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Chhoung C, Ouoba S, Lingani M, Ko K, Phyo Z, Mirzaev UK, Yoshinaga Y, Akuffo GA, Sugiyama A, Akita T, Fukuma S, Tinto H, Takahashi K, Tanaka J. Weighted prevalence and associated risk factors of hepatitis E virus antibodies among pregnant women in rural Burkina Faso using dried blood spot samples. Hepatol Res 2025. [PMID: 40318091 DOI: 10.1111/hepr.14180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 01/30/2025] [Accepted: 02/20/2025] [Indexed: 05/07/2025]
Abstract
AIM To estimate the weighted prevalence of hepatitis E virus (HEV) antibodies and risk factors among pregnant women in Burkina Faso and to evaluate the efficiency of dried blood spots (DBS) in detecting HEV antibodies. METHODS We first evaluated the efficiency of DBS detecting HEV antibodies by comparing 62 DBS with matched serum samples using recomWell IgG and IgM kits (Mikrogen Diagnostik). Anti-HEV immunoglobulin G (IgG) and immunoglobulin M (IgM) were identified in 491 DBS samples collected from pregnant women in Burkina Faso using recomWell kits. HEV RNA was tested using HEV nested polymerase chain reaction among HEV-antibodies positive. The survey-weighted method was applied for prevalence calculations and risk factors analysis. RESULTS The detection of anti-HEV IgG and anti-HEV IgM in DBS samples revealed a sensitivity of 96.7% and 76.7% and a specificity of 100% and 93.8% compared to serum samples, respectively. Among 491 pregnant women tested, the weighted prevalence of anti-HEV IgG was 18.6%, and anti-HEV IgM was 2.5%, with no HEV RNA detected. A significant age-related increase was observed in the prevalence of anti-HEV IgG (p < 0.001), while no significant was found for anti-HEV IgM-positivity (p = 0.1451). Multiparity was significantly associated with anti-HEV IgG-positivity, while women aged 25-34 years were at higher risk of anti-HEV IgM-positivity. CONCLUSION This study revealed that DBS is a reliable alternative for HEV seroepidemiological studies, especially in resource-limited settings, although further investigation is needed for anti-HEV IgM detection. The weighted prevalence of anti-HEV IgG was 18.6% and anti-HEV IgM was 2.5%, highlighting the ongoing burden of HEV infection, particularly in high-risk groups like pregnant women in rural Burkina Faso.
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Affiliation(s)
- Chanroth Chhoung
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Serge Ouoba
- Unité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Sciences de La Santé (IRSS), Nanoro, Burkina Faso
| | - Moussa Lingani
- Unité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Sciences de La Santé (IRSS), Nanoro, Burkina Faso
| | - Ko Ko
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Zayar Phyo
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | | | - Yayoi Yoshinaga
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Golda Ataa Akuffo
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Aya Sugiyama
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Shingo Fukuma
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Halidou Tinto
- Unité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Sciences de La Santé (IRSS), Nanoro, Burkina Faso
| | - Kazuaki Takahashi
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
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Mor O, Na’amnih W, Shirazi R, Wax M, Gozlan Y, Kassim M, Sayid H, Omari A, Jabbor A, Muhsen K, Mari A. Hepatitis E virus (HEV) infection among the Arab population in Northern Israel: an insight into the seroepidemiology and associated risk factors. Epidemiol Infect 2025; 153:e10. [PMID: 39801356 PMCID: PMC11729521 DOI: 10.1017/s0950268824001407] [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: 03/21/2024] [Revised: 07/14/2024] [Accepted: 09/03/2024] [Indexed: 01/16/2025] Open
Abstract
Hepatitis E virus (HEV) is one of the most common causes of viral hepatitis. We examined HEV seroprevalence and associations of sociodemographic and lifestyle characteristics with HEV immunoglobulin G (IgG) seropositivity in the Arab population. A cross-sectional single-centre study was conducted among adults in the Nazareth area during 2022. Blood samples were tested using the Altona Real-Star HEV-RNA and the Wantai IgG assays. Data on sociodemographics, health status, and lifestyle were collected using structured questionnaires.Overall, 490 individuals (55.9% males) aged 18 - 96 (mean = 53.2, SD = 28.0) were enrolled. HEV IgG seropositivity was estimated at 21.4% (95% CI 17.9-25.3). No samples were HEV-RNA positive. The correlates of HEV IgG seropositivity were older age (prevalence ratio (PR) 1.07, 95% CI 1.04-1.09, P < 0.001) and consuming beef frequently (PR 2.81, 95% CI 1.40-5.63, P = 0.003). No associations were found between Arab religious groups (Muslim, Christian or Druze, representing different socioeconomic status and dietary habits) or pork consumption and HEV IgG seropositivity. In conclusion, HEV seropositivity was high in the Arab population, and assessing HEV in Ruminants, particularly cows, is warranted.
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Affiliation(s)
- Orna Mor
- Department of Epidemiology and Preventive Medicine, School of Public Health, Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Central Virology Laboratory, Ministry of Health, Public Health Services, The Chaim Sheba Medical Center, Tel HaShomer, Ramat-Gan, Israel
| | - Wasef Na’amnih
- Department of Epidemiology and Preventive Medicine, School of Public Health, Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Rachel Shirazi
- Central Virology Laboratory, Ministry of Health, Public Health Services, The Chaim Sheba Medical Center, Tel HaShomer, Ramat-Gan, Israel
| | - Marina Wax
- Central Virology Laboratory, Ministry of Health, Public Health Services, The Chaim Sheba Medical Center, Tel HaShomer, Ramat-Gan, Israel
| | - Yael Gozlan
- Central Virology Laboratory, Ministry of Health, Public Health Services, The Chaim Sheba Medical Center, Tel HaShomer, Ramat-Gan, Israel
| | - Marah Kassim
- Department of Epidemiology and Preventive Medicine, School of Public Health, Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Helal Sayid
- Gastroenterology Department, Nazareth Hospital EMMS, Azrieli Faculty of Medicine, Bar Ilan University, Ramat-Gan, Israel
| | - Ali Omari
- Gastroenterology Department, Nazareth Hospital EMMS, Azrieli Faculty of Medicine, Bar Ilan University, Ramat-Gan, Israel
| | - Adel Jabbor
- Medical Laboratory, Nazareth Hospital EMMS, Nazareth, Israel
| | - Khitam Muhsen
- Department of Epidemiology and Preventive Medicine, School of Public Health, Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Amir Mari
- Gastroenterology Department, Nazareth Hospital EMMS, Azrieli Faculty of Medicine, Bar Ilan University, Ramat-Gan, Israel
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Papageorgiou D, de Lastic AL, Tsachouridou O, Metallidis S, Akinosoglou K. HEV Infection in Beta-Thalassemia Patients. Pathogens 2024; 13:1058. [PMID: 39770318 PMCID: PMC11728467 DOI: 10.3390/pathogens13121058] [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: 10/10/2024] [Revised: 11/17/2024] [Accepted: 11/28/2024] [Indexed: 01/14/2025] Open
Abstract
Thalassemia is an inherited hematological disorder characterized by a decrease in the synthesis of or absence of one or more globin chains. Hepatitis E virus (HEV) is a major cause of acute viral hepatitis, constituting a major global health burden and emerging as a critical public health concern. HEV infection is mainly transmitted via the fecal-oral route; however, parenteral transmission through blood components has been reported in both developing and developed countries. Although HEV infection is typically self-limiting, immunocompromised individuals, patients with chronic liver disease, and thalassemic patients are at a heightened risk of contracting the infection and may develop chronic hepatitis and life-threatening complications that require treatment. The reported prevalence rates of HEV in thalassemia patients vary significantly by country. Age, gender, residential area, and the cumulative amount of blood transfusions received have been identified as associated risk factors for HEV infection. In order to enhance blood safety and ensure the protection of vulnerable patient populations, such as thalassemia patients, several countries have introduced universal or targeted HEV screening policies in blood donations. Other preventive measures include vigilant monitoring of thalassemic patients and screening for anti-HEV antibodies. The aim of this review is to explore the prevalence, risk factors, clinical impact and management of HEV infection in patients with thalassemia.
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Affiliation(s)
| | - Anne-Lise de Lastic
- Laboratory of Immunohematology, Medical School, University of Patras, Rio, 26504 Patras, Greece;
| | - Olga Tsachouridou
- Department of Internal Medicine and Infectious Diseases, AHEPA Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (O.T.); (S.M.)
| | - Simeon Metallidis
- Department of Internal Medicine and Infectious Diseases, AHEPA Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (O.T.); (S.M.)
| | - Karolina Akinosoglou
- Medical School, University of Patras, Rio, 26504 Patras, Greece;
- Department of Internal Medicine and Infectious Diseases, University General Hospital of Patras, Rio, 26504 Patras, Greece
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Huang X, Zheng X, Chen L, Zhuang C, Yang C, Zang X, Wang Y, Jiang H, Huang X, Yan Q, Tang Z, Su Y, Zheng Z, Wu T, Zhang X, Huang Y, Huang S, Zhu F, Zhang J, Xia N. Active surveillance of hepatitis E: a 10-year epidemiological analysis in a city in eastern China. Emerg Microbes Infect 2024; 13:2373315. [PMID: 38922438 PMCID: PMC11257014 DOI: 10.1080/22221751.2024.2373315] [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: 01/23/2024] [Accepted: 06/22/2024] [Indexed: 06/27/2024]
Abstract
Hepatitis E virus (HEV) is an important cause of acute hepatitis, however, is highly neglected and largely underreported. This study aimed to describe the detailed epidemiology of hepatitis E (HE) through a 10-year surveillance. A community-based active hepatitis surveillance was conducted between November 2007 and October 2017 in 11 townships of Dongtai City in China, involving 355,673 residents. Serum samples were obtained from patients presenting with hepatitis symptoms for more than 3 days. Serum alanine aminotransferase (ALT) levels greater than 2.5 times the upper limit of normal (ULN) were considered acute hepatitis. Samples were subsequently tested for IgG and IgM anti-HEV antibodies, HEV RNA, and hepatitis B surface antigen (HBsAg). The data indicated the incidence of HE fluctuated downward from 2007 to 2017, with an average annual age-standardized incidence of 17.50 per 100,000, exceeding the 10.26 per 100,000 in the National Notifiable Disease Report System (NNDRS). The incidence was notably higher among males (20.95 per 100,000) and individuals aged 50-69 years (37.47 per 100,000). Genotype 4 (HEV-4) was the predominantly circulating genotype during the study period. Furthermore, the study revealed the incidence of hepatitis with HEV and hepatitis B virus (HBV) co-infection was 4.99 per 100,000. The active surveillance system identified a higher incidence of HE compared to NNDRS, with a decreased prevalence over a 10-year period. While efforts are still needed to prevent HE in high-risk populations, including individuals with hepatitis B and the elderly.
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Affiliation(s)
- Xingcheng Huang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, People’s Republic of China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, People’s Republic of China
| | - Xiaoxiang Zheng
- Dongtai Center for Disease Control and Prevention, Dongtai, People’s Republic of China
| | - Lin Chen
- Dongtai Center for Disease Control and Prevention, Dongtai, People’s Republic of China
| | - Chunlan Zhuang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, People’s Republic of China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, People’s Republic of China
| | - Changlin Yang
- Dongtai Center for Disease Control and Prevention, Dongtai, People’s Republic of China
| | - Xia Zang
- Dongtai Center for Disease Control and Prevention, Dongtai, People’s Republic of China
| | - Yijun Wang
- Dongtai Center for Disease Control and Prevention, Dongtai, People’s Republic of China
| | - Hanmin Jiang
- Dongtai Center for Disease Control and Prevention, Dongtai, People’s Republic of China
| | - Xiaomeng Huang
- Dongtai Center for Disease Control and Prevention, Dongtai, People’s Republic of China
| | - Qiang Yan
- Xiamen Innodx Biotech Company, Xiamen, People’s Republic of China
| | - Zimin Tang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, People’s Republic of China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, People’s Republic of China
| | - Yingying Su
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, People’s Republic of China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, People’s Republic of China
| | - Zizheng Zheng
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, People’s Republic of China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, People’s Republic of China
| | - Ting Wu
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, People’s Republic of China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, People’s Republic of China
| | - Xuefeng Zhang
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of China
| | - Yue Huang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, People’s Republic of China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, People’s Republic of China
| | - Shoujie Huang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, People’s Republic of China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, People’s Republic of China
| | - Fengcai Zhu
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of China
| | - Jun Zhang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, People’s Republic of China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, People’s Republic of China
| | - Ningshao Xia
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, People’s Republic of China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, People’s Republic of China
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Ribeiro LB, Reche LA, Nastri ACDSS, Malta FDM, Amgarten DE, Casadio LVB, Gonzalez MP, Ono SK, Mendes-Correa MC, Carrilho FJ, Pinho JRR, Gomes-Gouvêa MS. Acute Hepatitis Related to Hepatitis E Virus Genotype 3f Infection in Brazil. J Med Virol 2024; 96:e70024. [PMID: 39530268 DOI: 10.1002/jmv.70024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 09/27/2024] [Accepted: 10/12/2024] [Indexed: 11/16/2024]
Abstract
The hepatitis E virus (HEV) is an important causative agent of acute hepatitis (AH). Despite reports of human infection in Brazil, the investigation is not routinely conducted, even in cases of elevated liver enzymes. This study evaluated two groups: group 1-patients with acute hepatitis A (n = 44); group 2-patients with nonA-C AH (n = 47). They were tested by enzyme immunoassay for anti-HEV IgM/IgG and real-time PCR for HEV RNA detection. The positive sample for HEV RNA was submitted for sequencing. The seroprevalence of anti-HEV IgM and IgG in group 1 was 4% (2/44) and 14.5% (7/44), respectively. Viral RNA was not detected in any sample. In group 2, the anti-HEV IgM positivity was 4.3% (2/47), and IgG 14.9% (7/47). RNA was detectable in one case, which presented a viral load of 222.4 IU/μL and positive anti-HEV IgM/IgG. In the phylogenetic analysis, the genotype identified was HEV-3f. These results indicate that HEV infection should be considered a possible diagnosis in cases of non-A-C AH. The patient identified with acute hepatitis E had recently traveled to the Northeast region of Brazil (Garanhuns city in Pernambuco state), where there are reports of high HEV seroprevalence among pigs. The close phylogenetic relationship observed between the sequence characterized in this study and strains isolated from pigs in nearby cities where the patient went suggested a possible zoonotic transmission in this region. This study highlights the importance of expanding studies and improving surveillance to understand better and manage HEV infections nationwide.
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Affiliation(s)
- Leidiane B Ribeiro
- Laboratório de Gastroenterologia e Hepatologia Tropical, LIM-07, Instituto de Medicina Tropical, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Luciana A Reche
- Laboratório de Gastroenterologia e Hepatologia Tropical, LIM-07, Instituto de Medicina Tropical, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Ana C de Seixas Santos Nastri
- Departamento de Doenças Infecciosas e Parasitárias, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | | | - Luciana V B Casadio
- Departamento de Doenças Infecciosas e Parasitárias, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Suzane K Ono
- Departamento de Gastroenterologia, Divisão de Gastroenterologia e Hepatologia Clinica, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Maria C Mendes-Correa
- Departamento de Doenças Infecciosas e Parasitárias, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
- Laboratório de Virologia, LIM-52, Instituto de Medicina Tropical, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Flair J Carrilho
- Departamento de Gastroenterologia, Divisão de Gastroenterologia e Hepatologia Clinica, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - João R R Pinho
- Laboratório de Gastroenterologia e Hepatologia Tropical, LIM-07, Instituto de Medicina Tropical, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
- Hospital Israelita Albert Einstein, Sao Paulo, Brazil
- Departamento de Gastroenterologia, Divisão de Gastroenterologia e Hepatologia Clinica, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Michele S Gomes-Gouvêa
- Laboratório de Gastroenterologia e Hepatologia Tropical, LIM-07, Instituto de Medicina Tropical, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
- Departamento de Gastroenterologia, Divisão de Gastroenterologia e Hepatologia Clinica, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
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6
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Yadav KK, Kenney SP. Hepatitis E virus immunosuppressed animal models. BMC Infect Dis 2024; 24:965. [PMID: 39266958 PMCID: PMC11395946 DOI: 10.1186/s12879-024-09870-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 09/03/2024] [Indexed: 09/14/2024] Open
Abstract
Hepatitis E virus (HEV) is an important emerging pathogen producing significant morbidity in immunosuppressed patients. HEV has been detrimental to solid organ transplant (SOT) patients, cancer patients, and HIV-positive patients, where chronic HEV infections occur. Blood-borne transfusions and multiple cases of chronic HEV infection in transplant patients have been reported in the past few decades, necessitating research on HEV pathogenesis using immunosuppressed animal models. Numerous animal species with unique naturally occurring HEV strains have been found, several of which have the potential to spread to humans and to serve as pathogenesis models. Host immunosuppression leads to viral persistence and chronic HEV infection allows for genetic adaptation to the human host creating new strains with worse disease outcomes. Procedures necessary for SOT often entail blood transfusions placing immunosuppressive patients into a "high risk group" for HEV infection. This scenario requires an appropriate immunosuppressive animal model to understand disease patterns in these patients. Hence, this article reviews the recent advances in the immunosuppressed animal models for chronic HEV infection with emphasis on pathogenesis, immune correlates, and the liver pathology associated with the chronic HEV infections.
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Affiliation(s)
- Kush Kumar Yadav
- Center for Food Animal Health, Department of Animal Sciences, The Ohio State University, 1680 Madison Ave, Wooster, OH, 44691, USA
- Department of Veterinary Preventive Medicine, The Ohio State University, Columbus, 43210, USA
| | - Scott P Kenney
- Center for Food Animal Health, Department of Animal Sciences, The Ohio State University, 1680 Madison Ave, Wooster, OH, 44691, USA.
- Department of Veterinary Preventive Medicine, The Ohio State University, Columbus, 43210, USA.
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7
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Quirino A, Marascio N, Branda F, Ciccozzi A, Romano C, Locci C, Azzena I, Pascale N, Pavia G, Matera G, Casu M, Sanna D, Giovanetti M, Ceccarelli G, Alaimo di Loro P, Ciccozzi M, Scarpa F, Maruotti A. Viral Hepatitis: Host Immune Interaction, Pathogenesis and New Therapeutic Strategies. Pathogens 2024; 13:766. [PMID: 39338957 PMCID: PMC11435051 DOI: 10.3390/pathogens13090766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Revised: 08/30/2024] [Accepted: 09/02/2024] [Indexed: 09/30/2024] Open
Abstract
Viral hepatitis is a major cause of liver illness worldwide. Despite advances in the understanding of these infections, the pathogenesis of hepatitis remains a complex process driven by intricate interactions between hepatitis viruses and host cells at the molecular level. This paper will examine in detail the dynamics of these host-pathogen interactions, highlighting the key mechanisms that regulate virus entry into the hepatocyte, their replication, evasion of immune responses, and induction of hepatocellular damage. The unique strategies employed by different hepatitis viruses, such as hepatitis B, C, D, and E viruses, to exploit metabolic and cell signaling pathways to their advantage will be discussed. At the same time, the innate and adaptive immune responses put in place by the host to counter viral infection will be analyzed. Special attention will be paid to genetic, epigenetic, and environmental factors that modulate individual susceptibility to different forms of viral hepatitis. In addition, this work will highlight the latest findings on the mechanisms of viral persistence leading to the chronic hepatitis state and the potential implications for the development of new therapeutic strategies. Fully understanding the complex host-pathogen interactions in viral hepatitis is crucial to identifying new therapeutic targets, developing more effective approaches for treatment, and shedding light on the mechanisms underlying progression to more advanced stages of liver damage.
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Affiliation(s)
- Angela Quirino
- Unit of Clinical Microbiology, Department of Health Sciences, “Magna Græcia” University of Catanzaro “Renato Dulbecco” Teaching Hospital, 88100 Catanzaro, Italy; (A.Q.); (N.M.); (G.P.); (G.M.)
| | - Nadia Marascio
- Unit of Clinical Microbiology, Department of Health Sciences, “Magna Græcia” University of Catanzaro “Renato Dulbecco” Teaching Hospital, 88100 Catanzaro, Italy; (A.Q.); (N.M.); (G.P.); (G.M.)
| | - Francesco Branda
- Unit of Medical Statistics and Molecular Epidemiology, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (C.R.); (M.C.)
| | - Alessandra Ciccozzi
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy; (A.C.); (C.L.); (D.S.); (F.S.)
| | - Chiara Romano
- Unit of Medical Statistics and Molecular Epidemiology, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (C.R.); (M.C.)
| | - Chiara Locci
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy; (A.C.); (C.L.); (D.S.); (F.S.)
- Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy; (I.A.); (N.P.); (M.C.)
| | - Ilenia Azzena
- Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy; (I.A.); (N.P.); (M.C.)
| | - Noemi Pascale
- Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy; (I.A.); (N.P.); (M.C.)
- Department of Chemical Physical Mathematical and Natural Sciences, University of Sassari, 07100 Sassari, Italy
| | - Grazia Pavia
- Unit of Clinical Microbiology, Department of Health Sciences, “Magna Græcia” University of Catanzaro “Renato Dulbecco” Teaching Hospital, 88100 Catanzaro, Italy; (A.Q.); (N.M.); (G.P.); (G.M.)
| | - Giovanni Matera
- Unit of Clinical Microbiology, Department of Health Sciences, “Magna Græcia” University of Catanzaro “Renato Dulbecco” Teaching Hospital, 88100 Catanzaro, Italy; (A.Q.); (N.M.); (G.P.); (G.M.)
| | - Marco Casu
- Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy; (I.A.); (N.P.); (M.C.)
| | - Daria Sanna
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy; (A.C.); (C.L.); (D.S.); (F.S.)
| | - Marta Giovanetti
- Department of Sciences and Technologies for Sustainable Development and One Health, Università Campus Bio-Medico di Roma, 00128 Rome, Italy;
- Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte 30190-002, MG, Brazil
- Climate Amplified Diseases and Epidemics (CLIMADE), Brasilia 70070-130, GO, Brazil
| | - Giancarlo Ceccarelli
- Department of Public Health and Infectious Diseases, University Hospital Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy;
| | | | - Massimo Ciccozzi
- Unit of Medical Statistics and Molecular Epidemiology, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (C.R.); (M.C.)
| | - Fabio Scarpa
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy; (A.C.); (C.L.); (D.S.); (F.S.)
| | - Antonello Maruotti
- Department GEPLI, Libera Università Maria Ss Assunta, 00193 Rome, Italy;
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8
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Memon MS, Kadir B, Kamani L, Chandio AA. Seroprevalence of Hepatitis-E Virus-Immunoglobulin G and its association with Chronic Liver Disease. Pak J Med Sci 2024; 40:1011-1016. [PMID: 38827844 PMCID: PMC11140340 DOI: 10.12669/pjms.40.5.8448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 01/22/2024] [Accepted: 02/18/2024] [Indexed: 06/05/2024] Open
Abstract
Background & Objective Viral hepatitis is a major public health concern in low-middle income countries. Hepatitis-E infection (HEV) is found globally but most prevalent in low-income countries especially those with poor sanitation systems, access to clean drinking water and health services. Superinfection with HEV in patients with chronic liver disease (CLD) can cause severe hepatic decompensation leading to increased morbidity and mortality. To determine the frequency of seroprevalence of Hepatitis-E virus Immunoglobulin g (IgG) and its association with chronic liver disease. Methods A cross-sectional study was conducted in Asian Institute of Medical Sciences, Hyderabad, Pakistan from January till May 2022. A total of 196 patients of aged ≥ 18 years, presenting in gastroenterology clinics were included in the study after informed consent. Result Among 196 patients, one third of patient were male (73.5%). Out of which 162 (82.7%) had liver disease and 34 (17.3%) were without liver disease. The median age of patient was 45 (33-51) years. The overall seroprevalence of HEV IgG among study population was 69.4%. HEV IgG was present in 114 and 22 in CLD and non CLD patients respectively. Multivariable regression shows no association between seroprevalence of HEV in CLD and non-CLD patient (AOR 1.02, 95% CI 0.45-2.313). Conclusion Our study showed high frequency of HEV seropositivity. No difference was observed in HEV seropositivity among CLD and non-CLD patients.
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Affiliation(s)
- Muhammad Sadik Memon
- Muhammad Sadik Memon, Professor, Asian Institute of Medical Sciences (AIMS) Hospital, Hyderabad, Pakistan
| | - Bushra Kadir
- Bushra Kadir, Consultant Gastroenterologist, Asian Institute of Medical Sciences (AIMS) Hospital, Hyderabad, Pakistan
| | - Lubna Kamani
- Lubna Kamani, Professor & Director GI Residency Program, Liaquat National Hospital, Karachi, Pakistan
| | - Ayaz Ahmed Chandio
- Ayaz Ahmed Chandio, Biostatician, Asian Institute of Medical Sciences (AIMS) Hospital, Hyderabad, Pakistan
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9
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Potemkin IA, Kyuregyan KK, Karlsen AA, Isaeva OV, Kichatova VS, Lopatukhina MA, Asadi Mobarkhan FA, Zlobina AG, Zheltobriukh AV, Bocharova KA, Belyakova VV, Rassolova SV, Ivanova NV, Solonin SA, Bazhenov AI, Godkov MA, Mikhailov MI. Hepatitis E Virus Infection in Voluntary Blood Donors in the Russian Federation. Viruses 2024; 16:526. [PMID: 38675869 PMCID: PMC11054373 DOI: 10.3390/v16040526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 03/26/2024] [Accepted: 03/27/2024] [Indexed: 04/28/2024] Open
Abstract
Transfusion-transmitted hepatitis E virus (HEV) infection is an increasing concern in many countries. We investigated the detection rate of HEV viremia in blood donors in Russia. A total of 20,405 regular repetitive voluntary non-renumerated blood donors from two regions (Moscow and Belgorod) were screened for HEV RNA using the cobas® HEV test in mini-pools of six plasma samples. Samples from each reactive pool were tested individually. The average HEV RNA prevalence was 0.024% (95% CI: 0.01-0.05%), or 1 case per 4081 donations. No statistically significant differences in HEV RNA prevalence were observed between the two study regions. The PCR threshold cycle (Ct) values ranged from 25.0 to 40.5 in reactive pools, and from 20.9 to 41.4 in reactive plasma samples when tested individually. The HEV viremic donors had different antibody patterns. Two donor samples were reactive for both anti-HEV IgM and IgG antibodies, one sample was reactive for anti-HEV IgM and negative for anti-HEV IgG, and two samples were seronegative. At follow-up testing 6 months later, on average, four donors available for follow-up had become negative for HEV RNA and positive for anti-HEV IgG. The HEV ORF2 sequence belonging to HEV-3 sub-genotype 3a was obtained from one donor sample. The sequencing failed in the other four samples from viremic donors, presumably due to the low viral load. In conclusion, the HEV RNA detection rate in blood donors in Russia corresponds with data from other European countries, including those that implemented universal donor HEV screening. These data support the implementation of HEV RNA donor screening to reduce the risk of transfusion-transmitted HEV infection in Russia.
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Affiliation(s)
- Ilya A. Potemkin
- Laboratory of Viral Hepatitis, Mechnikov Research Institute of Vaccines and Sera, 105064 Moscow, Russia; (I.A.P.); (A.A.K.); (O.V.I.); (V.S.K.); (M.A.L.); (F.A.A.M.); (M.I.M.)
- Laboratory of Molecular Epidemiology of Viral Hepatitis, Central Research Institute of Epidemiology, 111123 Moscow, Russia
| | - Karen K. Kyuregyan
- Laboratory of Viral Hepatitis, Mechnikov Research Institute of Vaccines and Sera, 105064 Moscow, Russia; (I.A.P.); (A.A.K.); (O.V.I.); (V.S.K.); (M.A.L.); (F.A.A.M.); (M.I.M.)
- Laboratory of Molecular Epidemiology of Viral Hepatitis, Central Research Institute of Epidemiology, 111123 Moscow, Russia
| | - Anastasia A. Karlsen
- Laboratory of Viral Hepatitis, Mechnikov Research Institute of Vaccines and Sera, 105064 Moscow, Russia; (I.A.P.); (A.A.K.); (O.V.I.); (V.S.K.); (M.A.L.); (F.A.A.M.); (M.I.M.)
- Laboratory of Molecular Epidemiology of Viral Hepatitis, Central Research Institute of Epidemiology, 111123 Moscow, Russia
| | - Olga V. Isaeva
- Laboratory of Viral Hepatitis, Mechnikov Research Institute of Vaccines and Sera, 105064 Moscow, Russia; (I.A.P.); (A.A.K.); (O.V.I.); (V.S.K.); (M.A.L.); (F.A.A.M.); (M.I.M.)
- Laboratory of Molecular Epidemiology of Viral Hepatitis, Central Research Institute of Epidemiology, 111123 Moscow, Russia
| | - Vera S. Kichatova
- Laboratory of Viral Hepatitis, Mechnikov Research Institute of Vaccines and Sera, 105064 Moscow, Russia; (I.A.P.); (A.A.K.); (O.V.I.); (V.S.K.); (M.A.L.); (F.A.A.M.); (M.I.M.)
- Laboratory of Molecular Epidemiology of Viral Hepatitis, Central Research Institute of Epidemiology, 111123 Moscow, Russia
| | - Maria A. Lopatukhina
- Laboratory of Viral Hepatitis, Mechnikov Research Institute of Vaccines and Sera, 105064 Moscow, Russia; (I.A.P.); (A.A.K.); (O.V.I.); (V.S.K.); (M.A.L.); (F.A.A.M.); (M.I.M.)
- Laboratory of Molecular Epidemiology of Viral Hepatitis, Central Research Institute of Epidemiology, 111123 Moscow, Russia
| | - Fedor A. Asadi Mobarkhan
- Laboratory of Viral Hepatitis, Mechnikov Research Institute of Vaccines and Sera, 105064 Moscow, Russia; (I.A.P.); (A.A.K.); (O.V.I.); (V.S.K.); (M.A.L.); (F.A.A.M.); (M.I.M.)
- Laboratory of Molecular Epidemiology of Viral Hepatitis, Central Research Institute of Epidemiology, 111123 Moscow, Russia
| | - Anna G. Zlobina
- Belgorod Blood Center, 308007 Belgorod, Russia; (A.G.Z.); (A.V.Z.)
| | | | - Ksenia A. Bocharova
- Medical Faculty, Belgorod State National Research University, 308015 Belgorod, Russia;
| | - Vera V. Belyakova
- Gavrilov Moscow Blood Center, Moscow Health Department, 125284 Moscow, Russia; (V.V.B.); (S.V.R.); (N.V.I.)
| | - Svetlana V. Rassolova
- Gavrilov Moscow Blood Center, Moscow Health Department, 125284 Moscow, Russia; (V.V.B.); (S.V.R.); (N.V.I.)
| | - Nadezhda V. Ivanova
- Gavrilov Moscow Blood Center, Moscow Health Department, 125284 Moscow, Russia; (V.V.B.); (S.V.R.); (N.V.I.)
| | - Sergey A. Solonin
- Sklifosovsky Research Institute for Emergency Medicine, Moscow Health Department, 129090 Moscow, Russia; (S.A.S.); (A.I.B.); (M.A.G.)
| | - Alexey I. Bazhenov
- Sklifosovsky Research Institute for Emergency Medicine, Moscow Health Department, 129090 Moscow, Russia; (S.A.S.); (A.I.B.); (M.A.G.)
| | - Mikhail A. Godkov
- Sklifosovsky Research Institute for Emergency Medicine, Moscow Health Department, 129090 Moscow, Russia; (S.A.S.); (A.I.B.); (M.A.G.)
| | - Mikhail I. Mikhailov
- Laboratory of Viral Hepatitis, Mechnikov Research Institute of Vaccines and Sera, 105064 Moscow, Russia; (I.A.P.); (A.A.K.); (O.V.I.); (V.S.K.); (M.A.L.); (F.A.A.M.); (M.I.M.)
- Laboratory of Molecular Epidemiology of Viral Hepatitis, Central Research Institute of Epidemiology, 111123 Moscow, Russia
- Medical Faculty, Belgorod State National Research University, 308015 Belgorod, Russia;
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10
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Martino C, Di Luca A, Bennato F, Ianni A, Passamonti F, Rampacci E, Henry M, Meleady P, Martino G. Label-Free Quantitative Analysis of Pig Liver Proteome after Hepatitis E Virus Infection. Viruses 2024; 16:408. [PMID: 38543773 PMCID: PMC10976091 DOI: 10.3390/v16030408] [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: 11/28/2023] [Revised: 03/01/2024] [Accepted: 03/04/2024] [Indexed: 05/23/2024] Open
Abstract
Hepatitis E represents an emerging zoonotic disease caused by the Hepatitis E virus (HEV), for which the main route of transmission is foodborne. In particular, infection in humans has been associated with the consumption of contaminated undercooked meat of pig origin. The aim of this study was to apply comparative proteomics to determine if porcine liver protein profiles could be used to distinguish between pigs seropositive and seronegative for HEV. Preliminarily, an ELISA was used to evaluate the presence of anti-HEV antibodies in the blood serum of 136 animals sent to slaughter. Among the analyzed samples, a seroprevalence of 72.8% was estimated, and it was also possible to identify 10 animals, 5 positive and 5 negative, coming from the same farm. This condition created the basis for the quantitative proteomics comparison between homogeneous animals, in which only the contact with HEV should represent the discriminating factor. The analysis of the proteome in all samples of liver exudate led to the identification of 554 proteins differentially expressed between the two experimental groups, with 293 proteins having greater abundance in positive samples and 261 more represented in negative exudates. The pathway enrichment analysis allowed us to highlight the effect of the interaction between HEV and the host biological system in inducing the potential enrichment of 69 pathways. Among these, carbon metabolism stands out with the involvement of 41 proteins, which were subjected to interactomic analysis. This approach allowed us to focus our attention on three enzymes involved in glycolysis: glucose-6-phosphate isomerase (GPI), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and fructose-bisphosphate aldolase A (ALDOA). It therefore appears that infection with HEV induced a strengthening of the process, which involves the breakdown of glucose to obtain energy and carbon residues useful for the virus's survival. In conclusion, the label-free LC-MS/MS approach showed effectiveness in highlighting the main differences induced on the porcine liver proteome by the interaction with HEV, providing crucial information in identifying a viral signature on the host metabolism.
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Affiliation(s)
- Camillo Martino
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy; (C.M.); (F.P.); (E.R.)
| | - Alessio Di Luca
- Department of BioScience and Technology for Food, Agriculture, and Environment, University of Teramo, 64100 Teramo, Italy; (A.D.L.); (F.B.); (G.M.)
| | - Francesca Bennato
- Department of BioScience and Technology for Food, Agriculture, and Environment, University of Teramo, 64100 Teramo, Italy; (A.D.L.); (F.B.); (G.M.)
| | - Andrea Ianni
- Department of BioScience and Technology for Food, Agriculture, and Environment, University of Teramo, 64100 Teramo, Italy; (A.D.L.); (F.B.); (G.M.)
| | - Fabrizio Passamonti
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy; (C.M.); (F.P.); (E.R.)
| | - Elisa Rampacci
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy; (C.M.); (F.P.); (E.R.)
| | - Michael Henry
- National Institute for Cellular Biotechnology, Dublin City University, D09 DX63 Dublin, Ireland; (M.H.); (P.M.)
| | - Paula Meleady
- National Institute for Cellular Biotechnology, Dublin City University, D09 DX63 Dublin, Ireland; (M.H.); (P.M.)
| | - Giuseppe Martino
- Department of BioScience and Technology for Food, Agriculture, and Environment, University of Teramo, 64100 Teramo, Italy; (A.D.L.); (F.B.); (G.M.)
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11
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Mohamed I, Sanders K, Hillebrand DJ. Chronic Hepatitis E Virus Manifesting as Elevated Transaminases in a Heart Transplant Patient. ACG Case Rep J 2024; 11:e01308. [PMID: 38524259 PMCID: PMC10959561 DOI: 10.14309/crj.0000000000001308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 02/22/2024] [Indexed: 03/26/2024] Open
Abstract
Hepatitis E virus (HEV) is a common cause of viral hepatitis worldwide. Genotypes 1 and 2 cause acute hepatitis in endemic regions (Asia and Africa), whereas genotypes 3 and 4 (America and Europe) result in sporadic acute or chronic hepatitis, specifically in certain groups. HEV infections are rising because of increased transplantation rates and immunosuppression. We report a 75-year-old heart transplant patient with nonspecific symptoms, diagnosed with HEV chronic hepatitis. Despite ribavirin-induced hemolytic anemia, the patient achieved sustained virological response and normalization of liver enzymes.
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Affiliation(s)
- Islam Mohamed
- Department of Internal Medicine, University of Missouri-Kansas City, Kansas City, MO
| | - Kimberly Sanders
- Department of Gastroenterology and Hepatology, University of Missouri-Kansas City, Kansas City, MO
| | - Donald J. Hillebrand
- Department of Gastroenterology and Hepatology, University of Kansas Health System, Kansas City, KS
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12
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Sant'Anna MB, Kimura LF, Vieira WF, Zambelli VO, Novaes LS, Hösch NG, Picolo G. Environmental factors and their impact on chronic pain development and maintenance. Phys Life Rev 2024; 48:176-197. [PMID: 38320380 DOI: 10.1016/j.plrev.2024.01.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 01/23/2024] [Indexed: 02/08/2024]
Abstract
It is more than recognized and accepted that the environment affects the physiological responses of all living things, from bacteria to superior vertebrates, constituting an important factor in the evolution of all species. Environmental influences range from natural processes such as sunlight, seasons of the year, and rest to complex processes like stress and other mood disorders, infections, and air pollution, being all of them influenced by how each creature deals with them. In this chapter, it will be discussed how some of the environmental elements affect directly or indirectly neuropathic pain, a type of chronic pain caused by a lesion or disease of the somatosensory nervous system. For that, it was considered the edge of knowledge in translational research, thus including data from human and experimental animals as well as the applicability of such findings.
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Affiliation(s)
| | - Louise Faggionato Kimura
- Laboratory of Pain and Signaling, Butantan Institute, São Paulo, Brazil; Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, USA
| | - Willians Fernando Vieira
- Laboratory of Functional Neuroanatomy of Pain, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil
| | | | - Leonardo Santana Novaes
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | | | - Gisele Picolo
- Laboratory of Pain and Signaling, Butantan Institute, São Paulo, Brazil.
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13
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Smatti MK, Al-Sarraj YA, Albagha O, Yassine HM. Genome-wide association study identifies several loci for HEV seropositivity. iScience 2023; 26:107586. [PMID: 37664632 PMCID: PMC10470371 DOI: 10.1016/j.isci.2023.107586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 06/22/2023] [Accepted: 08/04/2023] [Indexed: 09/05/2023] Open
Abstract
Hepatitis E viral (HEV) infection imposes a heavy global health burden. The variability in the prevalence of serological markers of HEV infection between different ethnic groups proposes a host genetic influence. Here, we report genetic polymorphisms associated with anti-HEV antibody positivity and level using binary- and quantitative-trait genome-wide association studies (GWAS) on a population from Qatar (n = 5829). We identified a region in 12p11.1 (lead SNP: rs559856097, allele: A, p = 2.3 × 10-10) significantly associated with anti-HEV antibodies level. This intergenic variant is located near SNORD112, a small nucleolar RNA (snoRNA). Additional gene-set and pathway enrichment analyses highlighted a strong correlation with anti-viral response-related pathways, including IFNs (alpha/beta) and interleukin-21 (IL-21) signaling. This is the first GWAS on the response to HEV infection. Further replication and functional experimentation are warranted to validate these findings.
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Affiliation(s)
- Maria K. Smatti
- College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
| | - Yasser A. Al-Sarraj
- College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
- Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar
| | - Omar Albagha
- College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
- Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK
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14
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Cao K, Wu X, Yang M, Chen C, Zhang X, Jiang D, Du Y, Chen M, You Y, Zhou W, Qi J, Chen D, Yan R, Miao Z, Yang S. Prevalence of hepatitis E virus in China from 1997 to 2022: a systematic review and meta-analysis. Front Public Health 2023; 11:1243408. [PMID: 37744517 PMCID: PMC10512461 DOI: 10.3389/fpubh.2023.1243408] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 08/22/2023] [Indexed: 09/26/2023] Open
Abstract
Introduction Several studies have reported on hepatitis E virus (HEV) prevalence in various regions of China, but the results vary widely. Herein, we conducted a systematic review and meta-analysis to assess the seroprevalence, RNA-positive rate, genotype distribution of HEV in China, and its risk factors. Methods We included 208 related studies involving 1,785,569 participants published between 1997 and 2022. Random-effects models were used to pool prevalence, and subgroup analyses were conducted by population, gender, age, study period, regions, and rural-urban distribution. The meta regression models and pooled odds ratios (OR) were performed to identify risk factors for HEV infections. Results The pooled anti-HEV IgG, IgM, and Ag seroprevalence, and RNA detection rates in China from 1997 to 2022 were 23.17% [95% confidence interval (CI): 20.23-26.25], 0.73% (95% CI: 0.55-0.93), 0.12% (95% CI: 0.01-0.32), and 6.55% (95% CI: 3.46-12.05), respectively. The anti-HEV IgG seropositivity was higher in the occupational population (48.41%; 95% CI: 40.02-56.85) and older adult aged 50-59 years (40.87%; 95% CI: 31.95-50.11). The dominant genotype (GT) of hepatitis E in China was GT4. Notably, drinking non-tap water (OR = 1.82; 95% CI: 1.50-2.20), consumption of raw or undercooked meat (OR = 1.47; 95% CI: 1.17-1.84), and ethnic minorities (OR = 1.50; 95% CI: 1.29-1.73) were risk factors of anti-HEV IgG seroprevalence. Discussions Overall, the prevalence of hepatitis E was relatively high in China, especially among older adults, ethnic minorities, and humans with occupational exposure to pigs. Thus, there is a need for preventive measures, including HEV infection screening and surveillance, health education, and hepatitis E vaccine intervention in high-risk areas and populations. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42023397036.
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Affiliation(s)
- Kexin Cao
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Public Health, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaoyue Wu
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Public Health, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Mengya Yang
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Public Health, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Can Chen
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Public Health, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaobao Zhang
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Public Health, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Daixi Jiang
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Public Health, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Yuxia Du
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Public Health, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Mengsha Chen
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Public Health, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Yue You
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Public Health, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Wenkai Zhou
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Public Health, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiaxing Qi
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Public Health, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Dingmo Chen
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Public Health, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Rui Yan
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - Ziping Miao
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - Shigui Yang
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Public Health, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
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15
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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.
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Affiliation(s)
- Mohammad Sultan Khuroo
- Digestive Diseases Centre, Dr. Khuroo's Medical Clinic, Srinagar, Jammu & Kashmir 190010, India
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Songtanin B, Molehin AJ, Brittan K, Manatsathit W, Nugent K. Hepatitis E Virus Infections: Epidemiology, Genetic Diversity, and Clinical Considerations. Viruses 2023; 15:1389. [PMID: 37376687 DOI: 10.3390/v15061389] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 06/13/2023] [Accepted: 06/15/2023] [Indexed: 06/29/2023] Open
Abstract
According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are four main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal-oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans via undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection, and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.
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Affiliation(s)
- Busara Songtanin
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Adebayo J Molehin
- Department of Microbiology & Immunology, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA
| | - Kevin Brittan
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Wuttiporn Manatsathit
- Department of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Kenneth Nugent
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
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Calibrating Hepatitis E Virus Serological Assays Using Asymptomatic Specimens Obtained in Japan. Microbiol Spectr 2022; 10:e0214622. [PMID: 36125314 PMCID: PMC9603090 DOI: 10.1128/spectrum.02146-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
This study aimed to calibrate hepatitis E virus (HEV) serological assays. We optimized the previously developed in-house HEV antibody enzyme-linked immunosorbent assay (ELISA) by setting the cutoff with an in-house serological performance panel consisting of broad HEV antibody titers and subtracting nonspecific background values for anti-HEV IgM, IgA, and IgG. We also compared the assay's performance with that of commercial serological assay kits (four kits for IgM, one for IgA, and two for IgG). Although all serological assays readily detected HEV antibodies at high titers in the symptomatic hepatitis E population, considerable variations between assays were observed in the asymptomatic population. The in-house ELISA showed a higher sensitivity for HEV IgM, IgA, and IgG than the commercial kits and detected the seroconversion of HEV IgM and IgG earlier when testing a commercially available HEV seroconversion panel. The low sensitivity of the commercial kits was due to the high setting of the original cutoff, which was demonstrated by receiver operating characteristic analysis. However, the corrected cutoff value reduced assay specificity. Background subtraction is essential to achieve high specificity because the in-house ELISA without background subtraction reduced its specificity. These results indicate that asymptomatic specimens and background subtraction contribute to the optimization of HEV serological assays. IMPORTANCE Accurate diagnosis of hepatitis E virus (HEV) infection is essential for public health surveillance and for preventing HEV-contaminated blood transfusion. Anti-HEV IgM or IgA is used as a reliable marker of recent HEV infection. However, considerable variability in the sensitivity and specificity of HEV antibody detection is observed among several commercially available assay kits. In addition, none of the HEV antibody detection methods have been approved by the U.S. Food and Drug Administration (FDA). Here, we show that the in-house enzyme-linked immunosorbent assay (ELISA) could detect HEV IgM and IgA more sensitively than commercial kits in the asymptomatic population. We also suggest that the assay performance of commercial kits might be improved by optimizing the cutoff and reducing nonspecific background noise. A sensitive serological (IgM or IgA) assay in addition to HEV RNA testing will contribute to accurate diagnosis of acute HEV infection because HEV RNA-positive duration is relatively short.
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Xiang Z, Jiang B, Li W, Zhai G, Zhou H, Wang Y, Wu J. The diagnostic and prognostic value of serum exosome-derived carbamoyl phosphate synthase 1 in HEV-related acute liver failure patients. J Med Virol 2022; 94:5015-5025. [PMID: 35760734 DOI: 10.1002/jmv.27961] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 06/13/2022] [Accepted: 06/14/2022] [Indexed: 11/06/2022]
Abstract
Early diagnosis and prognosis evaluation are of great significance to hepatitis E virus (HEV)-related acute liver failure (HEV-ALF) patients. We collected serum samples from 200 health controls (HCs), 200 patients with acute hepatitis E (AHE), and 200 HEV-ALF patients to evaluate serum exosome-derived carbamoyl phosphate synthase 1 (CPS1) levels and determine its diagnostic and prognostic value. The exosome-derived CPS1 levels in the HEV-ALF group were significantly higher than those in the AHE and HCs groups. The AUC of exosome-derived CPS1 to predict the occurrence of HEV-ALF was 0.850 (0.811-0.883). Both logistical regression and orthogonal partial least squares discriminant analysis (OPLS-DA) showed that exosome-derived CPS1 is an independent risk factor for HEV-ALF. The exosome-derived CPS1 levels were positively correlated with organ failure and the outcomes in HEV-ALF patients. The exosome-derived CPS1 levels in the worsening group were significantly higher than those in the fluctuating and the improving groups. The AUC of serum exosome-derived CPS1 to predict 30-day mortality was 0.829 (0.770-0.879), which was significantly greater than that of the Child-Pugh, KCH, and MELD models. The level of serum exosome-derived CPS1 might serve as a promising diagnostic and prognostic biomarker for HEV-ALF patients, which may provide better guidance for the diagnosis, prognosis, and treatment of HEV-ALF patients.
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Affiliation(s)
- Ze Xiang
- Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Bin Jiang
- Department of Laboratory Medicine, The Central Blood Station of Yancheng City, Yancheng, China
| | - Wei Li
- Department of Hepatology, The Second People's Hospital of Fuyang City, Fuyang, China
| | - Guanghua Zhai
- Department of Clinical Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China
| | - Hao Zhou
- Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ying Wang
- Department of Infection Management, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China
| | - Jian Wu
- Department of Clinical Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China
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Ahmad T, Jin H, Dhama K, Yatoo MI, Tiwari R, Bilal M, Dhawan M, Emran TB, Alestad JH, Alhani HM, BinKhalaf HK, Rabaan AA. Hepatitis E virus in pigs and the environment: An updated review of public health concerns. NARRA J 2022; 2:e78. [PMID: 38449702 PMCID: PMC10914032 DOI: 10.52225/narra.v2i2.78] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 07/22/2022] [Indexed: 09/01/2023]
Abstract
Hepatitis E virus (HEV) is an important public health problem and is responsible for both acute and chronic viral hepatitis. Public health implications of HEV are derived from its transmission route, either water-borne or food-borne, and its zoonotic potential. Not only in developing countries, but HEV cases are also found in a high number in developed countries. The spread of HEV to the environment might pollute surface waters, which could act as the source of infection for both humans and animals. Identification of the virus in animal products suggests the circulation of HEV within water and food chains. High seroprevalence and circulation of HEV in livestock, in particular pigs, as well as in environmental samples warrants further investigation into pig markets. HEV virulence in different environments and meat supply chains could shed light on the possible sources of infection in humans and the degree of occupational risk. The purpose of this review is to discuss HEV infections with an emphasis on livestock- and environment-related risk factors, and food-borne, water-borne, and zoonotic transmissions.
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Affiliation(s)
- Tauseef Ahmad
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing,Chinas
| | - Hui Jin
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing,Chinas
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
| | - Mohd. Iqbal Yatoo
- Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Srinagar, Jammu and Kashmir, Indias
| | - Ruchi Tiwari
- Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, Uttar Pradesh Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go Anusandhan Sansthan (DUVASU), Mathura, India
| | - Muhammad Bilal
- School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian, China
| | - Manish Dhawan
- Department of Microbiology, Punjab Agricultural University, Ludhiana, India
- The Trafford Group of Colleges, Manchester, United Kingdom
| | - Talha B. Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, Bangladesh
| | - Jeehan H. Alestad
- Immunology and Infectious Microbiology, Glasgow, United Kingdom
- Collage of medicine, Microbiology, Jabriya, Kuwait
- Kuwait Chair Madam in Antimicrobial Resistance Committee, Alternative Permanent Representative of Kuwait to the United Nation Agencies, Rome, Italys
| | - Hatem M. Alhani
- Department of Pediatric Infectious Disease, Maternity and Children Hospital, Dammam, Saudi Arabia
- Department of Infection Control, Maternity and Children Hospital, Dammam, Saudi Arabia
- Department of Preventive Medicine and Infection Prevention and Control, Directorate of Ministry of Health, Eastern Region, Dammam, Saudi Arabia
| | - Habib K. BinKhalaf
- Department of Molecular Laboratory, King Fahad Hospital, Hofuf, Saudi Arabia
| | - Ali A. Rabaan
- Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
- Department of Public Health and Nutrition, The University of Haripur, Haripur, Pakistan
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Farshadpour F, Taherkhani R, Shaeri M. Prevalence and risk factors of hepatitis E virus infection among patients with β-thalassemia major in South of Iran. J Immunoassay Immunochem 2022; 43:452-462. [PMID: 35230202 DOI: 10.1080/15321819.2022.2046602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
This study was performed to determine the prevalence and risk factors of hepatitis E virus (HEV) infection among thalassemia patients. All β-thalassemia major patients on regular blood transfusion attending the blood transfusion centers located in southern Iran were invited to participate in this study. ELISA was used to detect anti-HEV IgM and anti-HEV IgG antibodies. The molecular detection of HEV infection was performed by nested RT-PCR assay, targeting the ORF2 region of HEV genome, and sequencing. In this study, 16.67% of thalassemia patients were positive for anti-HEV IgG compared to 12.1% of the controls. Thalassemia patients were negative for anti-HEV IgM and HEV viremia. Patients with blood transfusion every two weeks had significantly higher anti-HEV IgG seroprevalence compared to the patients with blood transfusions at longer intervals (OR: 12.50; 95% CI: 1.76-88.74; P = .012). Anti-HEV IgG seroprevalence was not statistically associated with age, gender distribution, ethnicity, place of residency, education level, and serum levels of liver enzymes. This study reports a high seroprevalence of HEV among thalassemia patients, while frequency of blood transfusion was significantly associated with anti-HEV IgG seropositivity. This suggests that frequent blood transfusion may be a risk factor for exposure to HEV infection among thalassemia patients.
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Affiliation(s)
- Fatemeh Farshadpour
- Department of Virology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Reza Taherkhani
- Department of Virology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Marziyeh Shaeri
- Department of Virology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
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Li M, Wang Y, Li K, Lan H, Zhou C. Characterization of highly expressed novel hub genes in hepatitis E virus chronicity in rabbits: a bioinformatics and experimental analysis. BMC Vet Res 2022; 18:239. [PMID: 35739587 PMCID: PMC9219159 DOI: 10.1186/s12917-022-03337-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 06/06/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Hepatitis E virus (HEV), which is the leading cause of acute viral hepatitis worldwide, usually causes self-limited infections in common individuals. However, it can lead to chronic infection in immunocompromised individuals and its mechanisms remain unclear. Rabbits are the natural host of HEV, and chronic HEV infections have been observed in rabbits. Therefore, we aimed to investigate potential key genes in HEV chronicity process in rabbits. In this study, both bioinformatics and experimental analysis were performed to deepen the understanding of hub genes in HEV chronic infection in rabbits. RESULTS Ninety-four candidate differentially expressed genes (DEGs) and the pathways they enriched were identified to be related with HEV chronicity. A total of 10 hub genes were found by protein-protein interaction (PPI) network construction. Rabbits of group P (n = 4) which showed symptoms of chronic HEV infection were selected to be compared with HEV negative rabbits (group N, n = 6). By detecting the identified hub genes in groups P and N by real-time PCR, we found that the expressions of MX1, OAS2 and IFI44 were significantly higher in group P (P < 0.05). CONCLUSIONS In this work, we presented that MX1, OAS2 and IFI44 were significantly upregulated in HEV chronic infected rabbits, indicating that they may be involved in the pathogenesis of HEV chronicity.
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Affiliation(s)
- Manyu Li
- Division I of In Vitro Diagnostics for Infectious Diseases, Institute for In Vitro Diagnostics Control, National Institutes for Food and Drug Control, 2 Tiantanxili Rd, Dongcheng District, 100050, Beijing, China.
| | - Yan Wang
- First Clinical Medical College, Shanxi Medical University, Taiyuan, China
| | - Kejian Li
- Division I of In Vitro Diagnostics for Infectious Diseases, Institute for In Vitro Diagnostics Control, National Institutes for Food and Drug Control, 2 Tiantanxili Rd, Dongcheng District, 100050, Beijing, China
| | - Haiyun Lan
- Division I of In Vitro Diagnostics for Infectious Diseases, Institute for In Vitro Diagnostics Control, National Institutes for Food and Drug Control, 2 Tiantanxili Rd, Dongcheng District, 100050, Beijing, China
| | - Cheng Zhou
- Division I of In Vitro Diagnostics for Infectious Diseases, Institute for In Vitro Diagnostics Control, National Institutes for Food and Drug Control, 2 Tiantanxili Rd, Dongcheng District, 100050, Beijing, China.
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Marascio N, Rotundo S, Quirino A, Matera G, Liberto MC, Costa C, Russo A, Trecarichi EM, Torti C. Similarities, differences, and possible interactions between hepatitis E and hepatitis C viruses: Relevance for research and clinical practice. World J Gastroenterol 2022; 28:1226-1238. [PMID: 35431515 PMCID: PMC8968488 DOI: 10.3748/wjg.v28.i12.1226] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 01/06/2022] [Accepted: 02/23/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) and hepatitis C virus (HCV) are both RNA viruses with a tropism for liver parenchyma but are also capable of extrahepatic manifestations. Hepatitis E is usually a viral acute fecal-oral transmitted and self-limiting disease presenting with malaise, jaundice, nausea and vomiting. Rarely, HEV causes a chronic infection in immunocompromised persons and severe fulminant hepatitis in pregnant women. Parenteral HCV infection is typically asymptomatic for decades until chronic complications, such as cirrhosis and cancer, occur. Despite being two very different viruses in terms of phylogenetic and clinical presentations, HEV and HCV show many similarities regarding possible transmission through organ transplantation and blood transfusion, pathogenesis (production of antinuclear antibodies and cryoglobulins) and response to treatment with some direct-acting antiviral drugs. Although both HEV and HCV are well studied individually, there is a lack of knowledge about coinfection and its consequences. The aim of this review is to analyze current literature by evaluating original articles and case reports and to hypothesize some interactions that can be useful for research and clinical practice.
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Affiliation(s)
- Nadia Marascio
- Department of Health Sciences, Unit of Microbiology, University “Magna Graecia” of Catanzaro, Catanzaro 88100, Italy
| | - Salvatore Rotundo
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
| | - Angela Quirino
- Department of Health Sciences, Unit of Microbiology, University “Magna Graecia” of Catanzaro, Catanzaro 88100, Italy
| | - Giovanni Matera
- Department of Health Sciences, Unit of Microbiology, University “Magna Graecia” of Catanzaro, Catanzaro 88100, Italy
| | - Maria Carla Liberto
- Department of Health Sciences, Unit of Microbiology, University “Magna Graecia” of Catanzaro, Catanzaro 88100, Italy
| | - Chiara Costa
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
| | - Alessandro Russo
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
| | - Enrico Maria Trecarichi
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
| | - Carlo Torti
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
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Wu JY, Lau EH, Lu ML, Guo C, Guo ZM, Yuan J, Lu JH. An occupational risk of hepatitis E virus infection in the workers along the meat supply chains in Guangzhou, China. One Health 2022; 14:100376. [PMID: 35252529 PMCID: PMC8891999 DOI: 10.1016/j.onehlt.2022.100376] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 02/19/2022] [Accepted: 02/19/2022] [Indexed: 02/07/2023] Open
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NLRP3 Inflammasome Activation is a Prognostic Marker of Recovery in HEV-Infected Patients. Curr Microbiol 2022; 79:44. [PMID: 34982235 DOI: 10.1007/s00284-021-02736-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 12/02/2021] [Indexed: 12/31/2022]
Abstract
Hepatitis E contributes to 3.3 million acute hepatitis cases worldwide with 30% mortality in pregnant women. Pathogenesis of Hepatitis E is complex; thus, the present study was aimed at inflammasomes and associated cytokines in the immunopathogenesis of viral hepatitis E. PBMCs were isolated from 45 HEV IgM/HEV RNA-positive AVH/ALF and 19 healthy individuals and processed for mRNA expressions of NLRs, RLRs, and cytokines. PBMCs were cultured and stimulated with HEV-pORF-2 peptide in vitro for mRNA expression by RT-PCR and cytokines levels in serum/culture supernatant by ELISA. siRNA transfection and post-silencing effect in AVH PBMCs were also assessed by NLRP3 gene expression and IL-1β and IL-18 levels by ELISA. The results demonstrated high viral load in ALF than AVH cases. mRNA expression of NLRP3 in AVH patients was found to be positively correlated with IL-18 (r = 0.74) and IL-1β (r = 0.68); P < 0.0001***. Significant levels of serum IL-1β and IL-18 cytokines were observed in AVH as compared to ALF patients. The levels of IL-1β in the culture supernatant in mock and stimulated conditions were significantly higher in AVH than in ALF patients. Significant downregulation in NLRP3 gene expression was correlated with the reduced levels of IL-1β and IL-18 cytokines in NLRP3-siRNA-transfected PBMCs. This study highlighted the significance of upregulated NLRP3 inflammasome leading to increased production of IL-18 and IL-1β cytokines in sera of AVH patients. Thus, it indicated the role of Th1 response acting through the NLRP3 pathway which might have been helpful in the recovery of AVH patients. These promising results open multiple treatment avenues where specific inhibitors can be designed to modulate the progress of disease and its pathogenicity.
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Golkocheva-Markova E, Kevorkyan A, Raycheva R, Ismailova C, Yoncheva V, Tenev T, Emilova R, Grigorova L, Baltadzhiev I, Komitova R. Assessment of hepatitis E seropositivity among HIV-infected patients in Bulgaria. Braz J Infect Dis 2022; 26:102329. [PMID: 35176255 PMCID: PMC9387478 DOI: 10.1016/j.bjid.2022.102329] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 11/26/2021] [Accepted: 01/03/2022] [Indexed: 11/30/2022] Open
Abstract
It is debatable whether HIV-infected patients are at greater risk for hepatitis E virus (HEV) infection compared with healthy subjects. The reported anti-HEV seroprevalence among different groups in Bulgaria varied from 9.04% to 25.9%, but the information regarding the HIV population is still missing. The aim of the present study was to evaluate hepatitis E seroprevalence among HIV-infected patients in Bulgaria and to analyze demographic and immunological factors associated with HEV infection. Serum samples of 312 HIV-infected patients were analyzed retrospectively. Age, sex, residence and laboratory markers for HEV, HBV, HCV and HIV infection, and lymphocytes subpopulations were collected for all patients. None of the tested samples were positive for HEV RNA. HEV seroprevalence among HIV-infected patients was 10.9%. Males were more affected with the highest prevalence of positivity in the age group > 30 to ≤ 40 years. The documented HIV transmission routes in HIV/HEV co-infected group were heterosexual, homosexual, intravenous drug use (IDU), and vertical with predominace of the heterosexual route (z = 0.2; p = 0.804). There was a statistically significant trend of HIV mixed infection with routes of HIV transmission other than homosexual - heterosexual in HIV/HEV group and injection drug use in HIV/HBV/HCV co-infected group. The route of HIV transmission, in contexts of patients’ behavior, was associated with HEV prevalence among HIV-infected patients.
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Klöhn M, Schrader JA, Brüggemann Y, Todt D, Steinmann E. Beyond the Usual Suspects: Hepatitis E Virus and Its Implications in Hepatocellular Carcinoma. Cancers (Basel) 2021; 13:5867. [PMID: 34831021 PMCID: PMC8616277 DOI: 10.3390/cancers13225867] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/16/2021] [Accepted: 11/19/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus infections are the leading cause of viral hepatitis in humans, contributing to an estimated 3.3 million symptomatic cases and almost 44,000 deaths annually. Recently, HEV infections have been found to result in chronic liver infection and cirrhosis in severely immunocompromised patients, suggesting the possibility of HEV-induced hepatocarcinogenesis. While HEV-associated formation of HCC has rarely been reported, the expansion of HEV's clinical spectrum and the increasing evidence of chronic HEV infections raise questions about the connection between HEV and HCC. The present review summarizes current clinical evidence of the relationship between HEV and HCC and discusses mechanisms of virus-induced HCC development with regard to HEV pathogenesis. We further elucidate why the development of HEV-induced hepatocellular carcinoma has so rarely been observed and provide an outlook on possible experimental set-ups to study the relationship between HEV and HCC formation.
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Affiliation(s)
- Mara Klöhn
- Department of Molecular and Medical Virology, Ruhr-Universität Bochum, 44801 Bochum, Germany; (M.K.); (J.A.S.); (Y.B.); (D.T.)
| | - Jil Alexandra Schrader
- Department of Molecular and Medical Virology, Ruhr-Universität Bochum, 44801 Bochum, Germany; (M.K.); (J.A.S.); (Y.B.); (D.T.)
| | - Yannick Brüggemann
- Department of Molecular and Medical Virology, Ruhr-Universität Bochum, 44801 Bochum, Germany; (M.K.); (J.A.S.); (Y.B.); (D.T.)
| | - Daniel Todt
- Department of Molecular and Medical Virology, Ruhr-Universität Bochum, 44801 Bochum, Germany; (M.K.); (J.A.S.); (Y.B.); (D.T.)
- European Virus Bioinformatics Center (EVBC), 07743 Jena, Germany
| | - Eike Steinmann
- Department of Molecular and Medical Virology, Ruhr-Universität Bochum, 44801 Bochum, Germany; (M.K.); (J.A.S.); (Y.B.); (D.T.)
- German Centre for Infection Research (DZIF), External Partner Site, 44801 Bochum, Germany
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Kamani L, Padhani ZA, Das JK. Hepatitis E: Genotypes, strategies to prevent and manage, and the existing knowledge gaps. JGH Open 2021; 5:1127-1134. [PMID: 34621997 PMCID: PMC8485408 DOI: 10.1002/jgh3.12646] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 08/02/2021] [Accepted: 08/14/2021] [Indexed: 12/23/2022]
Abstract
Hepatitis E virus (HEV) is considered an emergent source of viral hepatitis worldwide, with an increasing burden of jaundice, liver failure, extrahepatic illnesses, and deaths in developed countries. With the scarcity of data from efficient animal models, there are still open-ended questions about designing new models to study pathogenesis, types, virology, and evolution of these viruses. With an emphasis on available data and updates, there is still enough information to understand the HEV life cycle, pathogen interaction with the host, and the valuation of the role of vaccine and new anti-HEV therapies. However, the World Health Organization (WHO) and the European Association for the Study of the Liver (EASL) preferred to stress prevention and control measures of HEV infections in animals, zoonotic transmission, and foodborne transmission. It is being reviewed that with current knowledge on HEV and existing prevention tools, there is an excellent room for in-depth information about the virus strains, their replication, pathogenicity, and virulence. The current knowledge set also has gaps regarding standardized and validated diagnostic tools, efficacy and safety of the vaccine, and extrahepatic manifestations specifically in pregnant females, immunocompromised patients, and others. This review highlights the areas for more research exploration, focusing on enlisted research questions based on HEV infection to endorse the need for significant improvement in the current set of knowledge for this public health problem.
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Affiliation(s)
- Lubna Kamani
- Associate Professor & Director, GI Residency Program, Department of GastroenterologyLiaquat National Hospital and Medical CollegeKarachiPakistan
- ConsultantAga Khan University HospitalKarachiPakistan
| | - Zahra Ali Padhani
- Health Policy and Management, Manager (Research)Aga Khan University HospitalKarachiPakistan
| | - Jai K Das
- Assistant Professor and Head, Section of Public Health and EpidemiologyAga Khan University HospitalKarachiPakistan
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Interplay between Hepatitis E Virus and Host Cell Pattern Recognition Receptors. Int J Mol Sci 2021; 22:ijms22179259. [PMID: 34502167 PMCID: PMC8431321 DOI: 10.3390/ijms22179259] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Revised: 08/02/2021] [Accepted: 08/06/2021] [Indexed: 11/23/2022] Open
Abstract
Hepatitis E virus (HEV) usually causes self-limiting acute hepatitis, but the disease can become chronic in immunocompromised individuals. HEV infection in pregnant women is reported to cause up to 30% mortality, especially in the third trimester. Additionally, extrahepatic manifestations like neuronal and renal diseases and pancreatitis are also reported during the course of HEV infection. The mechanism of HEV pathogenesis remains poorly understood. Innate immunity is the first line of defense triggered within minutes to hours after the first pathogenic insult. Growing evidence based on reverse genetics systems, in vitro cell culture models, and representative studies in animal models including non-human primates, has implicated the role of the host’s innate immune response during HEV infection. HEV persists in presence of interferons (IFNs) plausibly by evading cellular antiviral defense. This review summarizes our current understanding of recognizing HEV-associated molecular patterns by host cell Pattern Recognition Receptors (PRRs) in eliciting innate immune response during HEV infection as well as mechanisms of virus-mediated immune evasion.
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Torre P, Aglitti A, Masarone M, Persico M. Viral hepatitis: Milestones, unresolved issues, and future goals. World J Gastroenterol 2021; 27:4603-4638. [PMID: 34366625 PMCID: PMC8326259 DOI: 10.3748/wjg.v27.i28.4603] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 04/11/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
In this review the current overall knowledge on hepatitis A, B, C, D, and E will be discussed. These diseases are all characterized by liver inflammation but have significant differences in distribution, transmission routes, and outcomes. Hepatitis B virus and hepatitis C virus are transmitted by exposure to infected blood, and in addition to acute infection, they can cause chronic hepatitis, which in turn can evolve into cirrhosis. It is estimated that more than 300 million people suffer from chronic hepatitis B or C worldwide. Hepatitis D virus, which is also transmitted by blood, only affects hepatitis B virus infected people, and this dual infection results in worse liver-related outcomes. Hepatitis A and E spread via the fecal-oral route, which corresponds mainly to the ingestion of food or water contaminated with infected stools. However, in developed countries hepatitis E is predominantly a zoonosis. Although hepatitis A virus and hepatitis E virus are usually responsible for a self-limiting hepatitis, a serious, rarely fatal illness is also possible, and in immunosuppressed patients, such as organ transplant recipients, hepatitis E virus infection can become chronic. The description of goals achieved, unresolved issues, and the latest research on this topic may make it possible to speculate on future scenarios in the world of viral hepatitis.
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Affiliation(s)
- Pietro Torre
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
| | - Andrea Aglitti
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
| | - Mario Masarone
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
| | - Marcello Persico
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
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Mechanism of Cross-Species Transmission, Adaptive Evolution and Pathogenesis of Hepatitis E Virus. Viruses 2021; 13:v13050909. [PMID: 34069006 PMCID: PMC8157021 DOI: 10.3390/v13050909] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 05/12/2021] [Accepted: 05/13/2021] [Indexed: 12/17/2022] Open
Abstract
Hepatitis E virus (HEV) is the leading cause of acute hepatitis worldwide. While the transmission in developing countries is dominated by fecal-oral route via drinking contaminated water, the zoonotic transmission is the major route of HEV infection in industrialized countries. The discovery of new HEV strains in a growing number of animal species poses a risk to zoonotic infection. However, the exact mechanism and the determinant factors of zoonotic infection are not completely understood. This review will discuss the current knowledge on the mechanism of cross-species transmission of HEV infection, including viral determinants, such as the open reading frames (ORFs), codon usage and adaptive evolution, as well as host determinants, such as host cellular factors and the host immune status, which possibly play pivotal roles during this event. The pathogenesis of hepatitis E infection will be briefly discussed, including the special forms of this disease, including extrahepatic manifestations, chronic infection, and fulminant hepatitis in pregnant women.
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Fagan O, Amstrong P, Merwe KVD, Crosnoi D, Steele C, Sopena-Falco J, Parihar V. Viral hepatitis: A brief introduction, review of management, advances and challenges. World J Meta-Anal 2021; 9:139-151. [DOI: 10.13105/wjma.v9.i2.139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/26/2021] [Accepted: 04/23/2021] [Indexed: 02/06/2023] Open
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Talapko J, Meštrović T, Pustijanac E, Škrlec I. Towards the Improved Accuracy of Hepatitis E Diagnosis in Vulnerable and Target Groups: A Global Perspective on the Current State of Knowledge and the Implications for Practice. Healthcare (Basel) 2021; 9:133. [PMID: 33572764 PMCID: PMC7912707 DOI: 10.3390/healthcare9020133] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/21/2021] [Accepted: 01/26/2021] [Indexed: 02/07/2023] Open
Abstract
The hepatitis E virus (HEV) is a positive single-stranded, icosahedral, quasi-enveloped RNA virus in the genus Orthohepevirus of the family Hepeviridae. Orthohepevirus A is the most numerous species of the genus Orthohepevirus and consists of eight different HEV genotypes that can cause infection in humans. HEV is a pathogen transmitted via the fecal-oral route, most commonly by consuming fecally contaminated water. A particular danger is the HEV-1 genotype, which poses a very high risk of vertical transmission from the mother to the fetus. Several outbreaks caused by this genotype have been reported, resulting in many premature births, abortions, and also neonatal and maternal deaths. Genotype 3 is more prevalent in Europe; however, due to the openness of the market, i.e., trade-in animals which represent a natural reservoir of HEV (such as pigs), there is a possibility of spreading HEV infections outside endemic areas. This problem is indeed global and requires increased hygiene measures in endemic areas, which entails special care for pregnant women in both endemic and non-endemic regions. As already highlighted, pregnant women could have significant health consequences due to the untimely diagnosis of HEV infection; hence, this is a population that should be targeted with a specific combination of testing approaches to ensure optimal specificity and sensitivity. Until we advance from predominantly supportive treatment in pregnancy and appraise the safety and efficacy of a HEV vaccine in this population, such screening approaches represent the mainstay of our public health endeavors.
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Affiliation(s)
- Jasminka Talapko
- Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, HR-31000 Osijek, Croatia;
| | - Tomislav Meštrović
- University Centre Varaždin, University North, HR-42000 Varaždin, Croatia;
- Clinical Microbiology and Parasitology Unit, Dr. Zora Profozić Polyclinic, HR-10000 Zagreb, Croatia
| | - Emina Pustijanac
- Faculty of Natural Sciences, Juraj Dobrila University of Pula, HR-52100 Pula, Croatia;
| | - Ivana Škrlec
- Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, HR-31000 Osijek, Croatia;
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