in the general population, especially among blood donors, has been reported in the literature worldwide. The clinical implications related to this asymptomatic viremia are unclear and need further exploration. Detection of viremia due to HEV genotype 1 infection, apparently among healthy blood donors is also reported without much knowledge about its infection rate. Similarly, while HEV genotype 3 is known to be transmitted via blood transfusion in humans and has been subjected to screening in many European nations, instances of transmission have also been documented albeit without significant clinical consequences. Epidemiology of HEV genotype 1 in endemic areas often show waxing and waning pattern. Occasional sporadic occurrence of HEV infection interrupted by outbreaks have been frequently seen. In absence of known animal reservoir, where HEV exists in between outbreak is a mystery that needs further exploration. However, occurrence of asymptomatic HEV viremia due to HEV genotype 1 during epidemiologically quiescent period may explain that this phenomenon may act as a dynamic reservoir. Since HEV genotype 1 infection cannot cause chronicity, subclinical transient infection and transmission of virus might be the reason it sustains in interepidemic period. This might be the similar phenomenon with SARS COVID-19 corona virus infection which is circulating worldwide in distinct phases with peaks and plateaus despite vaccination against it. In view of existing evidence, we propose the concept of "Dynamic Human Reservoir." Quiescent subclinical infection of HEV without any clinical consequences and subsequent transmission may contribute to the existence of the virus in a community. The potential for transmitting HEV infection by asymptomatic HEV infected individuals by fecal shedding of virus has not been reported in literature. This missing link may be a key to Pandora's box in understanding epidemiology of HEV infection in genotype 1 predominant region.
Collapse
Affiliation(s)
- Ananta Shrestha
- Department of Hepatology, Alka Hospital, Kathmandu 44600, Nepal
| | - Suresh Basnet
- Department of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, United States
| | - Sudhamshu Kc
- Department of Hepatology, National Academy of Medical Sciences, Kathmandu 44600, Nepal.
| |
Collapse
|
|
3
|
Viral agents (2nd section). Transfusion 2024; 64 Suppl 1:S19-S207. [PMID: 38394038 DOI: 10.1111/trf.17630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Accepted: 12/02/2023] [Indexed: 02/25/2024]
|
|
4
|
Williamson C, Nana M, Poon L, Kupcinskas L, Painter R, Taliani G, Heneghan M, Marschall HU, Beuers U. EASL Clinical Practice Guidelines on the management of liver diseases in pregnancy. J Hepatol 2023; 79:768-828. [PMID: 37394016 DOI: 10.1016/j.jhep.2023.03.006] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 03/10/2023] [Indexed: 07/04/2023]
Abstract
Liver diseases in pregnancy comprise both gestational liver disorders and acute and chronic hepatic disorders occurring coincidentally in pregnancy. Whether related to pregnancy or pre-existing, liver diseases in pregnancy are associated with a significant risk of maternal and fetal morbidity and mortality. Thus, the European Association for the Study of Liver Disease invited a panel of experts to develop clinical practice guidelines aimed at providing recommendations, based on the best available evidence, for the management of liver disease in pregnancy for hepatologists, gastroenterologists, obstetric physicians, general physicians, obstetricians, specialists in training and other healthcare professionals who provide care for this patient population.
Collapse
|
|
5
|
Khuroo MS. Discovery of Hepatitis E and Its Impact on Global Health: A Journey of 44 Years about an Incredible Human-Interest Story. Viruses 2023; 15:1745. [PMID: 37632090 PMCID: PMC10459142 DOI: 10.3390/v15081745] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 08/09/2023] [Accepted: 08/10/2023] [Indexed: 08/27/2023] Open
Abstract
The story of the discovery of hepatitis E originated in the late 1970s with my extreme belief that there was a hidden saga in the relationship between jaundice and pregnancy in developing countries and the opportunity for a massive epidemic of viral hepatitis, which hit the Gulmarg Kashmir region in November 1978. Based on data collected from a door-to-door survey, the existence of a new disease, epidemic non-A, non-B hepatitis, caused by a hitherto unknown hepatitis virus, was announced. This news was received by the world community with hype and skepticism. In the early 1980s, the world watched in awe as an extreme example of human self-experimentation led to the identification of VLP. In 1990, a cDNA clone from the virus responsible for epidemic non-A, non-B hepatitis was isolated. Over the years, we traversed three eras of ambiguity, hope, and hype of hepatitis E research and conducted several seminal studies to understand the biology of HEV and manifestations of hepatitis E. Many milestones have been reached on the long and winding road of hepatitis E research to understand the structure, biology, and diversity of the agent, changing the behavior of the pathogen in developed countries, and the discovery of a highly effective vaccine.
Collapse
Affiliation(s)
- Mohammad Sultan Khuroo
- Digestive Diseases Centre, Dr. Khuroo's Medical Clinic, Srinagar, Jammu & Kashmir 190010, India
| |
Collapse
|
|
6
|
Cardoso M, Ragan I, Hartson L, Goodrich RP. Emerging Pathogen Threats in Transfusion Medicine: Improving Safety and Confidence with Pathogen Reduction Technologies. Pathogens 2023; 12:911. [PMID: 37513758 PMCID: PMC10383627 DOI: 10.3390/pathogens12070911] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 06/30/2023] [Accepted: 07/02/2023] [Indexed: 07/30/2023] Open
Abstract
Emerging infectious disease threats are becoming more frequent due to various social, political, and geographical pressures, including increased human-animal contact, global trade, transportation, and changing climate conditions. Since blood products for transfusion are derived from donated blood from the general population, emerging agents spread by blood contact or the transfusion of blood products are also a potential risk. Blood transfusions are essential in treating patients with anemia, blood loss, and other medical conditions. However, these lifesaving procedures can contribute to infectious disease transmission, particularly to vulnerable populations. New methods have been implemented on a global basis for the prevention of transfusion transmissions via plasma, platelets, and whole blood products. Implementing proactive pathogen reduction methods may reduce the likelihood of disease transmission via blood transfusions, even for newly emerging agents whose transmissibility and susceptibility are still being evaluated as they emerge. In this review, we consider the Mirasol PRT system for blood safety, which is based on a photochemical method involving riboflavin and UV light. We provide examples of how emerging threats, such as Ebola, SARS-CoV-2, hepatitis E, mpox and other agents, have been evaluated in real time regarding effectiveness of this method in reducing the likelihood of disease transmission via transfusions.
Collapse
Affiliation(s)
- Marcia Cardoso
- Terumo BCT, Inc., TERUMO Böood and Cell Technologies, Zaventem, 41 1930 Brussels, Belgium
| | - Izabela Ragan
- Infectious Disease Research Center, Department of Biomedical Science, Colorado State University, Fort Collins, CO 80521, USA
| | - Lindsay Hartson
- Infectious Disease Research Center, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80521, USA
| | - Raymond P Goodrich
- Infectious Disease Research Center, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80521, USA
| |
Collapse
|
|
7
|
Higher Risk of HEV Transmission and Exposure among Blood Donors in Europe and Asia in Comparison to North America: A Meta-Analysis. Pathogens 2023; 12:pathogens12030425. [PMID: 36986347 PMCID: PMC10059948 DOI: 10.3390/pathogens12030425] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/01/2023] [Accepted: 03/05/2023] [Indexed: 03/10/2023] Open
Abstract
Background and aims: The increasing number of diagnosed hepatitis E virus (HEV) infections in Europe has led to the implementation of the testing of blood products in various countries. Many nations have not yet implemented such screening. To assess the need for HEV screening in blood products worldwide, we conducted a systematic review and meta-analysis assessing HEV RNA positivity and anti-HEV seroprevalence in blood donors. Methods: Studies reporting anti-HEV IgG/IgM or HEV RNA positivity rates among blood donors worldwide were identified via predefined search terms in PubMed and Scopus. Estimates were calculated by pooling study data with multivariable linear mixed-effects metaregression analysis. Results: A total of 157 (14%) of 1144 studies were included in the final analysis. The estimated HEV PCR positivity rate ranged from 0.01 to 0.14% worldwide, with strikingly higher rates in Asia (0.14%) and Europe (0.10%) in comparison to North America (0.01%). In line with this, anti-HEV IgG seroprevalence in North America (13%) was lower than that in Europe (19%). Conclusions: Our data demonstrate large regional differences regarding the risk of HEV exposure and blood-borne HEV transmission. Considering the cost–benefit ratio, this supports blood product screening in high endemic areas, such as Europe and Asia, in contrast to low endemic regions, such as the U.S.
Collapse
|
|
8
|
Geng Y, Shi T, Wang Y. Transmission of Hepatitis E Virus. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:73-92. [PMID: 37223860 DOI: 10.1007/978-981-99-1304-6_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Transmission of hepatitis E virus (HEV) occurs predominantly by the fecal-oral route. Large epidemics of hepatitis E in the developing countries of Asia and Africa are waterborne and spread through contaminated drinking water. The reservoir of HEV in developed countries is believed to be in animals with zoonotic transmission to humans, possibly through direct contact or the consumption of undercooked contaminated meat. And HEV transmission through blood transfusion, organ transplantation, and vertical transmission has been reported.
Collapse
Affiliation(s)
- Yansheng Geng
- Key Laboratory of Public Health Safety of Hebei Province, School of Public Health, Hebei University, Baoding, China
| | - Tengfei Shi
- Key Laboratory of Public Health Safety of Hebei Province, School of Public Health, Hebei University, Baoding, China
| | - Youchun Wang
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, China.
| |
Collapse
|
|
9
|
Aziz AB, Øverbø J, Dudman S, Julin CH, Kwon YJG, Jahan Y, Ali M, Dembinski JL. Hepatitis E Virus (HEV) Synopsis: General Aspects and Focus on Bangladesh. Viruses 2022; 15:63. [PMID: 36680103 PMCID: PMC9866510 DOI: 10.3390/v15010063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 12/15/2022] [Accepted: 12/21/2022] [Indexed: 12/28/2022] Open
Abstract
HEV is the most common cause of acute hepatitis globally. This review summarizes the latest knowledge on the epidemiology, clinical characteristics, testing, and treatment of HEV infection. We also focused on Bangladesh to highlight the distinct challenges and the possible remedies. In low-income settings, the virus is mainly transmitted between people by fecal contamination of drinking water causing large outbreaks, and sporadic cases. The disease is usually mild and self-limiting acute hepatitis. Still, pregnant women and their offspring in low-income countries are at particular risk for severe disease, with up to 20% maternal mortality. Despite the high burden of the disease, HEV remains a relatively neglected virus, with detection hampered by costly tests and a lack of suitable treatments. Molecular PCR diagnostics, together with ELISA antibody tests, remain the preferred methods for diagnosis of HEV; however, rapid bedside diagnostics are available and could offer a practical alternative, especially in low-income countries. One vaccine (HEV 239) is only available in China and Pakistan, as efficacy against the other genotypes remains uncertain. The effectiveness trial conducted in Bangladesh might lead the way in gathering more efficacy data and could, together with improved surveillance and raised awareness, dramatically reduce the global burden of HEV.
Collapse
Affiliation(s)
- Asma Binte Aziz
- Institute of Clinical Medicine, University of Oslo, 0315 Oslo, Norway
- International Vaccine Institute (IVI), Seoul 08800, Republic of Korea
| | - Joakim Øverbø
- Institute of Clinical Medicine, University of Oslo, 0315 Oslo, Norway
- Norwegian Institute of Public Health (NIPH), Division of Infection Control and Environmental Health, 0213 Oslo, Norway
| | - Susanne Dudman
- Institute of Clinical Medicine, University of Oslo, 0315 Oslo, Norway
| | - Cathinka Halle Julin
- Norwegian Institute of Public Health (NIPH), Division of Infection Control and Environmental Health, 0213 Oslo, Norway
| | | | - Yasmin Jahan
- Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-0046, Japan
| | - Mohammad Ali
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, MD 21205, USA
| | - Jennifer L. Dembinski
- Norwegian Institute of Public Health (NIPH), Division of Infection Control and Environmental Health, 0213 Oslo, Norway
| |
Collapse
|
|
10
|
Shata MTM, Hetta HF, Sharma Y, Sherman KE. Viral hepatitis in pregnancy. J Viral Hepat 2022; 29:844-861. [PMID: 35748741 PMCID: PMC9541692 DOI: 10.1111/jvh.13725] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 12/17/2021] [Accepted: 06/13/2022] [Indexed: 12/09/2022]
Abstract
Viral hepatitis is caused by a heterogenous group of viral agents representing a wide range of phylogenetic groups. Many viruses can involve the liver and cause liver injury but only a subset are delineated as 'hepatitis viruses' based upon their primary site of replication and tropism for hepatocytes which make up the bulk of the liver cell population. Since their discovery, beginning with the agent that caused serum hepatitis in the 1960s, the alphabetic designations have been utilized. To date, we have five hepatitis viruses, A through E, though it is postulated that others may exist. This chapter will focus on those viruses. Note that hepatitis D is included as a subset of hepatitis B, as it cannot exist without concurrent hepatitis B infection. Pregnancy has the potential to affect all aspects of these viral agents due to the unique immunologic and physiologic changes that occur during and after the gestational period. In this review, we will discuss the most common viral hepatitis and their effects during pregnancy.
Collapse
Affiliation(s)
- Mohamed Tarek M. Shata
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA
| | - Helal F. Hetta
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA,Department of Medical Microbiology and Immunology, Faculty of MedicineAssiut UniversityAssiutEgypt
| | - Yeshika Sharma
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA
| | - Kenneth E. Sherman
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA
| |
Collapse
|
|
11
|
Wu S, Yi W, Gao Y, Deng W, Bi X, Lin Y, Yang L, Lu Y, Liu R, Chang M, Shen G, Hu L, Zhang L, Li M, Xie Y. Immune Mechanisms Underlying Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B Patients With Viral Coinfection. Front Immunol 2022; 13:893512. [PMID: 35634301 PMCID: PMC9130599 DOI: 10.3389/fimmu.2022.893512] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 04/11/2022] [Indexed: 12/28/2022] Open
Abstract
It is considered that chronic hepatitis B patients have obtained functional cure if they get hepatitis B surface antigen (HBsAg) seroclearance after treatment. Serum HBsAg is produced by cccDNA that is extremely difficult to clear and dslDNA that is integrated with host chromosome. High HBsAg serum level leads to failure of host immune system, which makes it unable to produce effective antiviral response required for HBsAg seroclerance. Therefore, it is very difficult to achieve functional cure, and fewer than 1% of chronic hepatitis B patients are cured with antiviral treatment annually. Some chronic hepatitis B patients are coinfected with other chronic viral infections, such as HIV, HCV and HDV, which makes more difficult to cure. However, it is found that the probability of obtaining HBsAg seroclearance in patients with coinfection is higher than that in patients with HBV monoinfection, especially in patients with HBV/HIV coinfection who have an up to 36% of HBsAg 5-year-seroclerance rate. The mechanism of this interesting phenomenon is related to the functional reconstruction of immune system after antiretroviral therapy (ART). The quantity increase and function recovery of HBV specific T cells and B cells, and the higher level of cytokines and chemokines such as IP-10, GM-CSF, promote HBsAg seroclearance. This review summarizes recent studies on the immune factors that have influence on HBsAg seroconversion in the chronic hepatitis B patients with viral coinfection, which might provide new insights for the development of therapeutic approaches to partially restore the specific immune response to HBV and other viruses.
Collapse
Affiliation(s)
- Shuling Wu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wei Yi
- Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuanjiao Gao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wen Deng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoyue Bi
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yanjie Lin
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Liu Yang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ruyu Liu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Min Chang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ge Shen
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Leiping Hu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| |
Collapse
|
|
12
|
Caballeria L, Martínez-Escudé A, Expósito C, Rodríguez L, Torán-Monserrat P. Hepatitis E. Epidemiología y relevancia clínica. FMC - FORMACIÓN MÉDICA CONTINUADA EN ATENCIÓN PRIMARIA 2022; 29:230-238. [DOI: 10.1016/j.fmc.2021.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
|
|
13
|
Damiris K, Aghaie Meybodi M, Niazi M, Pyrsopoulos N. Hepatitis E in immunocompromised individuals. World J Hepatol 2022; 14:482-494. [PMID: 35582299 PMCID: PMC9055194 DOI: 10.4254/wjh.v14.i3.482] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/15/2021] [Accepted: 02/13/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) originally identified as a cause of acute icteric hepatitis in developing countries has grown to be a cause of zoonotic viral hepatitis in developed countries such as the United States. While there are eight identified genotypes to date, genotype 1 (HEV1), HEV2, HEV3, HEV4 are the most common to infect humans. HEV1 and HEV2 are most common in developing countries including Latina America, Africa and Asia, and are commonly transmitted through contaminated water supplies leading to regional outbreaks. In contrast HEV3 and HEV4 circulate freely in many mammalian animals and can lead to occasional transmission to humans through fecal contamination or consumption of undercooked meat. The incidence and prevalence of HEV in the United States is undetermined given the absence of FDA approved serological assays and the lack of commercially available testing. In majority of cases, HEV infection is a self-limiting hepatitis requiring only symptomatic treatment. However, this is not the case in immunocompromised individuals, including those that have undergone solid organ or stem cell transplantation. In this subset of patients, chronic infection can be life threatening as hepatic insult can lead to inflammation and fibrosis with subsequent cirrhosis and death. The need for re-transplantation as a result of post-transplant hepatitis is of great concern. In addition, there have been many reported incidents of extrahepatic manifestations, for which the exact mechanisms remain to be elucidated. The cornerstone of treatment in immunocompromised solid organ transplant recipients is reduction of immunosuppressive therapies, while attempting to minimize the risk of organ rejection. Subsequent treatment options include ribavirin, and pegylated interferon alpha in those who have demonstrated ribavirin resistance. Further investigation assessing safety and efficacy of anti-viral therapy is imperative given the rising global health burden. Given this concern, vaccination has been approved in China with other investigations underway throughout the world. In this review we introduce the epidemiology, diagnosis, clinical manifestations, and treatment of HEV, with emphasis on immunocompromised individuals in the United States.
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
|
|
14
|
Aggarwal R, Goel A. Hepatitis E: Current Status in India. Clin Liver Dis (Hoboken) 2021; 18:168-172. [PMID: 34691406 PMCID: PMC8518337 DOI: 10.1002/cld.1146] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 05/30/2021] [Accepted: 06/04/2021] [Indexed: 02/04/2023] Open
Affiliation(s)
- Rakesh Aggarwal
- Jawaharlal Institute of Postgraduate Medical Education and ResearchPuducherryIndia
| | - Amit Goel
- Department of GastroenterologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
| |
Collapse
|
|
15
|
Al Dossary RA, Alnafie AN, Aljaroodi SA, Rahman JU, Hunasemarada BC, Alkharsah KR. Prevalence of Hepatitis E Virus Infection Among Blood Donors in the Eastern Province of Saudi Arabia. J Multidiscip Healthc 2021; 14:2381-2390. [PMID: 34475765 PMCID: PMC8407670 DOI: 10.2147/jmdh.s328029] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 08/16/2021] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Hepatitis E virus (HEV) causes acute hepatitis in humans and constitutes a major problem for immunocompromised patients, patients with hematological diseases, and pregnant women. It is transmitted mainly through fecal oral route; however, transmission through blood and blood products is reported globally and becoming a health concern. We sought to determine the prevalence of HEV among blood donors in the Eastern Province of Saudi Arabia using molecular as well as serological assays to assess the safety of blood transfusion and the need for HEV screening among blood donors. PATIENTS AND METHODS A total of 806 whole blood samples were collected from blood donors between May and November 2020 and tested for anti-HEV IgG and IgM antibodies by ELISA and for HEV RNA by RT-PCR. RESULTS The overall seroprevalence of HEV IgG antibodies was 3.2% with no statistically significant difference between the non-Saudis (3.28%) and Saudis (3.17%) (p value 0.929) or between males (3.14%) and females (4.88%) (p value 0.527). None of the IgG positive individuals had IgM antibodies. HEV RNA was not detected in any of the blood donors. CONCLUSION HEV seroprevalence is low among blood donors in the Eastern Province of Saudi Arabia and may constitute minimal risk for transfusion associated infections.
Collapse
Affiliation(s)
- Reem A Al Dossary
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| | - Awatif N Alnafie
- Department of Pathology, College of Medicine, King Fahad Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Salma Ali Aljaroodi
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| | - Jawad Ur Rahman
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| | - Basavaraj C Hunasemarada
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| | - Khaled R Alkharsah
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia
| |
Collapse
|
|
16
|
Koyuncu A, Mapemba D, Ciglenecki I, Gurley ES, Azman AS. Setting a Course for Preventing Hepatitis E in Low and Lower-Middle-Income Countries: A Systematic Review of Burden and Risk Factors. Open Forum Infect Dis 2021; 8:ofab178. [PMID: 34113684 PMCID: PMC8186248 DOI: 10.1093/ofid/ofab178] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 04/09/2021] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) is responsible for outbreaks of acute jaundice in Africa and Asia, many of which occur among displaced people or in crisis settings. Although an efficacious vaccine for HEV has been developed, we lack key epidemiologic data needed to understand how best to use the vaccine for hepatitis E control in endemic countries. METHODS We conducted a systematic review of articles published on hepatitis E in low-income and lower-middle-income countries in Africa and Asia. We searched PubMed, Scopus, and Embase databases to identify articles with data on anti-HEV immunoglobulin (Ig)G seroprevalence, outbreaks of HEV, or risk factors for HEV infection, disease, or death, and all relevant data were extracted. Using these data we describe the evidence around temporal and geographical distribution of HEV transmission and burden. We estimated pooled age-specific seroprevalence and assessed the consistency in risk factor estimates. RESULTS We extracted data from 148 studies. Studies assessing anti-HEV IgG antibodies used 18 different commercial assays. Most cases of hepatitis E during outbreaks were not confirmed. Risk factor data suggested an increased likelihood of current or recent HEV infection and disease associated with fecal-oral transmission of HEV, as well as exposures to blood and animals. CONCLUSIONS Heterogeneity in diagnostic assays used and exposure and outcome assessment methods hinder public health efforts to quantify burden of disease and evaluate interventions over time and space. Prevention tools such as vaccines are available, but they require a unified global strategy for hepatitis E control to justify widespread use.
Collapse
Affiliation(s)
| | - Daniel Mapemba
- South African Field Epidemiology Training Program, National Institute for Communicable Diseases, Division of National Health Laboratory Services, Johannesburg, South Africa
| | | | - Emily S Gurley
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Andrew S Azman
- Médecins Sans Frontières, Geneva, Switzerland
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| |
Collapse
|
|
17
|
Mishra KK, Patel K, Trivedi A, Patel P, Ghosh K, Bharadva S. Risk of hepatitis-E virus infections among blood donors in a regional blood transfusion centre in western India. Transfus Med 2021; 31:193-199. [PMID: 33738857 DOI: 10.1111/tme.12760] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 01/02/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Hepatitis-E virus (HEV) is an emerging infectious threat to blood safety. The enormity of the transmission of HEV and its clinical consequence are issues currently under debate. This study aimed to evaluate the prevalence of HEV-RNA in blood donors in western India. MATERIALS AND METHODS We screened 13 050 blood donors for HEV using HEV-RNA screening of 10 mini-pools using RealStar HEV RT-PCR Kit (95% limit of detection (LOD): 4.7 IU/ml). Furthermore, all HEV-RNA-positive donors were investigated for the presence of IgM/IgG antibody along with liver function tests. RESULTS Of the 13 050 blood donations, 7 (0.53%) were found to be HEV-RNA positive, and the prevalence of HEV nucleic acid testing yield cases among blood donors was 1 in 1864. All seven HEV-RNA-positive samples were tested with anti-HEV IgM and anti-HEV IgG antibodies; this resulted in two (28.5%) positive anti-HEV IgM and two (28.5%) positive anti-HEV IgG antibodies. Hepatic activity was measured, with two of seven HEV-RNA-positive donors demonstrating abnormal serum glutamic oxaloacetic transaminase (SGOT) andserum glutamic pyruvic transaminase (SGPT). Two HEV-RNA-positive blood donors who had abnormal SGOT and SGPT were found to have a high HEV viral load. Furthermore, we were able to follow up two HEV-RNA donors, and both were HEV-RNA positive and had anti-HEV IgM and anti-HEV IgG antibodies; moreover, their liver function tests were also abnormal. One of the HEV-RNA donors with high viral load did show hepatitis-E-like virus on electron microscopy. CONCLUSION Our studies indicate that there is a significant risk of blood-borne transmission of HEV. This finding may help to provide a direction towards the safety of blood transfusions in clinical settings in countries like India, which fall under the endemic category for HEV infection.
Collapse
Affiliation(s)
- Kanchan K Mishra
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
| | - Krima Patel
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
| | - Apeksha Trivedi
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
| | - Parizad Patel
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
| | - Kanjaksha Ghosh
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
| | - Sumit Bharadva
- Department of Transfusion Medicine, Surat Raktadan Kendra and Research Centre, Surat, India
| |
Collapse
|
|
18
|
Dynamics of Hepatitis E Virus (HEV) Antibodies and Development of a Multifactorial Model To Improve the Diagnosis of HEV Infection in Resource-Limited Settings. J Clin Microbiol 2021; 59:JCM.02321-20. [PMID: 33239375 DOI: 10.1128/jcm.02321-20] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 11/19/2020] [Indexed: 02/06/2023] Open
Abstract
Serological markers are important for the diagnosis of hepatitis E virus (HEV) infection. This study aims to compare the diagnostic performance of the anti-HEV IgM and the HEV antigen (Ag) assays and establish a multifactorial model to improve the diagnosis of current HEV infection when HEV RNA detection is not available. A total of 809 serum samples, including 325 anti-HEV IgM-positive and 484 anti-HEV IgM-negative samples, were tested for HEV RNA. The anti-HEV IgM assay had very high sensitivity (99.4%) but moderate accuracy (79.2%) and specificity (74.3%). By retrospective follow-up of 58 patients with sequential samples (n = 143) tested for anti-HEV antibodies, we found anti-HEV IgM remained positive for more than 10 months in some HEV-infected patients, when HEV RNA was already undetectable; thus, decision solely based on anti-HEV IgM may lead to misdiagnosis. In contrast, the HEV Ag assay had very high specificity (100%). However, the detection efficiency of HEV Ag greatly diminished when the HEV RNA level was low or the anti-HEV IgG level was high. By logistic regression, a model integrating anti-HEV IgM, alanine aminotransferase, and HEV Ag was proposed, and the cutoff value was determined based on the testing results of the 143 sequential samples. The model was further evaluated with 67 randomly selected IgM-positive samples from single-visit patients. Overall, the model outperformed the anti-HEV IgM or the HEV Ag assay in the diagnosis of current HEV infection (sensitivity/specificity/accuracy, 89.5%/95.2%/91.9%). The area under the receiver operating characteristics curve of the model was greater than 0.97.
Collapse
|
|
19
|
Lu J, Li Q, Jiang J, Li Z, Wang P, Sheng Z, Lai R, Zhou H, Cai W, Wang H, Guo Q, Gui H, Xie Q. Laboratory-based Surveillance and Clinical Profile of Sporadic HEV Infection in Shanghai, China. Virol Sin 2021; 36:644-654. [PMID: 33433848 DOI: 10.1007/s12250-020-00336-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 10/30/2020] [Indexed: 12/17/2022] Open
Abstract
The study aimed to describe the epidemiological, virological and clinical features of sporadic HEV infection in eastern China. A total of 6112 patient sera were tested for anti-HEV IgG or anti-HEV IgM during one consecutive year (between August 2018 and July 2019). HEV RNA presence was evaluated by RT-PCR and HEV sequences were phylogenetically analyzed. Clinical features of confirmed HEV-infected patients were delineated. The sero-positivity rate of anti-HEV IgG maintained stable around 40%, while an obvious winter spike of anti-HEV IgM prevalence was observed. A total of 111 patients were confirmed of HEV viremia by molecular diagnosis. Subtype 4d was predominant. Phylogenetic analyses suggest that certain strains circulate across species and around the country. Subjects with confirmed current HEV infection had a high median age (58 years) and males were predominant (62.2%). Most patients presented with jaundice (75.7%) and anorexia (68.0%). Significantly elevated levels of liver enzymes and bilirubin were observed. Remarkably, the baseline bilirubin level was positively correlated with illness severity. Pre-existing HBV carriage may deteriorate illness. The clinical burden caused by locally acquired HEV infection is increasing. Surveillance should be enforced especially during the transition period from winter to spring. Patients with higher level of bilirubin at disease onset had slower recovery from HEV infection.
Collapse
Affiliation(s)
- Jie Lu
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Qing Li
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Jiayuan Jiang
- Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Ziqiang Li
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Peiyun Wang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zike Sheng
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Rongtao Lai
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Huijuan Zhou
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Wei Cai
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Hui Wang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Qing Guo
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
| | - Honglian Gui
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
| |
Collapse
|
|
20
|
Dahl V, Majeed A, Wikman A, Norda R, Edgren G. Transmission of viral hepatitis through blood transfusion in Sweden, 1968 to 2012. ACTA ACUST UNITED AC 2020; 25. [PMID: 32720634 PMCID: PMC7384284 DOI: 10.2807/1560-7917.es.2020.25.29.1900537] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Introduction Viral hepatitis remains a significant threat to transfusion safety, although largely mitigated by donor screening. Aim Our objective was to estimate the past and present burden of transfusion transmission of all types of viral hepatitis (A to E) and to find undiagnosed infections with hepatitis C virus (HCV). Method We performed a retrospective cohort study using a database of the entire computerised transfusion experience of Sweden from 1968 to 2012 and linking it to a nationwide database of notifiable infections. We then used two independent statistical approaches. Firstly, we tracked recipients of blood from donors with confirmed viral hepatitis. Secondly, we computed a donor-specific risk score, defined as the difference between the observed and the expected number of HCV infections among all previous recipients of all donors, where thresholds were determined using simulation. Results Among 1,146,307 transfused patients, more than 5,000 were infected with HCV. Transfusion transmission only occurred before 1992 when donor screening had been completely implemented. Overall, we found 44 donors and 1,180 recipients likely to be infected with HCV who were still alive but who remained undiagnosed. Conclusion There is still a substantial number of individuals in Sweden who have probably been infected with HCV through blood transfusion and who are still unaware of their infection. We recommend that a follow-up study should be conducted to validate the method we used by approaching these individuals and offer testing. This would also serve as an opportunity to offer treatment to those who remain infected.
Collapse
Affiliation(s)
- Viktor Dahl
- Department of Public Health Analysis and Data Management, Public Health Agency of Sweden, Stockholm, Sweden
| | - Ammar Majeed
- Central Clinical School, Monash University, Melbourne, Australia.,Department of Gastroenterology, Alfred Health, Melbourne, Australia.,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Agneta Wikman
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.,Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Rut Norda
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
| | - Gustaf Edgren
- Department of Cardiology, Södersjukhuset, Stockholm, Sweden.,Department of Medicine Solna, Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden
| |
Collapse
|
|
21
|
Webb GW, Kelly S, Dalton HR. Hepatitis A and Hepatitis E: Clinical and Epidemiological Features, Diagnosis, Treatment, and Prevention. CLINICAL MICROBIOLOGY NEWSLETTER 2020; 42:171-179. [PMID: 33110280 PMCID: PMC7581387 DOI: 10.1016/j.clinmicnews.2020.10.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Hepatitis A and E are both ancient diseases but have only been properly recognized as being caused by distinct pathogens in modern times. Despite significantly different genomic structures, both viruses employ remarkably similar strategies to avoid host detection and increase environmental transmission. There are millions of cases of acute viral hepatitis due to hepatitis A virus (HAV) and hepatitis E virus (HEV) each year, resulting in tens of thousands of deaths. The presentations can be clinically indistinguishable, but each virus also has a range of less common but more specific phenotypes. The epidemiology of HAV is complex, and is shifting in countries that are making improvements to public health and sanitation. HEV presents a significant public health challenge in resource-limited settings but has historically been incorrectly regarded as having little clinical relevance in industrialized countries.
Collapse
Affiliation(s)
- Glynn W Webb
- Royal Liverpool University Hospital, Liverpool, United Kingdom
- University of Liverpool, Liverpool, United Kingdom
- University of Manchester, Manchester, United Kingdom
| | - Sophie Kelly
- Royal Liverpool University Hospital, Liverpool, United Kingdom
- University of Liverpool, Liverpool, United Kingdom
| | - Harry R Dalton
- University of Manchester, Manchester, United Kingdom
- Retired Consultant, Department of Gastroenterology, Royal Cornwall Hospital, Truro, Cornwall, United Kingdom
| |
Collapse
|
|
22
|
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: 105] [Impact Index Per Article: 21.0] [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
|
|
23
|
Nasir M, Wu GY. HEV and HBV Dual Infection: A Review. J Clin Transl Hepatol 2020; 8:313-321. [PMID: 33083255 PMCID: PMC7562801 DOI: 10.14218/jcth.2020.00030] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 05/29/2020] [Accepted: 06/07/2020] [Indexed: 12/17/2022] Open
Abstract
Hepatitis E virus (HEV) is a global health problem, affecting about 20 million people worldwide. There is significant overlap of hepatitis B virus (HBV) and HEV endemicity in many Asian countries where dual infections with HEV and HBV can occur. Though the clinical course of HEV is largely self-limited, HEV superinfection in patients with chronic hepatitis B (CHB) can result in acute exacerbation of underlying CHB. HEV superinfection in patients with CHB-related cirrhosis has been identified as a risk factor for decompensated cirrhosis and an independent predictor of mortality. Whereas acute HEV infection in pregnancy can cause fulminant liver failure, the few studies on pregnant patients with dual HBV and HEV infection have shown a subclinical course. Immunosuppression is a risk factor for the development of chronic HEV infection, which can be managed by decreasing the dose of immune-suppressants and administering ribavirin. Vaccination for HEV has been developed and is in use in China but its efficacy in patients with CHB has yet to be established in the USA. In this review, we appraise studies on dual infection with HEV and HBV, including the effect of HEV superinfection and coinfection in CHB, management strategies used and the role of active vaccination in the prevention of HEV.
Collapse
Affiliation(s)
- Myra Nasir
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
- Correspondence to: Myra Nasir, Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA. Tel: +1-860-470-6616, E-mail:
| | - George Y. Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| |
Collapse
|
|
24
|
Oluremi AS, Opaleye OO, Ogbolu DO, Alli OAT, Ashiru FT, Alaka OO, Suleiman IE, Enitan SS, Adelakun AA, Adediji IO, Olowoyeye EA, Adewumi OO, Ayodele TO, Ogunleke OA. Serological evidence of HIV, Hepatitis B, C, and E viruses among liver disease patients attending tertiary hospitals in Osun State, Nigeria. J Immunoassay Immunochem 2020; 42:69-81. [PMID: 32967530 DOI: 10.1080/15321819.2020.1821214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Hepatitis infection in HIV positive individuals with liver diseases causes high mortality worldwide. HIV worsens the pathological effect of hepatitis viruses and potentiates reactivation of latent hepatitis infections due to reduced immunity. This research therefore aimed to study the occurrence of HIV and hepatitis viruses among liver diseases patients (LVDP) attending tertiary hospitals in Osun State, southwestern Nigeria. A total of 121 LVDP blood samples collected were tested for HIV and Hepatitis B, C, and E using and enzyme linked Immunossorbent assay (ELISA). Data were analyzed using packages within SPSS and P ≤ 0.05 was considered significant. Prevalence of 32.2%, 0.8%, 10.7%, and 18.2% for HBsAg, Anti-HCV, HEV-IgM, and HIV were found respectively. Marital status showed a significant association with HEV-IgM infection (χ2 = 9.869, P = .020). The prevalence of HBsAg, HEV, and HIV among LVDP in Osun State is alarming and health education among the patients and general populace is hereby advocated. High HEV-IgM seroprevalence implies that HEV routine screening should be incorporated into blood screening. Since HEV is associated with unhygienic practice, people should be enlightened on how to improve their living conditions.
Collapse
Affiliation(s)
- A S Oluremi
- Department of Medical Laboratory Science, Babcock University, Ilishan Remo, Nigeria.,Department of Medical Microbiology & Parasitology, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - O O Opaleye
- Department of Medical Microbiology & Parasitology, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - D O Ogbolu
- Department of Medical Laboratory Science, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - O A T Alli
- Department of Medical Laboratory Science, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - F T Ashiru
- Department of Medical Laboratory Science, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - O O Alaka
- Department of Medical Microbiology & Parasitology, Obafemi Awolowo University Teaching Hospital Complex, Ile Ife, Nigeria
| | - I E Suleiman
- Department of Chemical Pathology & Immunology, University of Ilorin Teaching Hospital, Ilorin, Nigeria
| | - S S Enitan
- Department of Medical Laboratory Science, Babcock University, Ilishan Remo, Nigeria
| | - A A Adelakun
- Department of Medical Laboratory Science, Babcock University, Ilishan Remo, Nigeria
| | - I O Adediji
- Department of Medical Laboratory Science, Babcock University, Ilishan Remo, Nigeria
| | - E A Olowoyeye
- Department of Basic Medical Sciences, College of Health Sciences & Technology, Ijero Ekiti, Nigeria
| | - O O Adewumi
- PPP Laboratory, University College Hospital, Ibadan, Nigeria
| | - T O Ayodele
- Department of Basic Medical Sciences, College of Health Sciences & Technology, Ijero Ekiti, Nigeria.,Department of Medical Laboratory Science, LAUTECH Teaching Hospital, Osogbo, Nigeria
| | - O A Ogunleke
- Department of Medical Laboratory Science, LAUTECH Teaching Hospital, Osogbo, Nigeria
| |
Collapse
|
|
25
|
Abstract
While the majority of worldwide hepatitis E viral (HEV) infections that occur in people are from contaminated water or food sources, there has also been a steadily rising number of reported cases of transfusion-transmitted HEV (TT-HEV) in blood donation recipients. For most, HEV infection is acute, self-limiting and asymptomatic. However, patients that are immunocompromised, especially transplant patients, are at much higher risk for developing chronic infections, which can progress to cirrhosis and liver failure, along with overall increased mortality. Because of the rising trend of HEV serological prevalence among the global population, and the fact that TT-HEV infection can cause serious clinical consequences among those patients most at need for blood donation, the need for screening for TT-HEV has been gaining in prominence as an important public health concern for both developing and developed countries. In the review, we summarise evidence for and notable cases of TT-HEV infections, the various aspects of HEV screening protocols and recent trends in the implementation of TT-HEV broad-based blood screening programmes.
Collapse
|
|
26
|
Ismail MB, Al Kassaa I, El Safadi D, Al Omari S, Mallat H, Dabboussi F, Hamze M. Prevalence of anti-hepatitis E virus IgG antibodies in sera from hemodialysis patients in Tripoli, Lebanon. PLoS One 2020; 15:e0233256. [PMID: 32421697 PMCID: PMC7233529 DOI: 10.1371/journal.pone.0233256] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 05/03/2020] [Indexed: 12/17/2022] Open
Abstract
Hepatitis E virus (HEV) is an important global public health concern. Several studies reported a higher HEV prevalence in patients undergoing regular hemodialysis (HD). In Lebanon, the epidemiology of HEV among HD patients has never been investigated previously. In this study, we examine the seroprevalence of HEV infection among 171 HD patients recruited from three hospital dialysis units in Tripoli, North Lebanon. Prevalence of anti-HEV IgG antibodies was evaluated in participant's sera using a commercial enzyme-linked immunosorbent assay (ELISA). The association of socio-demographic and clinical parameters with HEV infection in patients was also evaluated. Overall, 96 women and 75 men were enrolled in this study. Anti-HEV IgG antibodies were found positive in 37/171 HD patients showing a positivity rate of 21.63%. Among all examined variables, only the age of patients was significantly associated with seropositivity (P = 0.001). This first epidemiological study reveals a high seroprevalence of HEV infection among Lebanese HD patients. However, further evaluations that enroll larger samples and include control groups are required to identify exact causative factors of the important seropositivity rate in this population.
Collapse
Affiliation(s)
- Mohamad Bachar Ismail
- Laboratoire Microbiologie Santé et Environnement (LMSE), Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon
- Faculty of Science, Lebanese University, Tripoli, Lebanon
| | - Imad Al Kassaa
- Laboratoire Microbiologie Santé et Environnement (LMSE), Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon
| | - Dima El Safadi
- Laboratoire Microbiologie Santé et Environnement (LMSE), Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon
| | - Sarah Al Omari
- Faculty of Public Health, Lebanese University, Tripoli, Lebanon
| | - Hassan Mallat
- Laboratoire Microbiologie Santé et Environnement (LMSE), Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon
| | - Fouad Dabboussi
- Laboratoire Microbiologie Santé et Environnement (LMSE), Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon
| | - Monzer Hamze
- Laboratoire Microbiologie Santé et Environnement (LMSE), Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon
| |
Collapse
|
|
27
|
Halkurike VJ, Goel A, Katiyar H, Agarwal SK, Pande S, Aggarwal R. Blood transfusion is unlikely to be a source for hepatitis E virus transmission in India. Indian J Gastroenterol 2020; 39:161-164. [PMID: 32372189 DOI: 10.1007/s12664-020-01033-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 03/25/2020] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Transmission of hepatitis E virus (HEV) through transfusion has been reported from countries where genotype 3 virus is predominant. Data from countries with predominantly genotype 1 HEV, such as India, are limited. We studied the risk of HEV transmission following transfusion of blood or blood components in India. METHODS Adult patients undergoing cardiac surgery who received transfusion of blood or blood products in the peri-operative period and who lacked history of any transfusion or surgery in the preceding 1 year were studied. A pre-transfusion blood specimen was collected for IgG anti-HEV antibody test. For the participants who were seronegative for anti-HEV, follow up specimens were collected at every 2-3-month intervals for up to 6 months after surgery and were tested for IgM and IgG anti-HEV antibodies. RESULTS Of the 335 participants originally enrolled, 191 (57%) could be followed up. Of them, 103 (53.9%) were seropositive for HEV IgG at baseline and were excluded. Of the remaining 88 participants (age 42 ± 14.1 years; 55 [63%] male), none reported hepatitis-like illness during the follow up period of 81 ± 23 days. Also, none of these 88 participants was found to have seroconversion to anti-HEV IgM or IgG positivity in the follow up specimens. CONCLUSION Transfusion-mediated transmission of HEV was not observed in our cohort and may be infrequent in the Indian population, where genotype 1 is the predominant HEV type.
Collapse
Affiliation(s)
- Vijay J Halkurike
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Amit Goel
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Harshita Katiyar
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Surendra Kumar Agarwal
- Department of Cardiovascular and Thoracic Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Shantanu Pande
- Department of Cardiovascular and Thoracic Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India.
| |
Collapse
|
|
28
|
Hepatitis E Virus Infection in an Italian Cohort of Hematopoietic Stem Cell Transplantation Recipients: Seroprevalence and Infection. Biol Blood Marrow Transplant 2020; 26:1355-1362. [PMID: 32200124 DOI: 10.1016/j.bbmt.2020.03.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 01/15/2020] [Accepted: 03/10/2020] [Indexed: 01/05/2023]
Abstract
Chronic hepatitis E virus (HEV) infection in hematopoietic stem cell transplantation (HSCT) recipients is an emerging threat. The aim of this study was to provide data on the HEV burden in an Italian cohort of HSCT recipients and analyze risk factors for HEV seropositivity. This retrospective study reports data from 596 HSCT recipients compiled between 2010 and 2019. It included patients who underwent transplantation between 2010 and 2015 for whom pretransplantation (n = 419) and post-transplantation (n = 161) serum samples were available and tested retrospectively, as well as patients in whom prospective HEV testing was performed during the standard care: pre-HSCT IgG screening in 144, pre-HSCT HEV-RNA screening in addition to IgG screening in 60, and HEV-RNA testing in case of clinical suspicion of HEV infection in 59 (26 of whom were also included in the IgG screening cohorts). The rate of pre-HSCT HEV-IgG positivity was 6.0% (34 of 563). Older age was an independent risk factor for seropositivity (P = .039). None of the 34 HEV-IgG-positive patients had detectable HEV-RNA. One case of transient HEV-RNA positivity pre-HSCT was identified through screening. Two patients were diagnosed with chronic HEV hepatitis, and 1 patient was successfully treated with ribavirin. The burden of HEV infection in HSCT recipients in Italy is limited, and pre-HSCT screening appears to be of no benefit. Timely diagnosis of HEV infection with HEV-RNA is mandatory in cases of clinical suspicion.
Collapse
|
|
29
|
Fong IW. Blood Transfusion-Associated Infections in the Twenty-First Century: New Challenges. CURRENT TRENDS AND CONCERNS IN INFECTIOUS DISEASES 2020. [PMCID: PMC7120358 DOI: 10.1007/978-3-030-36966-8_8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Blood transfusions are vital components of modern medical treatment to which there is no viable alternative despite efforts to create artificial blood. Each year thousands of lives are saved by blood transfusions in every country of the world. However, blood and blood products can result in significant adverse events including immunologic reactions, infections, inefficacy, and others which can sometimes result in death and severe disability. Thus, the sustainability of safe blood systems and costs are considered to be at crisis level. In industrialized countries, the risk of transfusion-transmitted infections such as HIV, syphilis, hepatitis viruses B and C are very low [generally [<1 in a million units], but in developing countries [especially in Africa] blood safety is still not assured. Compounding the problem of blood/product safety with respect to infectious agents are new emerging infectious microbes that are not being routinely tested for in blood that are donated. This chapter reviews the infectious risk of blood transfusions, types, mode and geographic variation, and the methods being used by blood services to attenuate and prevent these risks.
Collapse
|
|
30
|
Niederhauser C, Widmer N, Hotz M, Tinguely C, Fontana S, Allemann G, Borri M, Infanti L, Sarraj A, Sigle J, Stalder M, Thierbach J, Waldvogel S, Wiengand T, Züger M, Gowland P. Current hepatitis E virus seroprevalence in Swiss blood donors and apparent decline from 1997 to 2016. ACTA ACUST UNITED AC 2019; 23. [PMID: 30180927 PMCID: PMC6124188 DOI: 10.2807/1560-7917.es.2018.23.35.1700616] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Hepatitis E virus (HEV) is a virus of emerging importance to transfusion medicine. Studies from several European countries, including Switzerland, have reported high seroprevalence of hepatitis E as a consequence of endemic infections. Published HEV seroprevalence estimates within developed countries vary considerably; primarily due to improved diagnostic assays. The purpose of this study was to investigate the seroprevalence of anti-HEV IgG in Swiss blood donations. Methods: We used the highly sensitive Wantai HEV IgG EIA and assessed regional distribution patterns. We analysed age- and sex-matched archive plasma dating back 20 years from canton Bern to investigate recent changes in HEV seroprevalence levels. Results: On average, 20.4% (95% confidence intervals: 19.1–21.8) of the 3,609 blood samples collected in 2014–16 were anti-HEV IgG positive; however, distinct differences between geographical regions were observed (range: 12.8–33.6%). Seroprevalence increased with age with 30.7% of males and 34.3% of women being positive donors over > 60 years old. Differences between sexes may be attributed to dissimilarities in the average age of this group. Within the specified region of the Bern canton, overall prevalence has declined over two decades from 30.3% in 1997/98 to 27.0% in 2006 and 22.3% in 2015/6. Conclusions: HEV seroprevalence in Switzerland is high, but has declined over the last decades. The result shows that primarily endemic HEV infections occur and that current blood products may pose a risk to vulnerable transfusion recipients. Nucleic acid screening of all blood products for HEV will begin in November 2018.
Collapse
Affiliation(s)
| | - Nadja Widmer
- Interregional Blood Transfusion SRC, Berne Switzerland
| | | | | | - Stefano Fontana
- Servizio Trasfusionale CRS della Svizzera Italiana, Lugano, Switzerland.,Interregional Blood Transfusion SRC, Berne Switzerland
| | | | - Mauro Borri
- Servizio Trasfusionale CRS della Svizzera Italiana, Lugano, Switzerland
| | - Laura Infanti
- Blood Transfusion Service Beider Basel, Basel, Switzerland
| | - Amira Sarraj
- Blood Transfusion Service SRC Neuchâtel/Jura, Neuchâtel, Switzerland
| | - Jörg Sigle
- Blood Transfusion Service SRC, Aargau/Solothurn, Switzerland
| | | | - Jutta Thierbach
- Blood Transfusion Service SRC Nordostschweiz, St. Gallen, Switzerland
| | | | - Tina Wiengand
- Blood Transfusion Service SRC Zentralschweiz, Luzern, Switzerland
| | - Max Züger
- Blood Transfusion Service SRC Thurgau, Münsterlingen, Switzerland
| | - Peter Gowland
- Interregional Blood Transfusion SRC, Berne Switzerland
| |
Collapse
|
|
31
|
Hofmeister MG, Foster MA, Teshale EH. Epidemiology and Transmission of Hepatitis A Virus and Hepatitis E Virus Infections in the United States. Cold Spring Harb Perspect Med 2019; 9:a033431. [PMID: 29712684 PMCID: PMC6444696 DOI: 10.1101/cshperspect.a033431] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
There are many similarities in the epidemiology and transmission of hepatitis A virus (HAV) and hepatitis E virus (HEV) genotype (gt)3 infections in the United States. Both viruses are enterically transmitted, although specific routes of transmission are more clearly established for HAV than for HEV: HAV is restricted to humans and primarily spread through the fecal-oral route, while HEV is zoonotic with poorly understood modes of transmission in the United States. New cases of HAV infection have decreased dramatically in the United States since infant vaccination was recommended in 1996. In recent years, however, outbreaks have occurred among an increasingly susceptible adult population. Although HEV is the most common cause of acute viral hepatitis in developing countries, it is rarely diagnosed in the United States.
Collapse
Affiliation(s)
- Megan G Hofmeister
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia 30329
- Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, Georgia 30329
| | - Monique A Foster
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia 30329
| | - Eyasu H Teshale
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia 30329
| |
Collapse
|
|
32
|
Hepatitis E Virus Infection in Lung Transplant Recipients: A Case Series. Transplant Proc 2019; 51:376-379. [DOI: 10.1016/j.transproceed.2018.10.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 10/23/2018] [Indexed: 01/05/2023]
|
|
33
|
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
|
|
34
|
Life cycle and morphogenesis of the hepatitis E virus. Emerg Microbes Infect 2018; 7:196. [PMID: 30498191 PMCID: PMC6265337 DOI: 10.1038/s41426-018-0198-7] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Revised: 11/01/2018] [Accepted: 11/05/2018] [Indexed: 12/19/2022]
Abstract
Hepatitis E virus (HEV) is transmitted primarily via contaminated water and food by the fecal oral route and causes epidemics in developing countries. In industrialized countries, zoonotic transmission of HEV is prevalent. In addition, HEV is the major cause of acute hepatitis in healthy adults and can cause chronic hepatitis in immunocompromised patients, with pregnant HEV-infected women having increased mortality rates of approximately 25%. HEV was once an understudied and neglected virus. However, in recent years, the safety of blood products with respect to HEV has increasingly been considered to be a public health problem. The establishment of HEV infection models has enabled significant progress to be made in understanding its life cycle. HEV infects cells via a receptor (complex) that has yet to be identified. The HEV replication cycle is initiated immediately after the (+) stranded RNA genome is released into the cell cytosol. Subsequently, infectious viral particles are released by the ESCRT complex as quasi-enveloped viruses (eHEVs) into the serum, whereas feces and urine contain only nonenveloped infectious viral progeny. The uncoating of the viral envelope takes place in the biliary tract, resulting in the generation of a nonenveloped virus that is more resistant to environmental stress and possesses a higher infectivity than that of eHEV. This review summarizes the current knowledge regarding the HEV life cycle, viral morphogenesis, established model systems and vaccine development.
Collapse
|
|
35
|
Todt D, Meister TL, Steinmann E. Hepatitis E virus treatment and ribavirin therapy: viral mechanisms of nonresponse. Curr Opin Virol 2018; 32:80-87. [PMID: 30384328 DOI: 10.1016/j.coviro.2018.10.001] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 09/27/2018] [Accepted: 10/04/2018] [Indexed: 02/07/2023]
Abstract
Hepatitis E virus (HEV) can cause chronic infections in immunosuppressed patients with adverse clinical outcomes. Intervention strategies are limited with ribavirin (RBV) being the only main therapeutic option as off-label drug. Recent reports on RBV monotherapy failures show a coherence with the presence of certain single nucleotide variants (SNVs) and in-frame insertions in the hypervariable region of open reading frame 1 in the HEV genome. Importantly, some of the alterations were present in the viral population as minor variant before RBV administration. Individualized infection medicine by early detection of emerging viral variants in patients could improve treatment outcome and prognosis.
Collapse
Affiliation(s)
- Daniel Todt
- Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany
| | - Toni Luise Meister
- Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany
| | - Eike Steinmann
- Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany.
| |
Collapse
|
|
36
|
Al-Absi ES, Al- Sadeq DW, Younis MH, Yassine HM, Abdalla OM, Mesleh AG, Hadwan TA, Amimo JO, Thalib L, Nasrallah GK. Performance evaluation of five commercial assays in assessing seroprevalence of HEV antibodies among blood donors. J Med Microbiol 2018; 67:1302-1309. [DOI: 10.1099/jmm.0.000807] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Enas S. Al-Absi
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
- 2Biomedical Research Center, Qatar University, Doha, Qatar
| | - Duaa W. Al- Sadeq
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Manaf H. Younis
- 3Department of Public Health, College of Health Sciences, Qatar University, Doha, Qatar
| | | | - Omnya M. Abdalla
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Areej G. Mesleh
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Tameem A. Hadwan
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Joshua O. Amimo
- 4Department of Animal Production, Faculty of Veterinary Medicine University of Nairobi, Nairobi, Kenya
- 5Bioscieces of Eastern and Central Africa-International Livestock Research Institute (BecA-ILRI), Nairobi, Kenya
| | - Lukman Thalib
- 5Bioscieces of Eastern and Central Africa-International Livestock Research Institute (BecA-ILRI), Nairobi, Kenya
| | - Gheyath K. Nasrallah
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
- 2Biomedical Research Center, Qatar University, Doha, Qatar
| |
Collapse
|
|
37
|
Transmission of Hepatitis E Virus With Plasma Exchange in Kidney Transplant Recipients. Transplantation 2018; 102:1351-1357. [PMID: 29561324 DOI: 10.1097/tp.0000000000002185] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
|
|
38
|
Katiyar H, Goel A, Sonker A, Yadav V, Sapun S, Chaudhary R, Aggarwal R. Prevalence of hepatitis E virus viremia and antibodies among healthy blood donors in India. Indian J Gastroenterol 2018; 37:342-346. [PMID: 30159666 DOI: 10.1007/s12664-018-0880-7] [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: 06/18/2018] [Accepted: 08/03/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatitis E virus (HEV) is transmitted primarily through contaminated water and food. Recently, HEV viremia in blood donors and transfusion-related transmission of HEV have been reported, leading to calls to screen donated blood for this virus. However, these data are from regions where genotype 3 HEV is predominant. In India, where human infections are caused only by genotype 1 HEV, the frequency of subclinical HEV viremia is unknown. METHODS Minipools of sera prepared from three donor units each from our institution's blood bank in Lucknow, India, were tested for HEV RNA using a sensitive amplification-based assay. A randomly selected subset was also tested for IgG anti-HEV antibodies using a commercial (Wantai) immunoassay. RESULTS Sera from 1799 donors (median [range] age 30 [18-63] years; 1746 [97.0%] men) were collected (June-July 2016, 900; November-December 2016, 899). Of these, 17 (0.95%), 16 (0.90%), and 3 (0.17%) tested positive for HBsAg, anti-HCV, and anti-HIV antibodies, respectively. None of the donors tested positive for HEV RNA. Of 633 randomly selected donors (age 30 [18-63] years, 613 [96.8%] male) tested for IgG anti-HEV, 383 (60.5%) tested positive. Seropositivity rate increased with age, being 70/136 (52%), 177/299 (59%), 100/154 (65%), 30/34 (88%), and 6/10 (60%) in the 18-24, 25-34, 35-44, 45-54, and 55 years or older age groups, respectively. CONCLUSIONS In healthy blood donors from northern India, HEV viremia is infrequent though anti-HEV antibody prevalence is high. This suggests that asymptomatic HEV viremia may be less frequent in areas with genotype 1 predominance than those with genotype 3 predominance.
Collapse
Affiliation(s)
- Harshita Katiyar
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Amit Goel
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Atul Sonker
- Department of Transfusion Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Vishwajeet Yadav
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Sadul Sapun
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Rajendra Chaudhary
- Department of Transfusion Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India.
| |
Collapse
|
|
39
|
Gupta E, Agarwala P. Hepatitis E Virus Infection: An Old Virus with a New Story! Indian J Med Microbiol 2018; 36:317-323. [DOI: 10.4103/ijmm.ijmm_18_149] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
|
|
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
|
Harrison L, DiCaprio E. Hepatitis E Virus: An Emerging Foodborne Pathogen. FRONTIERS IN SUSTAINABLE FOOD SYSTEMS 2018. [DOI: 10.3389/fsufs.2018.00014] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
|
|
42
|
Monteserín Ron L, Jiménez Palacios M, Linares Torres P, Miguel Peña A, Álvarez Cuenllas B, Fernández-Natal MI, Valverde Romero E, Jorquera Plaza F. Autochthonous acute hepatitis E: an increasingly frequent diagnosis. Clinical-epidemiological analysis of our experience. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2018; 109:344-349. [PMID: 28376624 DOI: 10.17235/reed.2017.4258/2016] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND In Europe, acute hepatitis caused by the hepatitis E virus (HEV) traditionally was an infection found in people who had travelled to endemic zones, mainly Asia and Africa. However, a growing number of sporadic autochthonous cases are now being diagnosed in the Western world. OBJECTIVE To analyze the cases of acute HEV hepatitis diagnosed in our setting, with the identification of the clinical-epidemiological characteristics. MATERIAL AND METHODS We included the cases of acute HEV hepatitis diagnosed (positive anti-HEV IgM and/or HEV RNA present in serum) between January 2008 and December 2014. Different clinical, epidemiological and evolutive parameters were analyzed. RESULTS A total of 23 patients were identified, all originating from Spain. Fourteen cases (60.87%) presented jaundice and marked cytolysis at the time of diagnosis (aspartate aminotransferase [AST] 1,106.91 U/l and alanine aminotransferase [ALT] 1,407.04 U/l). Twenty-two cases were regarded as autochthonous, and one patient had travelled to China three months before. The mean time to resolution was 11.2 weeks. Some autoimmune markers were positive in 43.5% of the patients. Two subjects were diagnosed with previous chronic liver disease and were classified as "acute-on-chronic liver failure" (ACLF), one died and the other underwent liver transplantation. CONCLUSION Acute HEV hepatitis in our setting is an autochthonous condition that is probably underdiagnosed, manifesting with jaundice and cytolysis. Autoimmune marker positivity is an epiphenomenon, which in some cases complicates the diagnosis.
Collapse
|
|
43
|
Al-Sadeq DW, Majdalawieh AF, Mesleh AG, Abdalla OM, Nasrallah GK. Laboratory challenges in the diagnosis of hepatitis E virus. J Med Microbiol 2018; 67:466-480. [PMID: 29485390 DOI: 10.1099/jmm.0.000706] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Hepatitis E virus (HEV) is an RNA virus that is an important cause of both acute and chronic hepatitis worldwide. To date, there are eight HEV genotypes that can infect mammals. HEV-1 and HEV-2 infect exclusively humans, while HEV-3 and HEV-4 infect humans and various animals, mainly pigs and deer. Additionally, two new genotypes (HEV-5 and HEV-6) infect mainly wild boar. Recently, newly discovered genotypes HEV-7 and HEV-8 were found to infect camels and possibly humans. Nevertheless, the epidemiological distribution of HEV-7 is not well established. HEV-8 is another newly discovered genotype that was identified in 2016 in Chinese Bactrian camels. Although faecal-oral transmission is the most common route of HEV transmission, HEV can be vertically transmitted from infected mothers to their fetuses. HEV may also spread by zoonotic transmission from infected animals to humans and through person-to-person contact. Nowadays, since the number of reported cases linked to blood donations is increasing annually, HEV is recognized as a transfusion-transmitted virus. Laboratory diagnostic techniques vary in their specificity and sensitivity for HEV detection. Direct techniques allow for detection of the viral proteins, antigens and viral nucleic acid, while HEV-specific IgG and IgM antibodies can help establish a diagnosis in acute and chronic infections. In this review, we will discuss recent technologies in the laboratory diagnosis of HEV, including serological and molecular methods to assess the specificity and sensitivity of currently available HEV commercial assays.
Collapse
Affiliation(s)
- Duaa W Al-Sadeq
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Amin F Majdalawieh
- Department of Biology, Chemistry and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, Sharjah, UAE
| | - Areej G Mesleh
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Omnya M Abdalla
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Gheyath K Nasrallah
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar.,Biomedical Research Center, Qatar University, Doha, Qatar
| |
Collapse
|
|
44
|
De Winter BCM, Hesselink DA, Kamar N. Dosing ribavirin in hepatitis E-infected solid organ transplant recipients. Pharmacol Res 2018; 130:308-315. [PMID: 29499270 DOI: 10.1016/j.phrs.2018.02.030] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Revised: 02/06/2018] [Accepted: 02/26/2018] [Indexed: 12/22/2022]
Abstract
Hepatitis E virus (HEV) is the most common cause of viral hepatitis worldwide. Genotypes 1 and 2 (GT1 and GT2) are mainly present in developing countries, while GT3 and GT4 are prevalent in developed and high-income countries. In the majority of cases, HEV causes a self-limiting hepatitis. GT3 and GT4 can be responsible for a chronic hepatitis that can lead to cirrhosis in immunocompromized patients, i.e. solid-organ- and stem-cell-transplant-patients, human immunodeficiency virus-infected patients, and patients receiving chemotherapy or immunotherapy. HEV has also been associated with extra-hepatic manifestations such as neurologic disorders (Guillain-Barré Syndrome and neuralgic amyotrophy) and kidney disease. In patients with chronic hepatitis, reduction of immunosuppression, when possible, is the first therapeutic option. In the remaining patients, ribavirin therapy has been shown to very efficient for treating HEV infection leading to a sustained virological response in nearly 80-85% of patients. However, the mechanism of action of ribavirin in this setting is still unknown, as is the impact of HEV RNA polymerase mutations. There are unmet needs with regard to the treatment of chronic HEV with ribavirin. These include the optimal dosing and duration of treatment, and the potential beneficial effects of therapeutic drug monitoring on the virological response and the incidence of side effects. In the present review, we will provide an overview of HEV epidemiology, its mode of transmission and clinical manifestations, as well as its treatment by ribavirin with a focus on the drug's pharmacokinetics and dosing.
Collapse
Affiliation(s)
- Brenda C M De Winter
- Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, The Netherlands
| | - Dennis A Hesselink
- Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, The Netherlands; Rotterdam Transplant Group, Division of Nephrology and Organ Transplantation, CHU Rangueil, INSERM U1043, IFR-BMT, Université Paul Sabatier, Toulouse, France
| | - Nassim Kamar
- Department of Internal Medicine, Division of Nephrology and Organ Transplantation, CHU Rangueil, INSERM U1043, IFR-BMT, Université Paul Sabatier, Toulouse, France.
| |
Collapse
|
|
45
|
Izopet J. [HEV and transfusion-recipient risk]. ANNALES PHARMACEUTIQUES FRANÇAISES 2018; 76:89-96. [PMID: 29395014 DOI: 10.1016/j.pharma.2017.12.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 12/18/2017] [Indexed: 02/06/2023]
Abstract
HEV infections are mainly food- and water-borne but transfusion-transmission has occurred in both developing and developed countries. The infection is usually asymptomatic but it can lead to fulminant hepatitis in patients with underlying liver disease and pregnant women living in developing countries. It also causes chronic hepatitis E, with progressive fibrosis and cirrhosis, in approximately 60 % of immunocompromised patients infected with HEV genotype 3. Extra-hepatic manifestations such as neurological and renal manifestations have been reported. The risk of a transfusion-transmitted HEV infection is linked to the frequency of viremia in blood donors, the donor virus load and the volume of plasma in the final transfused blood component. Several developed countries have adopted measures to improve blood safety based on the epidemiology of HEV.
Collapse
Affiliation(s)
- J Izopet
- Laboratoire de virologie, centre national de référence virus des hépatites à transmission entérique (hépatites A et E), institut fédératif de biologie, CHU de Purpan, 330, avenue de Grande-Bretagne, TSA 40031, 31059 Toulouse, France; Inserm U1043/CNRS 5282, université Paul-Sabatier, centre de physiopathologie de Toulouse-Purpan, 31024 Toulouse cedex 03, France.
| |
Collapse
|
|
46
|
Dreier J, Knabbe C, Vollmer T. Transfusion-Transmitted Hepatitis E: NAT Screening of Blood Donations and Infectious Dose. Front Med (Lausanne) 2018; 5:5. [PMID: 29450199 PMCID: PMC5799287 DOI: 10.3389/fmed.2018.00005] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2017] [Accepted: 01/09/2018] [Indexed: 01/05/2023] Open
Abstract
The risk and importance of transfusion-transmitted hepatitis E virus (TT-HEV) infections by contaminated blood products is currently a controversial discussed topic in transfusion medicine. The infectious dose, in particular, remains an unknown quantity. In the present study, we illuminate and review this aspect seen from the viewpoint of a blood donation service with more than 2 years of experience in routine HEV blood donor screening. We systematically review the actual status of presently known cases of TT-HEV infections and available routine NAT-screening assays. The review of the literature revealed a significant variation regarding the infectious dose causing hepatitis E. We also present the outcome of six cases confronted with HEV-contaminated blood products, identified by routine HEV RNA screening of minipools using the highly sensitive RealStar HEV RT-PCR Kit (95% LOD: 4.7 IU/mL). Finally, the distribution of viral RNA in different blood components [plasma, red blood cell concentrate (RBC), platelet concentrates (PC)] was quantified using the first WHO international standard for HEV RNA for NAT-based assays. None of the six patients receiving an HEV-contaminated blood product from five different donors (donor 1: RBC, donor 2–5: APC) developed an acute hepatitis E infection, most likely due to low viral load in donor plasma (<100 IU/mL). Of note, the distribution of viral RNA in blood components depends on the plasma content of the component; nonetheless, HEV RNA could be detected in RBCs even when low viral plasma loads of 100–1,000 IU/mL are present. Comprehensive retrospective studies of TT-HEV infection offered further insights into the infectivity of HEV RNA-positive blood products. Minipool HEV NAT screening (96 samples) of blood donations should be adequate as a routine screening assay to identify high viremic donors and will cover at least a large part of viremic phases.
Collapse
Affiliation(s)
- Jens Dreier
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein- Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - Cornelius Knabbe
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein- Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| | - Tanja Vollmer
- Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein- Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
| |
Collapse
|
|
47
|
Abstract
Hepatitis E virus (HEV) infection can lead to acute and chronic hepatitis as well as to extrahepatic manifestations such as neurological and renal disease; it is the most common cause of acute viral hepatitis worldwide. Four genotypes are responsible for most infection in humans, of which HEV genotypes 1 and 2 are obligate human pathogens and HEV genotypes 3 and 4 are mostly zoonotic. Until quite recently, HEV was considered to be mainly responsible for epidemics of acute hepatitis in developing regions owing to contamination of drinking water supplies with human faeces. However, HEV is increasingly being recognized as endemic in some developed regions. In this setting, infections occur through zoonotic transmission or contaminated blood products and can cause chronic hepatitis in immunocompromised individuals. HEV infections can be diagnosed by measuring anti-HEV antibodies, HEV RNA or viral capsid antigen in blood or stool. Although an effective HEV vaccine exists, it is only licensed for use in China. Acute hepatitis E is usually self-limiting and does not require specific treatment. Management of immunocompromised individuals involves lowering the dose of immunosuppressive drugs and/or treatment with the antiviral agent ribavirin.
Collapse
|
|
48
|
Al-Sadeq DW, Majdalawieh AF, Nasrallah GK. Seroprevalence and incidence of hepatitis E virus among blood donors: A review. Rev Med Virol 2017; 27:e1937. [PMID: 28876496 DOI: 10.1002/rmv.1937] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 07/16/2017] [Accepted: 07/18/2017] [Indexed: 12/19/2022]
Abstract
Hepatitis E virus (HEV) is an RNA virus with 4 main genotypes. HEV-1 and HEV-2 infect solely humans, while HEV-3 and HEV-4 infect humans and various animals such as pigs, deer, and rabbits. HEV-5 and HEV-6 infect mainly wild boar. Recently, new genotypes, known as HEV-7 and HEV-8, were found to infect camels and humans. HEV is globally distributed into different epidemiological patterns based on socioeconomic factors and ecology. Although HEV is mainly transmitted through the fecal-oral route, it was also recognized as a transfusion-transmitted virus. Transmission through blood donation was documented worldwide with rising annual observations, accounting for more than 2.5% of all transmissions. HEV infection is usually asymptomatic or subclinical in immunocompetent individuals, so it remains questionable whether there is an urgent need to screen for HEV prior to blood transfusion. Moreover, recent studies conducted in the Middle East and North Africa (MENA) region indicate that HEV is highly endemic. Here, we provide a review on HEV epidemiology, transmission, and laboratory diagnosis, giving special emphasis to the newly discovered genotypes, HEV-7 and HEV-8. Furthermore, we underscore the findings of recent HEV seroprevalence and viremia studies among blood donors worldwide. We also shed light on similar studies performed among blood donors in the MENA region.
Collapse
Affiliation(s)
- Duaa W Al-Sadeq
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Amin F Majdalawieh
- Department of Biology, Chemistry, and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, Sharjah, United Arab Emirates
| | - Gheyath K Nasrallah
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
- Biomedical Research Center, Qatar University, Doha, Qatar
| |
Collapse
|
|
49
|
Ankcorn MJ, Tedder RS. Hepatitis E: the current state of play. Transfus Med 2017; 27:84-95. [PMID: 28382704 DOI: 10.1111/tme.12405] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 11/08/2016] [Accepted: 02/22/2017] [Indexed: 12/16/2022]
Abstract
The hepatitis E virus (HEV) is a major cause of acute hepatitis globally. Genotypes 1 and 2 (G1 and G2) are obligate human pathogens transmitted faeco-orally, leading to epidemics in developing countries. In contrast, genotypes 3 and 4 (G3 and G4) have a wider host range, including humans, but are primarily porcine viruses and are transmitted from animals to humans as a food-borne zoonosis when meat from an infected animal is consumed. HEV is increasingly recognised as a problem in developed countries, including countries in Europe. G3 HEV is now the most common cause of acute viral hepatitis in the UK and cases continue to rise. The majority of these infections are acquired within the UK and thought to be from insufficiently cooked meat, predominantly processed pork meat. Previously thought to only cause self-limiting disease, HEV infection can persist in immunosuppressed patients, which may lead to chronic hepatitis and the rapid development of cirrhosis. Of particular interest to the transfusion community has been the possibility of transfusion-transmitted HEV, which has been reported from countries classically considered HEV-endemic but also non-endemic countries in Europe and Japan. This has prompted some countries to introduce screening for HEV in blood donations.
Collapse
Affiliation(s)
- M J Ankcorn
- Blood Borne Virus Unit, Virus Reference Department, National Infection Service, Public Health England, London, UK.,Transfusion Microbiology, National Health Service Blood and Transplant, London, UK
| | - R S Tedder
- Blood Borne Virus Unit, Virus Reference Department, National Infection Service, Public Health England, London, UK.,Transfusion Microbiology, National Health Service Blood and Transplant, London, UK
| |
Collapse
|
|
50
|
Izopet J, Lhomme S, Chapuy-Regaud S, Mansuy JM, Kamar N, Abravanel F. HEV and transfusion-recipient risk. Transfus Clin Biol 2017; 24:176-181. [PMID: 28690036 DOI: 10.1016/j.tracli.2017.06.012] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Accepted: 06/08/2017] [Indexed: 01/14/2023]
Abstract
HEV infections are mainly food- and water-borne but transfusion-transmission has occurred in both developing and developed countries. The infection is usually asymptomatic but it can lead to fulminant hepatitis in patients with underlying liver disease and pregnant women living in developing countries. It also causes chronic hepatitis E, with progressive fibrosis and cirrhosis, in approximately 60% of immunocompromised patients infected with HEV genotype 3. The risk of a transfusion-transmitted HEV infection is linked to the frequency of viremia in blood donors, the donor virus load and the volume of plasma in the final transfused blood component. Several developed countries have adopted measures to improve blood safety based on the epidemiology of HEV.
Collapse
Affiliation(s)
- J Izopet
- Department of virology, National reference center for hepatitis E virus, CHU Purpan, IFB, 330, avenue de Grande-Bretagne, TSA 40031, 31059 Toulouse, France; Inserm UMR 1043/CNRS UMR 5282, CPTP, center for pathophysiology of toulouse-Purpan, Toulouse university Paul-Sabatier, 31024 Toulouse, France.
| | - S Lhomme
- Department of virology, National reference center for hepatitis E virus, CHU Purpan, IFB, 330, avenue de Grande-Bretagne, TSA 40031, 31059 Toulouse, France; Inserm UMR 1043/CNRS UMR 5282, CPTP, center for pathophysiology of toulouse-Purpan, Toulouse university Paul-Sabatier, 31024 Toulouse, France
| | - S Chapuy-Regaud
- Department of virology, National reference center for hepatitis E virus, CHU Purpan, IFB, 330, avenue de Grande-Bretagne, TSA 40031, 31059 Toulouse, France; Inserm UMR 1043/CNRS UMR 5282, CPTP, center for pathophysiology of toulouse-Purpan, Toulouse university Paul-Sabatier, 31024 Toulouse, France
| | - J-M Mansuy
- Department of virology, National reference center for hepatitis E virus, CHU Purpan, IFB, 330, avenue de Grande-Bretagne, TSA 40031, 31059 Toulouse, France
| | - N Kamar
- Inserm UMR 1043/CNRS UMR 5282, CPTP, center for pathophysiology of toulouse-Purpan, Toulouse university Paul-Sabatier, 31024 Toulouse, France; Department of nephrology and organ transplantation, CHU Rangueil, 31059 Toulouse, France
| | - F Abravanel
- Department of virology, National reference center for hepatitis E virus, CHU Purpan, IFB, 330, avenue de Grande-Bretagne, TSA 40031, 31059 Toulouse, France; Inserm UMR 1043/CNRS UMR 5282, CPTP, center for pathophysiology of toulouse-Purpan, Toulouse university Paul-Sabatier, 31024 Toulouse, France
| |
Collapse
|