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Daniel R, Zelber-Sagi S, Barak M, Zuckerman E. The Epidemiology of Hepatitis E in Israel and Potential Risk Factors: A Cross-Sectional Population-Based Serological Survey of Hepatitis E Virus in Northern Israel. Viruses 2025; 17:536. [PMID: 40284979 PMCID: PMC12031424 DOI: 10.3390/v17040536] [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: 02/23/2025] [Revised: 04/01/2025] [Accepted: 04/03/2025] [Indexed: 04/29/2025] Open
Abstract
Hepatitis E Virus (HEV) has gained public health attention as one of the causative agents of viral hepatitis. Our study aimed to provide data about HEV seropositivity in the Israeli general population, including its seroprevalence geographical distribution, and to identify variables as possible risk factors for HEV exposure. A seroprevalence cross-sectional study was conducted: HEV serological status was determined in 716 blood samples collected from the routine check-up blood samples. Demographic information was available for all samples. The overall prevalence of HEV IgG in an apparently healthy population in the north of Israel was 10.5%, with no evidence of positive HEV IgM. There was a significant association between HEV seropositivity and elderly age and low socioeconomic status (SES). The age-adjusted seroprevalence was significantly lower among Jews compared to Arabs with a rate ratio of 2.02. We identified clusters (hot spots) of HEV infection in three regions under study. Our results confirmed a high prevalence of anti-HEV in the country where clinical hepatitis E is not endemic. For the first time, this study showed that a hot spot analysis was able to provide new knowledge about actual exposure zones. As HEV infection is not a notifiable disease, it is probably underdiagnosed. Thus, better awareness among physicians is warranted.
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Affiliation(s)
- Rasha Daniel
- Haifa and Western Galilee Central Laboratories, Clalit Health Services, Nesher 20300, Israel
| | - Shira Zelber-Sagi
- School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa 3498838, Israel;
| | - Mira Barak
- Head of Medical Laboratory Sciences, Zefat Academic College, Safed 13206, Israel;
| | - Eli Zuckerman
- Liver Unit, Carmel Medical Center, Faculty of Medicine, Technion Institute, Haifa 3498838, Israel
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Liu X, Liu T, Shao Z, Xiong X, Qi S, Guan J, Wang M, Tang YD, Feng Z, Wang L, Yin X. Palmitoylation-dependent association with Annexin II directs hepatitis E virus ORF3 sorting into vesicles and quasi-enveloped virions. Proc Natl Acad Sci U S A 2025; 122:e2418751122. [PMID: 39793027 PMCID: PMC11725905 DOI: 10.1073/pnas.2418751122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 11/25/2024] [Indexed: 01/12/2025] Open
Abstract
Historically considered to be nonenveloped, hepatitis E virus (HEV), an important zoonotic pathogen, has recently been discovered to egress from infected cells as quasi-enveloped virions. These quasi-enveloped virions circulating in the blood are resistant to neutralizing antibodies, thereby facilitating the stealthy spread of infection. Despite abundant evidence of the essential role of the HEV-encoded ORF3 protein in quasi-enveloped virus formation, the underlying mechanism remains unclear. Here, we demonstrate that the HEV ORF3 protein possesses an inherent capacity for self-secretion and that palmitoylation at two cysteine residues within the ORF3 N-terminal region is essential for its secretion and quasi-enveloped virus formation. We further found that only palmitoylated ORF3 proteins hijacked Annexin II for transport to the cytoskeleton and are then directed into multivesicular bodies through the nSMase-endosomal sorting complexes required for transport-III pathway for secretion. Finally, we show that infection of gerbils with HEV mutants harboring mutations at palmitoylation sites within ORF3 showed no fecal viral shedding but competent replication in the liver. Our study fills a gap in the understanding of the assembly and release of quasi-enveloped virions mediated by ORF3 and offers the potential for designing therapeutic strategies to control HEV infection.
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Affiliation(s)
- Xing Liu
- Division of Livestock Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin150069, China
| | - Tianxu Liu
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing100191, China
| | - Zhen Shao
- Division of Livestock Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin150069, China
| | - Xiaoyan Xiong
- Division of Livestock Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin150069, China
- Department of Animal Sciences, Quantitative Veterinary Epidemiology Group, Wageningen University, Wageningen6700 AH, The Netherlands
| | - Shuhui Qi
- Division of Livestock Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin150069, China
| | - Junyong Guan
- Division of Livestock Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin150069, China
| | - Menghang Wang
- Division of Livestock Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin150069, China
| | - Yan-Dong Tang
- Division of Livestock Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin150069, China
| | - Zongdi Feng
- Center for Vaccines and Immunity, The Research Institute at Nationwide Children’s Hospital, Columbus, OH43205
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH43205
| | - Lin Wang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing100191, China
| | - Xin Yin
- Division of Livestock Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin150069, China
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Fan Z, Xu L, Cao Y, Liu T, Tian Y, Pan Z, Mo Y, Wang X, Zhu X, Gao Y, Zhang X, Pan CQ, Wang L, Ren F. One-Pot Assay Based on CRISPR/Cas13a Technology for HEV RNA Point-of-Care Testing. J Med Virol 2024; 96:e70115. [PMID: 39704190 DOI: 10.1002/jmv.70115] [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: 07/16/2024] [Revised: 11/10/2024] [Accepted: 11/26/2024] [Indexed: 12/21/2024]
Abstract
Hepatitis E virus (HEV) poses a serious threat to both public health and animal food safety, thereby highlighting the demands for rapid, sensitive, and easy-to-use detection. This study aimed to develop a One-Pot assay using CRISPR/Cas13a for detecting HEV RNA, suitable for point-of-care testing (POCT) in resource-limited settings. CRISPR/Cas13a combined with reverse transcription polymerase chain reaction (RT-PCR) and reverse transcription recombinase-aided amplification (RT-RAA) was applied to a One-Pot assay device. Additionally, a large cohort of HEV-infected patient (154) and animal (104) specimens was utilized for validation. The RT-PCR/RT-RAA + CRISPR/Cas13a assays for HEV RNA detection (genotypes: HEV-1, HEV-3, and HEV-4) were established, optimized, and validated, achieving a limit of detection (LoD) of 1 copy/μL and 100% specificity. In the application validation for HEV infection, the positive rates of the RT-PCR + CRISPR and RT-RAA + CRISPR assays were 98.6% and 89.6% for patients, and 96.6% and 88.8% for animals, respectively, which were superior to those of RT-qPCR. Furthermore, sample rapid lysis, reagent lyophilization, and the One-Pot device were integrated to construct a One-Pot assay with an LoD of 102 copies/μL. Despite slight decreases in sensitivity, the One-Pot assay significantly reduces the assay time to 35 min, making it easy to perform, minimizing contamination, and meeting the requirements for screening. We developed a One-Pot assay of HEV RNA using the CRISPR/Cas13a which effectively realizes a POCT test and maximizes the impetus for POCT implementation and shows potential as a valuable tool for detecting and monitoring HEV infection.
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Grants
- This study was supported by the National Natural Science Foundation of China (82002243, 82100653), Key Projects of the Beijing Municipal Education Commission's Science and Technology Plan (KZ202010025035), Chinese Institutes for Medical Research, Beijing (Grant No. CX24PY23), Beijing Hospitals Authority Youth Programme (QML20201702), Talent Cultivation Plan of Climbing the Peak of Beijing Municipal Hospital Administration (DFL20221503), Beijing Natural Science Foundation-Changping Innovation Joint Fund (L234046), Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University (CCMU2023ZKYXZ003), High-Level Public Health Technical Talents Project of Beijing (Subject Leaders-02-13, xuekegugan-03-48).
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Affiliation(s)
- Zihao Fan
- Beijing Institute of Hepatology/Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Ling Xu
- Beijing Institute of Hepatology/Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Yaling Cao
- Beijing Institute of Hepatology/Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Tianxu Liu
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Yuan Tian
- Beijing Institute of Hepatology/Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Zhenzhen Pan
- Beijing Institute of Hepatology/Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Yinkang Mo
- Beijing Institute of Hepatology/Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Xinyu Wang
- Beijing Institute of Hepatology/Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Xianru Zhu
- Beijing Institute of Hepatology/Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Yao Gao
- Beijing Institute of Hepatology/Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Xiangying Zhang
- Beijing Institute of Hepatology/Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Calvin Q Pan
- NYU Langone Medical Center, New York University School of Medicine, New York City, New York, USA
| | - Lin Wang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Feng Ren
- Beijing Institute of Hepatology/Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
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Letafati A, Taghiabadi Z, Roushanzamir M, Memarpour B, Seyedi S, Farahani AV, Norouzi M, Karamian S, Zebardast A, Mehrabinia M, Ardekani OS, Fallah T, Khazry F, Daneshvar SF, Norouzi M. From discovery to treatment: tracing the path of hepatitis E virus. Virol J 2024; 21:194. [PMID: 39180020 PMCID: PMC11342613 DOI: 10.1186/s12985-024-02470-3] [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: 05/05/2024] [Accepted: 08/14/2024] [Indexed: 08/26/2024] Open
Abstract
The hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide. HEV is classified into eight genotypes, labeled HEV-1 through HEV-8. Genotypes 1 and 2 exclusively infect humans, while genotypes 3, 4, and 7 can infect both humans and animals. In contrast, genotypes 5, 6, and 8 are restricted to infecting animals. While most individuals with a strong immune system experience a self-limiting infection, those who are immunosuppressed may develop chronic hepatitis. Pregnant women are particularly vulnerable to severe illness and mortality due to HEV infection. In addition to liver-related complications, HEV can also cause extrahepatic manifestations, including neurological disorders. The immune response is vital in determining the outcome of HEV infection. Deficiencies in T cells, NK cells, and antibody responses are linked to poor prognosis. Interestingly, HEV itself contains microRNAs that regulate its replication and modify the host's antiviral response. Diagnosis of HEV infection involves the detection of HEV RNA and anti-HEV IgM/IgG antibodies. Supportive care is the mainstay of treatment for acute infection, while chronic HEV infection may be cleared with the use of ribavirin and pegylated interferon. Prevention remains the best approach against HEV, focusing on sanitation infrastructure improvements and vaccination, with one vaccine already licensed in China. This comprehensive review provides insights into the spread, genotypes, prevalence, and clinical effects of HEV. Furthermore, it emphasizes the need for further research and attention to HEV, particularly in cases of acute hepatitis, especially among solid-organ transplant recipients.
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Affiliation(s)
- Arash Letafati
- Department of Virology, Faculty of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran.
| | - Zahra Taghiabadi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Mahshid Roushanzamir
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
- Department of Pharmacological and Biomolecular Science, University of Milan, Milan, Italy
| | - Bahar Memarpour
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
- Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Saba Seyedi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | | | - Masoomeh Norouzi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Saeideh Karamian
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Arghavan Zebardast
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Marzieh Mehrabinia
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Omid Salahi Ardekani
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Tina Fallah
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Fatemeh Khazry
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Samin Fathi Daneshvar
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
| | - Mehdi Norouzi
- Department of Virology, Faculty of Public Health, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
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Alshiban NM, Aleyiydi MS, Nassar MS, Alhumaid NK, Almangour TA, Tawfik YM, Damiati LA, Almutairi AS, Tawfik EA. Epidemiologic and clinical updates on viral infections in Saudi Arabia. Saudi Pharm J 2024; 32:102126. [PMID: 38966679 PMCID: PMC11223122 DOI: 10.1016/j.jsps.2024.102126] [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] [Indexed: 07/06/2024] Open
Abstract
In the past two decades, the world has witnessed devastating pandemics affecting the global healthcare infrastructure and disrupting society and the economy worldwide. Among all pathogens, viruses play a critical role that is associated with outbreaks due to their wide range of species, involvement of animal hosts, easily transmitted to humans, and increased rates of infectivity. Viral disease outbreaks threaten public health globally due to the challenges associated with controlling and eradicating them. Implementing effective viral disease control programs starts with ongoing surveillance data collection and analyses to detect infectious disease trends and patterns, which is critical for maintaining public health. Viral disease control strategies include improved hygiene and sanitation facilities, eliminating arthropod vectors, vaccinations, and quarantine. The Saudi Ministry of Health (MOH) and the Public Health Authority (also known as Weqayah) in Saudi Arabia are responsible for public health surveillance to control and prevent infectious diseases. The notifiable viral diseases based on the Saudi MOH include hepatitis diseases, viral hemorrhagic fevers, respiratory viral diseases, exanthematous viral diseases, neurological viral diseases, and conjunctivitis. Monitoring trends and detecting changes in these viral diseases is essential to provide proper interventions, evaluate the established prevention programs, and develop better prevention strategies. Therefore, this review aims to highlight the epidemiological updates of the recently reported viral infections in Saudi Arabia and to provide insights into the recent clinical treatment and prevention strategies.
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Affiliation(s)
- Noura M. Alshiban
- Advanced Diagnostics and Therapeutics Institute, Health Sector, King Abdulaziz City for Science and Technology, Riyadh 11442, Saudi Arabia
| | - Munirah S. Aleyiydi
- Advanced Diagnostics and Therapeutics Institute, Health Sector, King Abdulaziz City for Science and Technology, Riyadh 11442, Saudi Arabia
| | - Majed S. Nassar
- Advanced Diagnostics and Therapeutics Institute, Health Sector, King Abdulaziz City for Science and Technology, Riyadh 11442, Saudi Arabia
| | - Nada K. Alhumaid
- Advanced Diagnostics and Therapeutics Institute, Health Sector, King Abdulaziz City for Science and Technology, Riyadh 11442, Saudi Arabia
| | - Thamer A. Almangour
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Yahya M.K. Tawfik
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Laila A. Damiati
- Department of Biological Sciences, College of Science, University of Jeddah, Jeddah 23218, Saudi Arabia
| | | | - Essam A. Tawfik
- Advanced Diagnostics and Therapeutics Institute, Health Sector, King Abdulaziz City for Science and Technology, Riyadh 11442, Saudi Arabia
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6
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Nagoba BS, Rayate AS. Hepatitis E virus infections. World J Virol 2024; 13:90951. [PMID: 38984082 PMCID: PMC11229837 DOI: 10.5501/wjv.v13.i2.90951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 03/02/2024] [Accepted: 04/07/2024] [Indexed: 06/24/2024] Open
Abstract
Hepatitis E virus (HEV) infection is now endemic worldwide. Most patients with acute infection recover uneventfully. Outbreaks and sporadic cases, particularly in high-risk individuals are emerging increasingly. The patients with risk factors like pregnancy and pre-existing chronic liver disease, present with or progress rapidly to severe disease. Immuno-suppression in post-transplant patients is an additional risk factor. Standardized FDA-approved diagnostic tests are the need of the hour. Further studies are needed to establish guideline-based treatment regimen and outbreak preparedness for HEV to decrease global morbidity, mortality, and healthcare burden. Policies for screening donors and transplant cases are required.
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Affiliation(s)
- Basavraj S Nagoba
- Department of Microbiology, Maharashtra Institute of Medical Sciences & Research (Medical College), Latur 413531, India
| | - Abhijit S Rayate
- Department of Surgery, Maharashtra Institute of Medical Sciences & Research (Medical College), Latur 413531, India
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Mukherjee R, Vidic J, Auger S, Wen HC, Pandey RP, Chang CM. Exploring Disease Management and Control through Pathogen Diagnostics and One Health Initiative: A Concise Review. Antibiotics (Basel) 2023; 13:17. [PMID: 38247576 PMCID: PMC10812768 DOI: 10.3390/antibiotics13010017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/20/2023] [Accepted: 12/20/2023] [Indexed: 01/23/2024] Open
Abstract
The "One Health" initiative is a critical strategy that recognizes the interconnectedness between human, animal, and environmental health in the spread and containment of infectious pathogens. With the ease of global transportation, transboundary disease outbreaks pose a significant threat to food safety and security, endangering public health and having a negative economic impact. Traditional diagnostic techniques based on genotypic and phenotypic analyses are expensive, time-consuming, and cannot be translated into point-of-care tools, hindering effective disease management and control. However, with advancements in molecular methods, biosensors, and new generation sequencing, rapid and reliable diagnostics are now available. This review provides a comprehensive insight into emergent viral and bacterial pathogens and antimicrobial resistance, highlighting the importance of "One Health" in connecting detection and effective treatment. By emphasizing the symbiotic relationship between human and animal health, this paper underscores the critical role of "One Health" initiatives in preventing and controlling infectious diseases.
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Affiliation(s)
- Riya Mukherjee
- Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan 33302, Taiwan;
- Master & Ph.D. Program in Biotechnology Industry, Chang Gung University, Taoyuan 33302, Taiwan
| | - Jasmina Vidic
- Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France; (J.V.); (S.A.)
| | - Sandrine Auger
- Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France; (J.V.); (S.A.)
| | - Hsiao-Chuan Wen
- Department of Pet Healthcare, Yuanpei University, Hsinchu 300, Taiwan;
| | - Ramendra Pati Pandey
- School of Health Sciences and Technology (SoHST), UPES, Dehradun 248007, Uttarakhand, India
| | - Chung-Ming Chang
- Master & Ph.D. Program in Biotechnology Industry, Chang Gung University, Taoyuan 33302, Taiwan
- Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan 33302, Taiwan
- Laboratory Animal Center, Chang Gung University, No. 259, Wenhua 1st Road, Guishan Dist., Taoyuan 33302, Taiwan
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Namdeo D, Shrivastava P, Garg G, Vyas AK, Nema RK, Singhai A, Nema S, Biswas D. Role of real-time polymerase chain reaction in diagnosing Hepatitis E, the commonest cause of acute hepatitis in adult patients seeking institutional care. INDIAN J PATHOL MICR 2023; 66:810-814. [PMID: 38084537 DOI: 10.4103/ijpm.ijpm_693_22] [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: 04/03/2023] Open
Abstract
Background This cross-sectional study was performed with the aim of determining the prevalence of hepatitis E virus (HEV) infection among acute hepatitis patients attending a tertiary care teaching hospital in a developing country and to determine the relative performance of prevalent diagnostic assays in establishing its diagnosis. Materials and Methods A total of 46 adult patients were included in this study, all of whom presented with jaundice of <4 weeks' duration and elevation of AST and ALT above 500 U/L. The prevalence of HEV among patients with acute hepatitis was calculated on the basis of the proportion of recruited patients reacting positively in serum anti-HEV immunoglobulin M (IgM) and real-time polymerase chain reaction (RT-PCR) assays. Results Among the recruited patients, 11 (23.91%) and 15 (32.6%) patients were positive for anti-HEV IgM and RT-PCR, respectively. The two tests demonstrated poor inter-test agreement, thereby implying the necessity of performing both tests for reliable diagnosis of acute HEV virus infection. We also observed a significant difference in the duration of illness between RT-PCR positive and negative patients (P = 0.008). The mean (±SD) duration of illness in the two groups was 8.6 (±3.50) and 11.66 (± 5.15) days, respectively. Combining the results of IgM ELISA and RT-PCR, we observed that 23 out of 46 patients (50%) had evidence of acute HEV virus infection among our patients. Conclusion Our study suggests that HEV is the commonest cause of acute hepatitis in adult patients attending a tertiary care teaching hospital and that the diagnostic algorithm for its confirmation should include both IgM ELISA and RT-PCR assays.
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Affiliation(s)
- Divya Namdeo
- Regional Virology Lab, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
| | - Pratima Shrivastava
- Department of Microbiology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
| | - Garima Garg
- Department of Microbiology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
| | - Ashish K Vyas
- Department of Microbiology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
| | - Ram K Nema
- Regional Virology Lab, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
| | - Abhishek Singhai
- Department of Medicine, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
| | - Shashwati Nema
- Regional Virology Lab; Departments of Microbiology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
| | - Debasis Biswas
- Regional Virology Lab; Departments of Microbiology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
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Fontana S, Ripellino P, Niederhauser C, Widmer N, Gowland P, Petrini O, Aprile M, Merlani G, Bihl F. Epidemiology of HEV Infection in Blood Donors in Southern Switzerland. Microorganisms 2023; 11:2375. [PMID: 37894033 PMCID: PMC10609445 DOI: 10.3390/microorganisms11102375] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 09/15/2023] [Accepted: 09/19/2023] [Indexed: 10/29/2023] Open
Abstract
From 2014 to 2016, the number of hepatitis E virus (HEV) infections in southern Switzerland increased dramatically and suggested food as a potential infection reservoir. We evaluated the effects of food control measures introduced to limit HEV infections, assessing anti-HEV IgG and IgM rates in blood donors before and after the implementation of food control measures in 2017. From 2012 to 2013, we screened 1283, and from 2017 to 2019, we screened 1447 donors for IgG and IgM antibodies. No statistically significant differences were detected for IgG (32.8% from 2012 to 2013 vs. 31.1% from 2017 to 2019, p = 0.337) or IgM rates (2.0% from 2012 to 2013 vs. 2.8% from 2017 to 2019, p = 0.21). Rural provenience and age > 66 are predictors for positive IgG serology. A total of 5.9% of 303 donors included in both groups lost IgG positivity. We also determined nucleic acid testing (NAT) rates after the introduction of this test in 2018, comparing 49,345 donation results from southern Switzerland with those of 625,559 Swiss donor controls, and only 9 NAT-positive donors were found from 2018 to 2023. The high HEV seroprevalence in southern Switzerland may depend on different food supply chains in rural and urban areas. Local preventive measures probably have a limited impact on blood HEV risk; thus, continuous NAT testing is recommended.
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Affiliation(s)
- Stefano Fontana
- Servizio Trasfusionale CRS della Svizzera Italiana, 6900 Lugano, Switzerland;
- Blood Transfusion Unit, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland
| | - Paolo Ripellino
- Department of Neurology, Neurocenter of Southern Switzerland EOC, 6900 Lugano, Switzerland;
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6900 Lugano, Switzerland
| | - Christoph Niederhauser
- Interregional Blood Transfusion SRC, 3008 Berne, Switzerland (N.W.); (P.G.)
- Institute for Infectious Diseases, University of Berne, 3008 Berne, Switzerland
| | - Nadja Widmer
- Interregional Blood Transfusion SRC, 3008 Berne, Switzerland (N.W.); (P.G.)
| | - Peter Gowland
- Interregional Blood Transfusion SRC, 3008 Berne, Switzerland (N.W.); (P.G.)
| | - Orlando Petrini
- Institute of Microbiology, University of Applied Sciences and Arts of Southern Switzerland, 6500 Bellinzona, Switzerland;
| | - Manuela Aprile
- Servizio Trasfusionale CRS della Svizzera Italiana, 6900 Lugano, Switzerland;
| | - Giorgio Merlani
- Chief Medical Officer Office, Division of Public Health, Department for Health and Social Affairs, 6500 Bellinzona, Switzerland;
| | - Florian Bihl
- Epatocentro Ticino, Via Soldino 5, 6900 Lugano, Switzerland;
- Division of Gastroenterology and Hepatology, University Hospital Geneva, 1200 Geneva, Switzerland
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Viera-Segura O, Calderón-Flores A, Batún-Alfaro JA, Fierro NA. Tracing the History of Hepatitis E Virus Infection in Mexico: From the Enigmatic Genotype 2 to the Current Disease Situation. Viruses 2023; 15:1911. [PMID: 37766316 PMCID: PMC10536485 DOI: 10.3390/v15091911] [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: 08/24/2023] [Revised: 09/09/2023] [Accepted: 09/10/2023] [Indexed: 09/29/2023] Open
Abstract
Hepatitis E virus (HEV) is the major cause of acute viral hepatitis worldwide. This virus is responsible for waterborne outbreaks in low-income countries and zoonosis transmission in industrialized regions. Initially, considered self-limiting, HEV may also lead to chronic disease, and evidence supports that infection can be considered a systemic disease. In the late 1980s, Mexico became a hot spot in the study of HEV due to one of the first virus outbreaks in Latin America related to enterically transmitted viral non-A, non-B hepatitis. Viral stool particles recovered from Mexican viral hepatitis outbreaks represented the first identification of HEV genotype (Gt) 2 (Gt2) in the world. No new findings of HEV-Gt2 have been reported in the country, whereas this genotype has been found in countries on the African continent. Recent investigations in Mexico have identified other strains (HEV-Gt1 and -Gt3) and a high frequency of anti-HEV antibodies in animal and human populations. Herein, the potential reasons for the disappearance of HEV-Gt2 in Mexico and the advances in the study of HEV in the country are discussed along with challenges in studying this neglected pathogen. These pieces of information are expected to contribute to disease control in the entire Latin American region.
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Affiliation(s)
- Oliver Viera-Segura
- Laboratorio de Diagnóstico de Enfermedades Emergentes y Reemergentes, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico
| | - Arturo Calderón-Flores
- Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
| | - Julio A. Batún-Alfaro
- Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
| | - Nora A. Fierro
- Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
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11
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Biswas S, Kumar R, Acharya SK, Shalimar. Prognostic Scores in Acute Liver Failure Due to Viral Hepatitis. Diagnostics (Basel) 2023; 13:1035. [PMID: 36980341 PMCID: PMC10047191 DOI: 10.3390/diagnostics13061035] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/02/2023] [Accepted: 03/04/2023] [Indexed: 03/11/2023] Open
Abstract
Viral infections are among the major causes of acute liver failure (ALF) worldwide. While the role of agents such as hepatitis A, B, C, D and E viruses in precipitating ALF are well known, improvements in serological assays have led to the detection of viral agents such as Epstein Barr virus, cytomegalovirus etc. as atypical causes of ALF. Despite the plethora of literature available on viral hepatitis and ALF, there is very limited large-scale epidemiologic data on the prevalence, risk factors of progression and outcomes in ALF of viral causes. This is important as viral infections remain the leading cause of ALF in the East and in developing countries, while the impact of viral ALF in the West has largely been ameliorated by effective vaccination and sanitization programs. This review focuses specifically on the available prognostic scores that aid in the management of ALF of viral etiologies while also briefly reviewing the current literature on newer viral agents known to cause ALF, risk factors of progression, outcomes and how management algorithms can be developed by incorporation of prognostic scoring systems for referral and transplant listing.
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Affiliation(s)
- Sagnik Biswas
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Bihar 801507, India
| | | | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, India
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12
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Hui W, Wei L. Treatment of Hepatitis E. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:215-226. [PMID: 37223869 DOI: 10.1007/978-981-99-1304-6_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Hepatitis E virus (HEV) infections are the most common cause of acute hepatitis, but they can also take a chronic course. There is no specific therapy for acute hepatitis, and current treatment is supportive. Choosing ribavirin as the first-line therapy for chronic HEV is advisable, especially immunosuppressed individuals. Moreover, ribavirin therapy in the acute phase of infection provides major benefits for those at high risk of acute liver failure (ALF)/acute-on-chronic liver failure (ACLF). Pegylated interferon α has been used successfully for treatment of hepatitis E but is associated with major side effects. Cholestasis is one of the most common, but devastating, manifestations in hepatitis E. Current therapy for HEV aims to treat symptoms. Therapy generally involves several measures, such as vitamins, albumin, and plasma for supporting treatment, symptomatic treatment for cutaneous pruritus, ursodeoxycholic acid, Obeticholic acid, S-adenosylmethionine, etc. for removing jaundice. HEV infection during pregnancy and patients with underlying liver disease may develop liver failure. For these patients, active monitoring, standard care, and supportive treatment are the foundations. Ribavirin has successfully been used to prevent liver transplantation (LT). Prevention and treatment of complications are important for treatment of liver failure. Liver support devices are intended to support liver function until such time as native liver function recovers, or until LT. LT is widely considered as irreplaceable and definitive treatment for liver failure, particularly for patients who do not improve with supportive measures to sustain life.
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Affiliation(s)
- Wei Hui
- Chronic Disease Management Center, Youan Hospital, Capital Medical University, Beijing, China
| | - Linlin Wei
- The Second Department of Liver Disease Center, Youan Hospital, Capital Medical University, Beijing, China.
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13
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Sero-epidemiology and Risk Assessment of Hepatitis E Virus Among Blood Donors in North Lebanon. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2022. [DOI: 10.5812/archcid-129115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: Hepatitis E virus (HEV) is the causative agent of over 50% of acute viral hepatitis cases. The blood transfusion route has emerged as a possible route of transmission of HEV. Objectives: This study aimed to determine the seroprevalence of IgM and IgG anti-HEV among blood donors in North Lebanon and to assess the risk factors associated with its occurrence. Methods: A cross-sectional study was conducted from November to December 2020. Blood samples were collected from 78 healthy blood donors. A standardized questionnaire containing sociodemographic, food consumption, lifestyle, and health-related characteristics, was filled out to assess the risk factors of HEV exposure. Serum samples were tested for IgM and IgG anti-HEV by an enzyme-linked immunosorbent assay (ELISA). Results: The seroprevalence of IgM and IgG anti-HEV antibodies was reported in our study, and it reached 1.09% (1/78) and 12.82% (10/78), respectively. The use of private wells as a drinking source and the travel history to endemic countries have been identified as risk factors for HEV infections (P
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14
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Chen C, Zhang SY, Chen L. Review of clinical characteristics, immune responses and regulatory mechanisms of hepatitis E-associated liver failure. World J Clin Cases 2022; 10:6341-6348. [PMID: 35979284 PMCID: PMC9294909 DOI: 10.12998/wjcc.v10.i19.6341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 03/17/2022] [Accepted: 05/07/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) is the most common cause of acute liver failure (LF) and one of the most common factors causing acute injury in acute-on-chronic LF (ACLF). When HEV-related LF occurs, a series of changes take place in both the intrahepatic environment and extrahepatic microenvironment. The changed types and distribution of immune cells (infiltrating macrophages and increased lymphocytes) in liver tissue, as well the increased proinflammatory cytokines and chemokines in the blood, indicate that the occurrence and progression of HEV-related LF are closely related to immune imbalance. The clinical features and immune reaction in the body during HEV-related acute LF (ALF) and ACLF are complicated. This review highlights recent progress in elucidating the clinical manifestations of HEV-associated ALF and ACLF and discusses the corresponding systemic immune changes and possible regulatory mechanisms.
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Affiliation(s)
- Chong Chen
- Department of Infectious Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
| | - Shu-Ye Zhang
- Department of Hepatology, Shanghai Public Health Clinical Center, Shanghai 201508, China
| | - Liang Chen
- Department of Hepatology, Shanghai Public Health Clinical Center, Shanghai 201508, China
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15
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Kim MB, Hwangbo S, Jang S, Jo YK. Bioengineered Co-culture of organoids to recapitulate host-microbe interactions. Mater Today Bio 2022; 16:100345. [PMID: 35847376 PMCID: PMC9283667 DOI: 10.1016/j.mtbio.2022.100345] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 06/26/2022] [Accepted: 06/27/2022] [Indexed: 11/05/2022] Open
Abstract
The recent spike in the instances of complex physiological host-microbe interactions has raised the demand for developing in vitro models that recapitulate the microbial microenvironment in the human body. Organoids are steadily emerging as an in vitro culture system that closely mimics the structural, functional, and genetic features of complex human organs, particularly for better understanding host-microbe interactions. Recent advances in organoid culture technology have become new avenues for assessing the pathogenesis of symbiotic interactions, pathogen-induced infectious diseases, and various other diseases. The co-cultures of organoids with microbes have shown great promise in simulating host-microbe interactions with a high level of complexity for further advancement in related fields. In this review, we provide an overview of bioengineering approaches for microbe-co-cultured organoids. Latest developments in the applications of microbe-co-cultured organoids to study human physiology and pathophysiology are also highlighted. Further, an outlook on future research on bioengineered organoid co-cultures for various applications is presented.
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16
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Serology as a Tool to Assess Infectious Disease Landscapes and Guide Public Health Policy. Pathogens 2022; 11:pathogens11070732. [PMID: 35889978 PMCID: PMC9323579 DOI: 10.3390/pathogens11070732] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Revised: 06/10/2022] [Accepted: 06/16/2022] [Indexed: 01/27/2023] Open
Abstract
Understanding the local burden and epidemiology of infectious diseases is crucial to guide public health policy and prioritize interventions. Typically, infectious disease surveillance relies on capturing clinical cases within a healthcare system, classifying cases by etiology and enumerating cases over a period of time. Disease burden is often then extrapolated to the general population. Serology (i.e., examining serum for the presence of pathogen-specific antibodies) has long been used to inform about individuals past exposure and immunity to specific pathogens. However, it has been underutilized as a tool to evaluate the infectious disease burden landscape at the population level and guide public health decisions. In this review, we outline how serology provides a powerful tool to complement case-based surveillance for determining disease burden and epidemiology of infectious diseases, highlighting its benefits and limitations. We describe the current serology-based technologies and illustrate their use with examples from both the pre- and post- COVID-19-pandemic context. In particular, we review the challenges to and opportunities in implementing serological surveillance in low- and middle-income countries (LMICs), which bear the brunt of the global infectious disease burden. Finally, we discuss the relevance of serology data for public health decision-making and describe scenarios in which this data could be used, either independently or in conjunction with case-based surveillance. We conclude that public health systems would greatly benefit from the inclusion of serology to supplement and strengthen existing case-based infectious disease surveillance strategies.
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17
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Modern Machine-Learning Predictive Models for Diagnosing Infectious Diseases. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:6902321. [PMID: 35693267 PMCID: PMC9185172 DOI: 10.1155/2022/6902321] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 04/03/2022] [Accepted: 05/26/2022] [Indexed: 12/16/2022]
Abstract
Controlling infectious diseases is a major health priority because they can spread and infect humans, thus evolving into epidemics or pandemics. Therefore, early detection of infectious diseases is a significant need, and many researchers have developed models to diagnose them in the early stages. This paper reviewed research articles for recent machine-learning (ML) algorithms applied to infectious disease diagnosis. We searched the Web of Science, ScienceDirect, PubMed, Springer, and IEEE databases from 2015 to 2022, identified the pros and cons of the reviewed ML models, and discussed the possible recommendations to advance the studies in this field. We found that most of the articles used small datasets, and few of them used real-time data. Our results demonstrated that a suitable ML technique depends on the nature of the dataset and the desired goal. Moreover, heterogeneous data could ensure the model's generalization, while big data, many features, and a hybrid model will increase the resulting performance. Furthermore, using other techniques such as deep learning and NLP to extract vast features from unstructured data is a powerful approach to enhancing the performance of ML diagnostic models.
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18
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Kovvuru K, Carbajal N, Pakanati AR, Thongprayoon C, Hansrivijit P, Boonpheng B, Pattharanitima P, Nissaisorakarn V, Cheungpasitporn W, Kanduri SR. Renal manifestations of hepatitis E among immunocompetent and solid organ transplant recipients. World J Hepatol 2022; 14:516-524. [PMID: 35582296 PMCID: PMC9055200 DOI: 10.4254/wjh.v14.i3.516] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 08/04/2021] [Accepted: 02/23/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) infections are generally self-limited. Rare cases of hepatitis E induced fulminant liver failure requiring liver transplantation are reported in the literature. Even though HEV infection is generally encountered among developing countries, a recent uptrend is reported in developed countries. Consumption of unprocessed meat and zoonosis are considered to be the likely transmission modalities in developed countries. Renal involvement of HEV generally holds a benign and self-limited course. Although rare cases of cryoglobulinemia are reported in immunocompetent patients, glomerular manifestations of HEV infection are frequently encountered in immunocompromised and solid organ transplant recipients. The spectrum of renal manifestations of HEV infection include pre-renal failure, glomerular disorders, tubular and interstitial injury. Kidney biopsy is the gold standard diagnostic test that confirms the pattern of injury. Management predominantly includes conservative approach. Reduction of immunosuppressive medications and ribavirin (for 3-6 mo) is considered among patients with solid organ transplants. Here we review the clinical course, pathogenesis, renal manifestations, and management of HEV among immunocompetent and solid organ transplant recipients.
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Affiliation(s)
- Karthik Kovvuru
- Department of Medicine, Ochsner Clinic Foundation, New Orleans, LA 70121, United States
| | - Nicholas Carbajal
- Department of Medicine, Ochsner Clinic Foundation, New Orleans, LA 70121, United States
| | | | - Charat Thongprayoon
- Department of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, United States
| | - Panupong Hansrivijit
- Department of Internal Medicine, UPMC Pinnacle, Harrisburg, PA 17104, United States
| | - Boonphiphop Boonpheng
- Department of Nephrology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States
| | - Pattharawin Pattharanitima
- Department of Internal Medicine, Faculty of Medicine, Thammasat University, Pathum Thani 12121, Thailand
| | - Voravech Nissaisorakarn
- Department of Internal Medicine, MetroWest Medical Center, Tufts University School of Medicine, Boston, MA 01760, United States
| | | | - Swetha R Kanduri
- Department of Medicine, Ochsner Clinic Foundation, New Orleans, LA 70121, United States
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19
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Cheung CKM, Wong SH, Law AWH, Law MF. Transfusion-transmitted hepatitis E: What we know so far? World J Gastroenterol 2022; 28:47-75. [PMID: 35125819 PMCID: PMC8793017 DOI: 10.3748/wjg.v28.i1.47] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 07/16/2021] [Accepted: 12/22/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) is a major cause of viral hepatitis globally. There is growing concern about transfusion-transmitted HEV (TT-HEV) as an emerging global health problem. HEV can potentially result in chronic infection in immunocompromised patients, leading to a higher risk of liver cirrhosis and even death. Between 0.0013% and 0.281% of asymptomatic blood donors around the world have HEV viremia, and 0.27% to 60.5% have anti-HEV immunoglobulin G. HEV is infectious even at very low blood concentrations of the virus. Immunosuppressed patients who develop persistent hepatitis E infection should have their immunosuppressant regimen reduced; ribavirin may be considered as treatment. Pegylated interferon can be considered in those who are refractory or intolerant to ribavirin. Sofosbuvir, a nucleotide analog, showed modest antiviral activity in some clinical studies but sustained viral response was not achieved. Therefore, rescue treatment remains an unmet need. The need for HEV screening of all blood donations remains controversial. Universal screening has been adopted in some countries after consideration of risk and resource availability. Various pathogen reduction methods have also been proposed to reduce the risk of TT-HEV. Future studies are needed to define the incidence of transmission through transfusion, their clinical features, outcomes and prognosis.
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Affiliation(s)
| | - Sunny Hei Wong
- Institute of Digestive Disease and Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong 852, China
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 639798, Singapore
| | | | - Man Fai Law
- Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
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20
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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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21
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Datfar T, Doulberis M, Papaefthymiou A, Hines IN, Manzini G. Viral Hepatitis and Hepatocellular Carcinoma: State of the Art. Pathogens 2021; 10:pathogens10111366. [PMID: 34832522 PMCID: PMC8619105 DOI: 10.3390/pathogens10111366] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 09/26/2021] [Accepted: 10/18/2021] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis is one of the main causes leading to hepatocellular carcinoma (HCC). The continued rise in incidence of HCC suggests additional factors following infection may be involved. This review examines recent studies investigating the molecular mechanisms of chronic hepatitis and its association with hepatocarcinogenesis. Hepatitis B virus patients with genotype C display an aggressive disease course leading to HCC more than other genotypes. Furthermore, hepatitis B excretory antigen (HBeAg) seems to be a more sensitive predictive tumor marker exhibiting a six-fold higher relative risk in patients with positive HBsAg and HBeAg than those with HBsAg only. Single or combined mutations of viral genome can predict HCC development in up to 80% of patients. Several mutations in HBx-gene are related with higher HCC incidence. Overexpression of the core protein in HCV leads to hepatocellular lipid accumulation associated with oncogenesis. Reduced number and decreased functionality of natural killer cells in chronic HCV individuals dysregulate their surveillance function in tumor and viral cells resulting in HCC. Furthermore, high T-cell immunoglobulin and mucin 3 levels supress CD8+ T-cells, which lead to immunological dysregulation. Hepatitis D promotes HCC development indirectly via modifications to innate immunity, epigenetic alterations and production of reactive oxygen species with the LHDAg being the most highly associated with HCC development. Summarizing the results, HBV and HCV infection represent the most associated forms of viral hepatitis causing HCC. Further studies are warranted to further improve the prediction of high-risk patients and development of targeted therapeutics preventing the transition from hepatic inflammation–fibrosis to cancer.
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Affiliation(s)
- Toofan Datfar
- Department of General and Visceral Surgery, Hospital of Aarau, 5001 Aarau, Switzerland;
- Correspondence: ; Tel.: +41-76-4930834
| | - Michael Doulberis
- Department of Gastroenterology and Hepatology, Hospital of Aarau, 5001 Aarau, Switzerland;
| | | | - Ian N. Hines
- Department of Nutrition Science, East Carolina University, Greenville, NC 27858, USA;
| | - Giulia Manzini
- Department of General and Visceral Surgery, Hospital of Aarau, 5001 Aarau, Switzerland;
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22
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Khuroo MS. Hepatitis E and Pregnancy: An Unholy Alliance Unmasked from Kashmir, India. Viruses 2021; 13:1329. [PMID: 34372535 PMCID: PMC8310059 DOI: 10.3390/v13071329] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 06/22/2021] [Accepted: 07/05/2021] [Indexed: 12/23/2022] Open
Abstract
The adverse relationship between viral hepatitis and pregnancy in developing countries had been interpreted as a reflection of retrospectively biased hospital-based data collection by the West. However, the discovery of hepatitis E virus (HEV) as the etiological agent of an epidemic of non-A, non-B hepatitis in Kashmir, and the documenting of the increased incidence and severity of hepatitis E in pregnancy via a house-to-house survey, unmasked this unholy alliance. In the Hepeviridae family, HEV-genotype (gt)1 from genus Orthohepevirus A has a unique open reading frame (ORF)4-encoded protein which enhances viral polymerase activity and viral replication. The epidemics caused by HEV-gt1, but not any other Orthohepevirus A genotype, show an adverse relationship with pregnancy in humans. The pathogenesis of the association is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the pregnant women including infection and damage to the maternal-fetal interface by HEV-gt1; vertical transmission of HEV to fetus causing severe fetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the pregnant women, promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of acute liver failure. (ALF). Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.
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Affiliation(s)
- Mohammad Sultan Khuroo
- Digestive Diseases Centre, Dr. Khuroo's Medical Clinic, Srinagar, Jammu and Kashmir 190010, India
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23
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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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