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Alexandrova R, Tsachev I, Kirov P, Abudalleh A, Hristov H, Zhivkova T, Dyakova L, Baymakova M. Hepatitis E Virus (HEV) Infection Among Immunocompromised Individuals: A Brief Narrative Review. Infect Drug Resist 2024; 17:1021-1040. [PMID: 38505248 PMCID: PMC10948336 DOI: 10.2147/idr.s449221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 02/21/2024] [Indexed: 03/21/2024] Open
Abstract
Hepatitis E virus (HEV) is a single-stranded positive-sense RNA virus that belongs to Hepeviridae family. HEV is the most common cause of acute viral hepatitis worldwide. According to the World Health Organization (WHO), there are estimated 20 million HEV infections worldwide every year, leading to estimated 3.3 million symptomatic cases of HEV infection. The WHO estimates that HEV infection caused approximately 44,000 deaths in 2015, which represents 3.3% of mortality rates due to viral hepatitis. In low-income (LI) countries and lower-middle-income (LMI) countries, HEV is a waterborne infection induced by HEV genotype (gt) 1 and HEV gt 2 that cause large outbreaks and affect young individuals with a high mortality rate in pregnant women from South Asian countries and patients with liver diseases. HEV gt 3, HEV gt 4, and HEV gt 7 are responsible for sporadic infections with zoonotic transmission mainly through the consumption of raw or undercooked meat from different animals. Acute HEV infection is relatively asymptomatic or mild clinical form, in rare cases the disease can be moderate/severe clinical forms and result in fulminant hepatitis or acute liver failure (ALF). Furthermore, HEV infection is associated with extrahepatic manifestations, including renal and neurological clinical signs and symptoms. Pregnant women, infants, older people, immunocompromised individuals, patients with comorbidities, and workers who come into close contact with HEV-infected animals are recognized as major risk groups for severe clinical form of HEV infection and fatal outcome. Chronic HEV infection can occur in immunocompromised individuals with the possibility of progression to cirrhosis.
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Affiliation(s)
- Radostina Alexandrova
- Department of Pathology, Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Ilia Tsachev
- Department of Microbiology, Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, Trakia University, Stara Zagora, Bulgaria
| | - Plamen Kirov
- Department of Pathology, Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Abedulkadir Abudalleh
- Department of Pathology, Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Hristo Hristov
- Department of Pathology, Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Tanya Zhivkova
- Department of Pathology, Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Lora Dyakova
- Department of Synaptic Signaling and Communication, Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Magdalena Baymakova
- Department of Infectious Diseases, Military Medical Academy, Sofia, Bulgaria
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Santos-Silva S, da Silva Dias Moraes DF, López-López P, Rivero-Juarez A, Mesquita JR, Nascimento MSJ. Hepatitis E Virus in the Iberian Peninsula: A Systematic Review. FOOD AND ENVIRONMENTAL VIROLOGY 2023; 15:193-211. [PMID: 37434079 PMCID: PMC10499749 DOI: 10.1007/s12560-023-09560-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 06/26/2023] [Indexed: 07/13/2023]
Abstract
One of the most frequent causes of acute viral hepatitis is hepatitis E virus (HEV) causing 20 million infections worldwide each year and 44,000 deaths. Studies on HEV in the Iberian Peninsula have been increasing through time with HEV infection being identified in humans and animals. The aim of the present systematic review was to compile and evaluate all the published data on HEV from studies performed in humans, animals and environmental samples in the Iberian Peninsula. The electronic databases Mendeley, PubMed, Scopus, and Web of Science were thoroughly searched, and research published up until February 01, 2023 were included. Resulting in a total of 151 eligible papers by full reading and application of PRISMA exclusion/inclusion criteria. Overall, the present review shows that several HEV genotypes, namely HEV-1, 3, 4, and 6 as well as Rocahepevirus, are circulating in humans, animals, and in the environment in the Iberian Peninsula. HEV-3 was the most common genotype circulating in humans in Portugal and Spain, as expected for developed countries, with HEV-1 only being detected in travelers and emigrants from HEV endemic regions. Spain is the biggest pork producer in Europe and given the high circulation of HEV in pigs, with HEV-3 being primarily associated to zoonotic transmission through consumption of swine meat and meat products, in our opinion, the introduction of an HEV surveillance system in swine and inclusion of HEV in diagnostic routines for acute and chronic human hepatitis would be important. Additionally, we propose that establishing a monitoring mechanism for HEV is crucial in order to gain a comprehensive understanding of the prevalence of this illness and the various strains present in the Iberian Peninsula, as well as their potential impact on public health.
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Affiliation(s)
- Sérgio Santos-Silva
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
| | | | - Pedro López-López
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Reina Sofía, Universidad de Córdoba, Córdoba, Spain
- CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
| | - António Rivero-Juarez
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Reina Sofía, Universidad de Córdoba, Córdoba, Spain
- CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
| | - João R Mesquita
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
- Epidemiology Research Unit (EPIUnit), Instituto de Saúde Pública da Universidade do Porto, Porto, Portugal.
- Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Porto, Portugal.
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Detection and characterization of hepatitis E virus genotype 3 in HIV-infected patients and blood donors from southern Brazil. Int J Infect Dis 2019; 86:114-121. [PMID: 31279609 DOI: 10.1016/j.ijid.2019.06.027] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 06/21/2019] [Accepted: 06/30/2019] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Hepatitis E virus genotype 3 (HEV-3) infection usually causes self-limited acute hepatitis. In immunosuppressed patients, HEV-3 infection can rapidly progress to chronic hepatitis and cirrhosis. In southern Brazil, data on HEV seroprevalence are scarce. METHODS Testing for HEV RNA and antibodies (anti-HEV) was performed for 320 HIV-infected patients followed at the HIV/AIDS Service of the Federal University of Rio Grande between 2012 and 2013, as well as 281 blood donor samples obtained in 2015. Variables associated with anti-HEV positivity were assessed by multivariable logistic regression analysis. RESULTS HIV and blood donor groups showed similar HEV seroprevalence (6.7% and 7.1%, respectively). Risk factors associated with anti-HEV detection were older age, marital status, a higher number of sexual partners, poor sanitation, and alcohol use (HIV group), and living in a rural area (blood donors). HEV RNA was detected in eight serum samples from HIV-infected patients and in one blood donor, who was also positive for anti-HEV IgM and IgG. CONCLUSIONS The prevalence rates of HEV infection were comparable between HIV-seropositive patients who were not severely immunocompromised and blood donors. The blood donor's HEV isolate showed high similarity with swine HEV strains from Brazilian herds in the same region, thus indicating a potential risk of foodborne and parenteral transmission via blood transfusion.
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Oikonomou KG, Tsai E, Sarpel D, Dieterich DT. Liver Disease in Human Immunodeficiency Virus Infection. Clin Liver Dis 2019; 23:309-329. [PMID: 30947879 DOI: 10.1016/j.cld.2018.12.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver disease in human immunodeficiency virus (HIV) remains a main cause of morbidity and mortality. Liver-related morbidity and mortality can be caused by multiple etiologic factors, including opportunistic infections, direct and indirect effects of antiretrovirals, direct and indirect effects of HIV, and viral hepatitides. These factors present with varied liver pathophysiologic mechanisms that lead to abnormalities in liver enzymes and synthetic function test, followed by distinct clinical presentations. This article elucidates the direct effects on HIV in the liver and explores the diagnostic and management challenges in patients with HIV in the era of highly active antiretroviral treatment.
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Affiliation(s)
- Katerina G Oikonomou
- Icahn School of Medicine at Mount Sinai, 1 Gustav L. Levy Place, New York, NY 10029-6574, USA.
| | - Eugenia Tsai
- Icahn School of Medicine at Mount Sinai, 1 Gustav L. Levy Place, New York, NY 10029-6574, USA
| | - Dost Sarpel
- Icahn School of Medicine at Mount Sinai, 1 Gustav L. Levy Place, New York, NY 10029-6574, USA
| | - Douglas T Dieterich
- Icahn School of Medicine at Mount Sinai, 1 Gustav L. Levy Place, New York, NY 10029-6574, USA
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Debes JD, Pas SD, Groothuismink ZMA, van der Ende ME, de Man RA, Boonstra A. A mutation in the progesterone receptor predisposes to HEV infection in HIV-positive patients. Liver Int 2018; 38:792-796. [PMID: 29285885 PMCID: PMC5947588 DOI: 10.1111/liv.13678] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Accepted: 12/15/2017] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND AIMS Infection with Hepatitis E virus (HEV) can cause chronic liver disease in immunocompromised hosts. In transplant recipients, the use of certain immunosuppressants and food habits has been proposed as risk factors for HEV. In individuals infected with the human immunodeficiency virus (HIV), risk factors for HEV infection are less clear. We aimed to study the association between a mutation in the progesterone receptor (PR) named PROGINS and HEV-infected in HIV-positive individuals. METHODS We evaluated the presence of the SNP PROGINS via KASP in serum samples of 64 HIV-positive individuals and 187 healthy controls. We performed ELISA tests to address the serum levels of IL-10 and IL-12, as well as T-cell stimulation assays in peripheral blood to address immune response in individuals with PROGINS. RESULTS We found a significant association between the presence of PROGINS mutation and HEV seroprevalence in individuals infected with HIV (30% in HIV+/HEV+ versus 2% in HIV+/HEV, respectively, P = .009). Moreover, we found that HIV+/HEV+ individuals expressing the PROGINS mutation had lower serum levels of IL-10 and higher levels of IL-12. The presence of the mutation led to a reduced response upon stimulation of CD4+ and CD8+ T cells compared to those without the mutation, suggesting an immune modulation associated with PROGINS. CONCLUSIONS Our study identified a mutation in the PR that provides significant insights into mechanisms of HEV infection in immunosuppressed individuals.
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Affiliation(s)
- Jose D. Debes
- Department of MedicineUniversity of MinnesotaMinneapolisMNUSA,Department of Gastroenterology and HepatologyErasmus MCUniversity Medical Center RotterdamRotterdamthe Netherlands
| | - Suzan D. Pas
- Department of VirologyErasmus MCUniversity Medical Center RotterdamRotterdamthe Netherlands
| | - Zwier M. A. Groothuismink
- Department of Gastroenterology and HepatologyErasmus MCUniversity Medical Center RotterdamRotterdamthe Netherlands
| | - Marchina E. van der Ende
- Department of Internal MedicineSection Infectious DiseasesErasmus MCUniversity Medical Center RotterdamRotterdamthe Netherlands
| | - Robert A. de Man
- Department of Gastroenterology and HepatologyErasmus MCUniversity Medical Center RotterdamRotterdamthe Netherlands
| | - Andre Boonstra
- Department of Gastroenterology and HepatologyErasmus MCUniversity Medical Center RotterdamRotterdamthe Netherlands
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Liver involvement in human immunodeficiency virus infection. Indian J Gastroenterol 2016; 35:260-73. [PMID: 27256434 DOI: 10.1007/s12664-016-0666-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Accepted: 05/01/2016] [Indexed: 02/04/2023]
Abstract
The advances in management of patients with acquired immunodeficiency syndrome (AIDS) with highly effective anti-retroviral therapy (HAART) have resulted in increased longevity of patients with human immunodeficiency virus (HIV) infection. AIDS-related illnesses now account for less than 50 % of the deaths, and liver diseases have emerged as the leading cause of death in patients with HIV infection. Chronic viral hepatitis, drug-related hepatotoxicity, non-alcoholic fatty liver disease, and opportunistic infections are the common liver diseases that are seen in HIV-infected individuals. Because of the shared routes of transmission, co-infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are very common in HIV-infected persons. Hepatitis C is the most common viral hepatitis seen in HIV-infected patients. With the availability of directly acting agents, treatment outcome of HCV is comparable to that seen in non HIV-infected patients. Careful monitoring is required for drug interactions and drug-induced hepatotoxicity and modification of drugs should be done where necessary. The results of liver transplantation in select HIV-infected patients can be comparable with those of HIV-negative patients.
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Debes JD, Pisano MB, Lotto M, Re V. Hepatitis E virus infection in the HIV-positive patient. J Clin Virol 2016; 80:102-6. [PMID: 27243210 DOI: 10.1016/j.jcv.2016.05.006] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Accepted: 05/16/2016] [Indexed: 12/12/2022]
Abstract
Hepatitis E virus (HEV) is a RNA virus that can cause hepatitis. In immunocompetent individuals, infection with HEV usually leads to asymptomatic seroconversion. However, in immunosuppressed patients, such as transplant recipients, HEV can develop into a chronic infection. Studies regarding the seroprevalence and clinical implications of HEV in patients infected with the human immunodeficiency virus (HIV) are conflicting. Levels of CD4 count in blood seem to be the most widely associated risk factor, while other factors such as meat consumption or proximity to animals are less clearly associated with HEV infection. Progression to chronicity, as well as extrahepatic manifestations of HEV seem rare in HIV, and the implications of HEV in liver disease progression are poorly understood in the HIV-infected. In this review we describe the epidemiology, risk factors, and clinical implications of HEV infection in individuals infected with HIV.
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Affiliation(s)
- Jose D Debes
- Department of Medicine, University of Minnesota, Minneapolis, MN, United States, United States.
| | - Maria Belen Pisano
- Instituto de Virología "Dr. J. M. Vanella" Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Argentina
| | - Martin Lotto
- Instituto de Virología "Dr. J. M. Vanella" Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Argentina
| | - Viviana Re
- Instituto de Virología "Dr. J. M. Vanella" Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Argentina
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Furukawa NW, Teshale EH, Cosmas L, Ochieng M, Gikunju S, Fields BS, Montgomery JM. Serologic evidence for hepatitis E virus infection among patients with undifferentiated acute febrile illness in Kibera, Kenya. J Clin Virol 2016; 77:106-8. [PMID: 26925954 DOI: 10.1016/j.jcv.2016.02.021] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Revised: 02/15/2016] [Accepted: 02/20/2016] [Indexed: 12/27/2022]
Abstract
BACKGROUND Hepatitis E (HEV) is an emerging cause of viral hepatitis mainly transmitted through the fecal-oral route. Residents of the Kibera slum of Nairobi, Kenya are at risk for fecal-orally transmitted infections. OBJECTIVE To quantify the incidence and prevalence of HEV infection among acute febrile illness (AFI) cases using a population-based infectious disease surveillance network. STUDY DESIGN Cross-sectional serum samples from AFI case-patients between 2009 and 2012 were matched to the age and gender distribution of the Kibera population and tested by IgM and IgG enzyme immunoassays (EIA) and nucleic acid testing (NAT). Serum from healthy residents was also tested by EIA. RESULTS Of the 482 AFI serum samples tested, 124 (25.7%) and 182 (37.8%) were IgM and IgG reactive, respectively. On multivariate analysis, IgM reactivity was associated with HIV (RR 1.66, 95%CI 1.07, 2.60; p=0.024) while IgG reactivity was associated with increasing age (p<0.001) and HIV (RR 1.93, 95%CI 1.52, 2.46; p<0.001). AFI case-patients were more likely to be IgM (p=0.002) and IgG (p<0.001) reactive compared to healthy residents. The seroincidence by HEV-specific IgM was 84.0 per 1000 person years, however, all 482 samples were negative by NAT. CONCLUSIONS Serologic evidence for HEV in Kibera suggests a high burden of infection, but NAT did not confirm HEV viremia. Additional testing is needed to determine whether EIAs are susceptible to false positivity in undifferentiated AFI populations before their widespread use.
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Affiliation(s)
- N W Furukawa
- Department of Medicine, University of Washington, Seattle, WA, USA.
| | - E H Teshale
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - L Cosmas
- Center for Global Health, Division of Global Health Protection, Centers for Disease Control and Prevention, Nairobi, Kenya
| | - M Ochieng
- Kenya Medical Research Institute, Center for Global Health Research, Nairobi, Kenya
| | - S Gikunju
- Kenya Medical Research Institute, Center for Global Health Research, Nairobi, Kenya
| | - B S Fields
- Center for Global Health, Division of Global Health Protection, Centers for Disease Control and Prevention, Nairobi, Kenya
| | - J M Montgomery
- Center for Global Health, Division of Global Health Protection, Centers for Disease Control and Prevention, Nairobi, Kenya
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Fierro NA, Realpe M, Meraz-Medina T, Roman S, Panduro A. Hepatitis E virus: An ancient hidden enemy in Latin America. World J Gastroenterol 2016; 22:2271-2283. [PMID: 26900289 PMCID: PMC4735001 DOI: 10.3748/wjg.v22.i7.2271] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Revised: 10/21/2015] [Accepted: 12/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) infection is a common cause of acute clinical hepatitis worldwide. HEV is an RNA-containing virus and the only member of the genus Hepevirus in the family Hepeviridae. Human HEV is classified into four genotypes widely distributed across the world. The virus is mainly transmitted via the fecal-oral route, and water-borne epidemics have become characteristic of hepatitis E in developing countries, including those in Latin America. The zoonotic potential of HEV is broadly recognized. Thus, there is an urgent need to re-evaluate virus transmission scenarios and to enforce epidemiological surveillance systems. Additionally, it is known that HEV infections, initially defined as self-limiting, can also take chronic courses in immunocompromised patients. Moreover, we recently reported a high seroprevalence of HEV in samples from cirrhotic patients with no other etiological agents present, suggesting the potential role of HEV in the development of chronic liver illness. In this review, HEV genomic variability, transmission, chronic infectious course, zoonotic potential and treatment are discussed. Focus is placed on the impact of HEV infection in Latin America, to support the development of specific control strategies and the handling of this important and typically imperceptible viral infection.
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