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Lu J, Li Q, Zhang C, Li Z, Guo Q, Cao Z, Yao YF, Xie Q. Heterogeneity in the seroprevalence of hepatitis E virus among hospital attendees: a retrospective study in Shanghai, China. Infect Dis (Lond) 2025:1-11. [PMID: 40017260 DOI: 10.1080/23744235.2025.2471819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 02/11/2025] [Accepted: 02/20/2025] [Indexed: 03/01/2025] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) infection is endemic in China. However, there are scarce data of HEV infection among hospital attendees seeking medical treatment or examination for various reasons. OBJECTIVE We aim to investigate the prevalence and incidence of HEV infection by time, age, sex, and across departments in a tertiary hospital. METHODS Paired results of anti-HEV immunoglobulin G (IgG) and IgM of 31,181 unique subjects during 2021-2022 were analysed. RESULTS Overall seropositivity (95% confidence interval) of anti-HEV IgG and IgM was 41.25% (40.71%-41.80%) and 2.35% (2.19%-2.53%), respectively. Acute hepatitis E was more prevalent during winter-early spring and among adults aged 31-70. Anti-HEV IgG seroprevalence increased with age, levelling off at > 60 years of age. Not only the seropositivity, but also the levels of anti-HEV IgG were significantly lower in women than men of middle and old age. Young patients from the Department of Neurology had a significantly higher ratio of past HEV infection, while patients with manifestations of hepatitis, gastrointestinal symptoms or hematological diseases had higher seropositivity of anti-HEVIgM and should have high priority to HEV screening. CONCLUSION Heterogeneity of HEV seroprevalence was noted at different times of the year, between sexes, among age groups and across departments in general hospital. The concentration of HEV-infected patients in a few departments supports a more focused screening strategy in health-care settings.
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Affiliation(s)
- Jie Lu
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Li
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chenxi Zhang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ziqiang Li
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Guo
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhujun Cao
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu-Feng Yao
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Laboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Ranković A, Cvetanović M, Miladinović J, Ćosić M, Popović Dragonjić L. Case report: Malaria and hepatitis E coinfection-first experience with such imported entity in Serbia. Front Med (Lausanne) 2024; 11:1498971. [PMID: 39697211 PMCID: PMC11653181 DOI: 10.3389/fmed.2024.1498971] [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: 09/19/2024] [Accepted: 11/18/2024] [Indexed: 12/20/2024] Open
Abstract
Acute hepatitis E virus (HEV) and malaria are not rare infections in tropical countries; however, in the European continent, such imported entity has not been reported up to now. Herein, we report a 24-year-old male suffering from malaria and hepatitis E, who was admitted with acute hepatic failure dark colored urine, followed by coagulation and inflammation parameters increase. Blood smear analysis revealed the presence of Plasmodium falciparum, while serological tests revealed anti-HEV IgM antibodies. After the recommended antimalarial drugs and supportive therapy, the patient survived and was discharged disease-free. Conclusions: Following WHO guidelines for the treatment of severe malaria, full recovery in patient was achieved.
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Affiliation(s)
- Aleksandar Ranković
- Department of Infectious Diseases and Epidemiology, Faculty of Medicine, University of Niš, Niš, Serbia
- Clinic for Infectology, University Clinical Center Niš, Niš, Serbia
| | - Maja Cvetanović
- Department of Infectious Diseases and Epidemiology, Faculty of Medicine, University of Niš, Niš, Serbia
- Clinic for Infectology, University Clinical Center Niš, Niš, Serbia
| | | | - Milica Ćosić
- Clinic for Infectology, University Clinical Center Niš, Niš, Serbia
| | - Lidija Popović Dragonjić
- Department of Infectious Diseases and Epidemiology, Faculty of Medicine, University of Niš, Niš, Serbia
- Clinic for Infectology, University Clinical Center Niš, Niš, Serbia
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3
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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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Mirzaev UK, Ko K, E B, Phyo Z, Chhoung C, Ataa AG, Sugiyama A, Akita T, Takahashi K, Tanaka J. Epidemiological assessment of hepatitis E virus infection among 1565 pregnant women in Siem Reap, Cambodia using an in-house double antigen sandwich ELISA. Hepatol Res 2024; 54:899-911. [PMID: 38573773 DOI: 10.1111/hepr.14041] [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: 01/20/2024] [Revised: 02/24/2024] [Accepted: 03/11/2024] [Indexed: 04/06/2024]
Abstract
AIM This study investigated hepatitis E virus (HEV) prevalence among pregnant women in Siem Reap, Cambodia, by developing a cost-effective, user-friendly in-house enzyme-linked immunosorbent assay (ELISA) for detecting total anti-HEV immunoglobulins (Ig). METHODS The in-house ELISA was designed for large-scale screening in resource-limited settings. Its performance was benchmarked against two commercial tests: the Anti-HEV IgG EIA (Institute of Immunology, Co. Ltd) and the Anti-HEV IgG RecomLine LIA (Mikrogen). The in-house ELISA demonstrated a sensitivity of 76% and 71.4%, and a specificity of 94.1% and 98.6%, against the two commercial tests, respectively, with overall agreement rates of 92.4% and 94.3%. RESULTS Among 1565 tested pregnant women, 11.6% were anti-HEV positive. Prevalence increased with age, particularly in women aged 35-40 years and over 40 years. No significant associations were found with education, number of children, family size, or history of blood transfusion and surgery, except for the occupation of the family head as a public officer. Of the total anti-HEV positive women, 22.7% had anti-HEV IgM, indicating recent or ongoing infection. CONCLUSION The study concluded that the in-house ELISA is a viable option for HEV screening in regions with limited resources due to its high accuracy and cost-effectiveness. It is particularly suitable for large-scale studies and public health interventions in areas where HEV is endemic and poses a significant risk to pregnant women.
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Affiliation(s)
- Ulugbek Khudayberdievich Mirzaev
- 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
- Department of Hepatology, Research Institute of Virology, Tashkent, Uzbekistan
| | - 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
| | - Bunthen E
- 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
- National Payment Certification Agency, Ministry of Economy and Finance, Phnom Penh, Cambodia
| | - 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
| | - 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
| | - Akuffo Golda Ataa
- 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
| | - 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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McSteen BW, Ying XH, Lucero C, Jesudian AB. Viral etiologies of acute liver failure. World J Virol 2024; 13:97973. [PMID: 39323454 PMCID: PMC11401000 DOI: 10.5501/wjv.v13.i3.97973] [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: 06/14/2024] [Revised: 08/07/2024] [Accepted: 08/19/2024] [Indexed: 08/29/2024] Open
Abstract
Acute liver failure (ALF) is a rare cause of liver-related mortality worldwide, with an estimated annual global incidence of more than one million cases. While drug-induced liver injury, including acetaminophen toxicity, is the leading cause of ALF in the Western world, viral infections remain a significant cause of ALF and the most common cause in many developing nations. Given the high mortality rates associated with ALF, healthcare providers should be aware of the broad range of viral infections that have been implicated to enable early diagnosis, rapid treatment initiation when possible, and optimal management, which may include liver transplantation. This review aims to provide a summary of viral causes of ALF, diagnostic approaches, treatment options, and expected outcomes.
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Affiliation(s)
- Brian W McSteen
- Department of Medicine, New York-Presbyterian/Weill Cornell Campus, New York, NY 10021, United States
| | - Xiao-Han Ying
- Department of Medicine, New York-Presbyterian/Weill Cornell Campus, New York, NY 10021, United States
| | - Catherine Lucero
- Department of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10021, United States
| | - Arun B Jesudian
- Department of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10021, United States
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6
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Shivangi, Mishra MK, Gupta S, Razdan K, Sudan S, Sehgal S. Clinical diagnosis of viral hepatitis: Current status and future strategies. Diagn Microbiol Infect Dis 2024; 108:116151. [PMID: 38184983 DOI: 10.1016/j.diagmicrobio.2023.116151] [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: 02/01/2023] [Revised: 08/15/2023] [Accepted: 11/24/2023] [Indexed: 01/09/2024]
Abstract
Viral hepatitis (VH) is a significant public health issue with tremendous potential to aggravate into chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Recent decade has witnessed remarkable uprising in the drug development and effective treatment of VH. An upsurge is seen in identification of antiviral therapies with low rates of viral resistance, the improvement of Hepatitis B Virus (HBV) vaccination and the development of direct-acting antivirals for Hepatitis C Virus (HCV). But unfortunately, the "2030 worldwide eradication" objective of World Health Organization (WHO) is still unmet. It can be largely attributed to the deficit faced by the healthcare system concerning screening and diagnosis. A timely, accurate and comprehensive screening; encompassing maximum population coverage is essential to combat this disease. However, advancements in VH diagnostics remain inadequate and with a marginal use in routine practice. This paper deliberates upon the lacunae in traditional and prevailing diagnostic methodology of viral hepatitis, especially their inadequacy in meeting the unique situations prevailing low- and middle-income countries (LMIC).
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Affiliation(s)
- Shivangi
- Centre for Molecular Biology, Central University of Jammu, Jammu (J&K), India
| | - Manish Kumar Mishra
- Centre for Molecular Biology, Central University of Jammu, Jammu (J&K), India
| | | | - Konika Razdan
- Government Medical College, Bakshi Nagar, Jammu, Jammu and Kashmir 180001, India
| | - Shashi Sudan
- Government Medical College, Bakshi Nagar, Jammu, Jammu and Kashmir 180001, India
| | - Shelly Sehgal
- Centre for Molecular Biology, Central University of Jammu, Jammu (J&K), India.
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Tang ZM, Wen GP, Ying D, Wang SL, Liu C, Tian WK, Wang YB, Fang MJ, Zhou YL, Ge YS, Wu T, Zhang J, Huang SJ, Zheng ZZ, Xia NS. Profile of clinical characteristics and serologic markers of sporadic hepatitis E in a community cohort study. Emerg Microbes Infect 2023; 12:2140613. [PMID: 36314245 PMCID: PMC9769141 DOI: 10.1080/22221751.2022.2140613] [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: 12/24/2022]
Abstract
Hepatitis E virus (HEV) is a pathogen of global significance, but the value of HEV-related markers in the diagnosis of hepatitis E remains controversial. Previous studies on hepatitis E profiles have been mainly cross-sectional and conducted among inpatients in large hospitals, and hepatitis E cases have been primarily defined by limited partial markers. In this community-based study, 4,110 active hepatitis cases from a population of nearly 600,000 were followed over 48 months and serial serum samples were collected. Both HEV pathogen (HEV RNA and antigen) and anti-HEV antibody markers were used to determine HEV infection status and the relationship between hepatitis and HEV infection. In total, 98 hepatitis E patients were identified and all available isolates from 58 patients belonged to HEV genotype 4. The mean age of the patients was 58.14 years, with an overwhelming proportion of males (70.4%). Hepatitis E accounted for 22.86% of active hepatitis cases with alanine aminotransferase levels ≥15.0-fold the upper limit of normal, suggesting the need to include HEV in routine testing for these patients. Ninety-two hepatitis E patients were positive for at least 2 of HEV antigen, anti-HEV IgM, and HEV RNA markers at presentation, and 90.22% of them were positive for HEV antigen and anti-HEV IgM. HEV antigen, HEV RNA, and anti-HEV IgM positivity were observed in 89.80%, 82.65%, and 93.88% of hepatitis E patients at presentation, respectively. However, only 57.14% of anti-HEV IgM positivity occurred in hepatitis E patients. These findings will advance our understanding of hepatitis E and improve diagnosis.
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Affiliation(s)
- Zi-Min Tang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China,NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China
| | - Gui-Ping Wen
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China,United Diagnostic and Research Center for Clinical Genetics, Women and Children's Hospital, School of Medicine and School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China
| | - Dong Ying
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China,School of Life Sciences, Xiamen University, Xiamen, PR People’s Republic of China
| | - Si-Ling Wang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China
| | - Chang Liu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China
| | - Wei-Kun Tian
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China
| | - Ying-Bin Wang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China
| | - Mu-Jin Fang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China,NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China
| | - Yu-Lin Zhou
- United Diagnostic and Research Center for Clinical Genetics, Women and Children's Hospital, School of Medicine and School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China
| | - Yun-Sheng Ge
- United Diagnostic and Research Center for Clinical Genetics, Women and Children's Hospital, School of Medicine and School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China
| | - Ting Wu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China
| | - Jun Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China
| | - Shou-Jie Huang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China, Shou-Jie Huang ; Zi-Zheng Zheng ; Ning-Shao Xia National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiangan South Road, Xiamen, Fujian, 361102, China
| | - Zi-Zheng Zheng
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China, Shou-Jie Huang ; Zi-Zheng Zheng ; Ning-Shao Xia National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiangan South Road, Xiamen, Fujian, 361102, China
| | - Ning-Shao Xia
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China,NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, Xiamen University, Xiamen, PR People’s Republic of China,School of Life Sciences, Xiamen University, Xiamen, PR People’s Republic of China, Shou-Jie Huang ; Zi-Zheng Zheng ; Ning-Shao Xia National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiangan South Road, Xiamen, Fujian, 361102, China
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8
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Jagirdhar GSK, Pulakurthi YS, Chigurupati HD, Surani S. Gastrointestinal tract and viral pathogens. World J Virol 2023; 12:136-150. [PMID: 37396706 PMCID: PMC10311582 DOI: 10.5501/wjv.v12.i3.136] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 03/17/2023] [Accepted: 04/27/2023] [Indexed: 06/21/2023] Open
Abstract
Viral gastroenteritis is the most common viral illness that affects the gastrointestinal (GI) tract, causing inflammation and irritation of the lining of the stomach and intestines. Common signs and symptoms associated with this condition include abdominal pain, diarrhea, and dehydration. The infections commonly involved in viral gastroenteritis are rotavirus, norovirus, and adenovirus, which spread through the fecal-oral and contact routes and cause non-bloody diarrhea. These infections can affect both immunocompetent and immunocompromised individuals. Since the pandemic in 2019, coronavirus gastroenteritis has increased in incidence and prevalence. Morbidity and mortality rates from viral gastroenteritis have declined significantly over the years due to early recognition, treatment with oral rehydration salts, and prompt vaccination. Improved sanitation measures have also played a key role in reducing the transmission of infection. In addition to viral hepatitis causing liver disease, herpes virus, and cytomegalovirus are responsible for ulcerative GI disease. They are associated with bloody diarrhea and commonly occur in im-munocompromised individuals. Hepatitis viruses, Epstein-Barr virus, herpesvirus 8, and human papillomavirus have been involved in benign and malignant diseases. This mini review aims to list different viruses affecting the GI tract. It will cover common symptoms aiding in diagnosis and various important aspects of each viral infection that can aid diagnosis and management. This will help primary care physicians and hospitalists diagnose and treat patients more easily.
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Affiliation(s)
| | | | | | - Salim Surani
- Department of Pulmonary, Critical Care and Sleep Medicine, Texas A&M University, College Station, TX 77843, United States
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9
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Lopez‐Lopez P, Frias M, Perez‐Jimenez AB, Freyre‐Carrillo C, Pineda JA, Aguilera A, Fuentes A, Alados JC, Reina G, Ramirez‐Arellano E, Viciana I, Mesquita J, Caballero‐Gomez J, Rivero‐Juarez A, Rivero A, for the HEPAVIR and GEHEP‐014 Study Groups. Optimization of the molecular diagnosis of the acute hepatitis E virus infection. Microb Biotechnol 2023; 16:1325-1332. [PMID: 36965117 PMCID: PMC10221520 DOI: 10.1111/1751-7915.14247] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 03/02/2023] [Accepted: 03/05/2023] [Indexed: 03/27/2023] Open
Abstract
To evaluate the diagnostic value of the combination of two broad-range PCR assays targeting two different and conserved regions of the viral genome for the diagnosis of acute Hepatitis E virus (HEV) infection. Patients with acute hepatitis were prospectively recruited. In all, HEV-IgM antibodies were tested together with evaluation of HEV viraemia by two PCR assays (ORF3 and ORF1). The number of individuals exhibiting negative IgM antibody results but carrying viral RNA was calculated by each PCR assay. Four-hundred and seventy individuals were included, of whom 145 (30.8%) were diagnosed as having acute HEV. Of them, 122 (84.1%) exhibited HEV-IgM antibodies, and 81 (55.8%) had detectable viral RNA for at least one PCR. Using the ORF3 molecular assay, 70 (48.3%) individuals were identified with HEV infection. When the ORF1 molecular assay was applied, 49 (33.8%) individuals were identified. The ORF3 assay detected viral RNA in 32 patients not detected by the ORF1 assay. In contrast, the ORF1 assay could amplify viral RNA in 11 patients who were not detected by the ORF3 assay. The parallel use of two broad-range PCR assays significantly increased the performance of the molecular diagnosis of HEV.
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Affiliation(s)
- Pedro Lopez‐Lopez
- Unit of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC)Universidad de Córdoba (UCO)CordobaSpain
- CIBERINFEC, ISCIII – CIBER de Enfermedades InfecciosasInstituto de Salud Carlos IIIMadridSpain
| | - Mario Frias
- Unit of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC)Universidad de Córdoba (UCO)CordobaSpain
- CIBERINFEC, ISCIII – CIBER de Enfermedades InfecciosasInstituto de Salud Carlos IIIMadridSpain
| | - Ana Belén Perez‐Jimenez
- CIBERINFEC, ISCIII – CIBER de Enfermedades InfecciosasInstituto de Salud Carlos IIIMadridSpain
- Clinical Microbiology UnitHospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)CórdobaSpain
| | | | - Juan A. Pineda
- CIBERINFEC, ISCIII – CIBER de Enfermedades InfecciosasInstituto de Salud Carlos IIIMadridSpain
- Unit of Infectious Diseases and Microbiology. Hospital Universitario de ValmeSevilleSpain
| | - Antonio Aguilera
- Microbiology DepartmentHospital Clínico Universitario & University of Santiago de Compostela (USC)/IDISSantiago de CompostelaSpain
| | - Ana Fuentes
- CIBERINFEC, ISCIII – CIBER de Enfermedades InfecciosasInstituto de Salud Carlos IIIMadridSpain
- Clinical Microbiology UnitHospital Universitario Clínico San Cecilio, Instituto de Investigacion Biosanitaria Ibs.GranadaSpain
| | | | - Gabriel Reina
- Microbiology DepartmentClínica Universidad de Navarra, ISTUN, Institute of Tropical Health, Universidad de Navarra, IdiSNA, Navarra Institute for Health ResearchPamplonaSpain
| | - Encarnación Ramirez‐Arellano
- Infectious Diseases, Microbiology and Preventive Medicine Unit, Department of MedicineVirgen Macarena Univ. Hospital, University of Sevilla/Biomedicine Institute of SevillaSevillaSpain
| | - Isabel Viciana
- Infectious Diseases, Microbiology and Preventive Medicine UnitHospital Universitario Virgen de la VictoriaMálagaSpain
| | - Joao Mesquita
- ICBAS – Instituto de Ciências Biomédicas Abel SalazarUniversidade do PortoPortoPortugal
- Epidemiology Research Unit (EPIUnit)Instituto de Saúde Pública da Universidade do PortoPortoPortugal
- Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR)PortoPortugal
| | - Javier Caballero‐Gomez
- Unit of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC)Universidad de Córdoba (UCO)CordobaSpain
- CIBERINFEC, ISCIII – CIBER de Enfermedades InfecciosasInstituto de Salud Carlos IIIMadridSpain
- Departamento Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEMUniversidad de CórdobaCórdobaSpain
| | - Antonio Rivero‐Juarez
- Unit of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC)Universidad de Córdoba (UCO)CordobaSpain
- CIBERINFEC, ISCIII – CIBER de Enfermedades InfecciosasInstituto de Salud Carlos IIIMadridSpain
| | - Antonio Rivero
- Unit of Infectious Diseases, Hospital Universitario Reina Sofia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC)Universidad de Córdoba (UCO)CordobaSpain
- CIBERINFEC, ISCIII – CIBER de Enfermedades InfecciosasInstituto de Salud Carlos IIIMadridSpain
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10
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Shafat Z, Ahmed A, Parvez MK, Parveen S. Intrinsic disorder in the open reading frame 2 of hepatitis E virus: a protein with multiple functions beyond viral capsid. J Genet Eng Biotechnol 2023; 21:33. [PMID: 36929465 PMCID: PMC10018590 DOI: 10.1186/s43141-023-00477-x] [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: 07/21/2022] [Accepted: 01/31/2023] [Indexed: 03/18/2023]
Abstract
BACKGROUND Hepatitis E virus (HEV) is the cause of a liver disease hepatitis E. The translation product of HEV ORF2 has recently been demonstrated as a protein involved in multiple functions besides performing its major role of a viral capsid. As intrinsically disordered regions (IDRs) are linked to various essential roles in the virus's life cycle, we analyzed the disorder pattern distribution of the retrieved ORF2 protein sequences by employing different online predictors. Our findings might provide some clues on the disorder-based functions of ORF2 protein that possibly help us in understanding its behavior other than as a HEV capsid protein. RESULTS The modeled three dimensional (3D) structures of ORF2 showed the predominance of random coils or unstructured regions in addition to major secondary structure components (alpha helix and beta strand). After initial scrutinization, the predictors VLXT and VSL2 predicted ORF2 as a highly disordered protein while the predictors VL3 and DISOPRED3 predicted ORF2 as a moderately disordered protein, thus categorizing HEV-ORF2 into IDP (intrinsically disordered protein) or IDPR (intrinsically disordered protein region) respectively. Thus, our initial predicted disorderness in ORF2 protein 3D structures was in excellent agreement with their predicted disorder distribution patterns (evaluated through different predictors). The abundance of MoRFs (disorder-based protein binding sites) in ORF2 was observed that signified their interaction with binding partners which might further assist in viral infection. As IDPs/IDPRs are targets of regulation, we carried out the phosphorylation analysis to reveal the presence of post-translationally modified sites. Prevalence of several disordered-based phosphorylation sites further signified the involvement of ORF2 in diverse and significant biological processes. Furthermore, ORF2 structure-associated functions revealed its involvement in several crucial functions and biological processes like binding and catalytic activities. CONCLUSIONS The results predicted ORF2 as a protein with multiple functions besides its role as a capsid protein. Moreover, the occurrence of IDPR/IDP in ORF2 protein suggests that its disordered region might serve as novel drug targets via functioning as potential interacting domains. Our data collectively might provide significant implication in HEV vaccine search as disorderness in viral proteins is related to mechanisms involved in immune evasion.
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Affiliation(s)
- Zoya Shafat
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
| | - Anwar Ahmed
- Centre of Excellence in Biotechnology Research, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Mohammad K. Parvez
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Shama Parveen
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
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11
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Zhao C, Wang Y. Laboratory Diagnosis of HEV Infection. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:199-213. [PMID: 37223868 DOI: 10.1007/978-981-99-1304-6_14] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Serological and nucleic acid tests for detecting hepatitis E virus (HEV) have been developed for both epidemiologic and diagnostic purposes. The laboratory diagnosis of HEV infection depends on the detection of HEV antigen or HEV RNA in the blood, stool, and other body fluids, and serum antibodies against HEV (immunoglobulin [Ig]A, IgM, and IgG). Anti-HEV IgM antibodies and low avidity IgG can be detected during the acute phase of the illness and can last approximately 12 months, representing primary infection, whereas anti-HEV IgG antibodies can last more than several years, representing remote exposure. Thus, the diagnosis of acute infection is based on the presence of anti-HEV IgM, low avidity IgG, HEV antigen, and HEV RNA, while epidemiological investigations are mainly based on anti-HEV IgG. Although significant progress has been made in developing and optimizing different formats of HEV assays, improving their sensitivity and specificity, there are many shortcomings and challenges in inter-assay concordance, validation, and standardization. This article reviews the current knowledge on the diagnosis of HEV infection, including the most common available laboratory diagnostic techniques.
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Affiliation(s)
- Chenyan Zhao
- Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing, China
| | - Youchun Wang
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, China.
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12
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Ying D, He Q, Tian W, Chen Y, Zhang X, Wang S, Liu C, Chen Z, Liu Y, Fu L, Yan L, Wang L, Tang Z, Wang L, Zheng Z, Xia N. Urine is a viral antigen reservoir in hepatitis E virus infection. Hepatology 2022; 77:1722-1734. [PMID: 36106666 DOI: 10.1002/hep.32745] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Revised: 08/16/2022] [Accepted: 08/18/2022] [Indexed: 12/08/2022]
Abstract
BACKGROUND AND AIMS HEV ORF2 antigen (Ag) in serum has become a tool for diagnosing current HEV infection. Particularly, urinary shedding of HEV Ag has been gaining increasing interest. We aim to uncover the origin, antigenicity, diagnostic performance, and diagnostic significance of Ag in urine in HEV infection. APPROACH AND RESULTS Clinical serum and urine samples from patients with acute and chronic HEV infection were analyzed for their Ag levels. Ag in urine was analyzed by biochemical and proteomic approaches. The origin of urinary Ag and Ag kinetics during HEV infection was investigated in mouse and rabbit models, respectively. We found that both the Ag level and diagnostic sensitivity in urine were higher than in serum. Antigenic protein in urine was an E2s-like dimer spanning amino acids 453-606. pORF2 entered urine from serum in mice i.v. injected with pORF2. Ag in urine originated from the secreted form of pORF2 (ORF2S ) that abundantly existed in hepatitis E patients' serum. HEV Ag was specifically taken up by renal cells and was disposed into urine, during which the level of Ag was concentrated >10-fold, resulting in the higher diagnosing sensitivity of urine Ag than serum Ag. Moreover, Ag in urine appeared 6 days earlier, lasted longer than viremia and antigenemia, and showed good concordance with fecal RNA in a rabbit model. CONCLUSIONS Our findings demonstrated the origin and diagnostic value of urine Ag and provided insights into the disposal of exogenous protein of pathogens by the host kidney.
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Affiliation(s)
- Dong Ying
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, PR China
| | - Qiyu He
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China
| | - Weikun Tian
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, PR China
| | - Yanling Chen
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, PR China
| | - Xiaoping Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, PR China
| | - Siling Wang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, PR China
| | - Chang Liu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, PR China
| | - Zihao Chen
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, PR China
| | - Yu Liu
- Department of Severe Hepatopathy, Shanghai Public Health Clinical Center, Fudan University, Shanghai, PR China
| | - Lijuan Fu
- Department of Infectious Disease, Xiang'an Hospital of Xiamen University, Xiamen, PR China
| | - Li Yan
- Department of Severe Hepatopathy, Shanghai Public Health Clinical Center, Fudan University, Shanghai, PR China
| | - Ling Wang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China
| | - Zimin Tang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, PR China.,NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, Xiamen University, Xiamen, PR China
| | - Lin Wang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China
| | - Zizheng Zheng
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, PR China
| | - Ningshao Xia
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, PR China
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13
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Qashqari FS. Seroprevalence of Hepatitis E Virus Infection in Middle Eastern Countries: A Systematic Review and Meta-Analysis. Medicina (B Aires) 2022; 58:medicina58070905. [PMID: 35888624 PMCID: PMC9318471 DOI: 10.3390/medicina58070905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 07/02/2022] [Accepted: 07/04/2022] [Indexed: 11/25/2022] Open
Abstract
Hepatitis E virus (HEV) is a hepatotropic virus that is a major public health concern worldwide. Autochthonous HEV is spread through oral feces in unsanitary environments, as well as vertical and, occasionally, blood transfusion. HEV is more common in developing countries, but it has recently become more widespread in developed countries as well. The Middle East (ME) has long been an endemic location for HEV infection. Therefore, the aim of this systematic review and meta-analysis was to assess the seroprevalence of anti-HEV antibodies in ME countries. The author systematically searched five databases, namely ScienceDirect, EMBASE, Scopus, PubMed, and Google Scholar, to identify English-language articles published on or before 25 April 2022. Comprehensive meta-analysis software was used for all statistical analyses (CMA, version 3, BioStat, Englewood, CO, USA). After quality control and exclusion of irrelevant studies, 80 studies were included in the qualitative synthesis and meta-analysis. A forest plot showed that the overall pooled seroprevalence of HEV infection in ME countries in the fixed-effect and random-effect models were 21.3% (95% CI: 0.209–0.216) and 11.8% (95% CI: 0.099–0.144), respectively. Furthermore, the findings showed a high level of heterogeneity (I2 = 98.733%) among the included studies. In both fixed-effect and random-effect models, the seroprevalence of HEV infection by country was high in Egypt as compared to other regions, at 35.0% (95% CI: 0.342–0.359), and 34.7% (95% CI: 0.153–0.611), respectively. The seroprevalence of HEV infection by country was high among pregnant women, at 47.9% (95% CI: 0.459–0.499) in the fixed-effect model, and in renal transplant recipients, at 30.8% (95% CI: 0.222–0.410) in the random-effect model. The seroprevalence of HEV infection varies by country and study population in the Middle East. More research is needed to determine the disease’s incidence, morbidity, and mortality in the region, where it is prevalent.
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Affiliation(s)
- Fadi S Qashqari
- Department of Microbiology, College of Medicine, Umm Al-Qura University, Makkah 24381, Saudi Arabia
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14
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Pérez-García F, Vázquez-Morón S, Burgueño-García I, José Muñoz-Gómez M, Zea-Sevilla MA, Calero M, Martínez I, Rábano A, Resino S. Hepatitis E virus seroprevalence is associated with neurodegenerative disorders in older people with dementia: a case-control study. J Infect Dis 2022; 227:873-877. [PMID: 35759220 DOI: 10.1093/infdis/jiac268] [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: 03/03/2022] [Revised: 05/16/2022] [Accepted: 06/24/2022] [Indexed: 11/12/2022] Open
Abstract
In this case-control study, we evaluated the association between serum antibodies against hepatitis E virus (HEV) and central nervous system (CNS) neurodegenerative disorders (NDs) in older people with dementia. The presence of anti-HEV antibodies was related to a higher adjusted odds ratio (aOR) of having CNS-NDs by neuropathological diagnosis (aOR = 2.13; p = 0.007) and clinical/neuropathological diagnosis (aOR = 1.84; p = 0.017). Besides, serum anti-HEV antibodies were directly related to neuropathological injury (higher vascular pathology, aOR = 1.97; p = 0.006) and higher probability of having Alzheimer-type pathology (aOR = 1.84; p = 0.022). In conclusion, the presence of anti-HEV antibodies was related to higher odds of CNS-NDs and neuropathological injury in older people.
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Affiliation(s)
- Felipe Pérez-García
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain.,Servicio de Microbiología Clínica, Hospital Universitario Príncipe de Asturias, Madrid, Spain.,Universidad de Alcalá, Facultad de Medicina, Departamento de Biomedicina y Biotecnología, Madrid, Spain
| | - Sonia Vázquez-Morón
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain
| | - Iván Burgueño-García
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
| | - María José Muñoz-Gómez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain
| | - María Ascensión Zea-Sevilla
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
| | - Miguel Calero
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.,Unidad Funcional Investigación de Enfermedades Crónicas, Instituto de Salud Carlos III, Majadahonda, Spain.,Banco de Tejidos, Departamento de Neuropatología, Fundación Centro de Investigación en Enfermedades Neurológicas, Instituto de Salud Carlos III (FCIEN-ISCIII), Madrid, Spain
| | - Isidoro Martínez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain.,Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Alberto Rábano
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.,Banco de Tejidos, Departamento de Neuropatología, Fundación Centro de Investigación en Enfermedades Neurológicas, Instituto de Salud Carlos III (FCIEN-ISCIII), Madrid, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain.,Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
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15
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Emeriaud H, Huet F, Roubille F, Pasquié JL. Acute myocarditis induced by Hepatitis E: an uncommon association. CJC Open 2022; 4:729-731. [PMID: 36035732 PMCID: PMC9402964 DOI: 10.1016/j.cjco.2022.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 04/25/2022] [Indexed: 11/30/2022] Open
Abstract
Acute myocarditis is often caused by viral infections. Hepatitis E infection inflicts over 20 million people worldwide each year. Common extra-hepatic manifestations of hepatitis E infection include neurologic, hematologic, and renal sequelae.1 Acute myocarditis, defined by the presence of myocardial inflammatory infiltrates associated with nonischemic myocytic necrosis, is uncommon. Published reports of such cases are limited, and here we present the case of a 45-year-old man with acute myocarditis from hepatitis E infection. This case is the first described in Europe of acute myocarditis associated with hepatitis E infection.
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Affiliation(s)
- Héloïse Emeriaud
- Department of Cardiology, Montpellier University Hospital, Montpellier, France
- Corresponding author: Héloïse Emeriaud, Cardiology Department, Hôpital Arnaud de Villeneuve, CHU de Montpellier, 191 avenue du Doyen Gaston Giraud, Montpellier, France.
| | - Fabien Huet
- PhyMedExp, Université de Montpellier, INSERM, CNRS, Cardiology Department, CHU de Montpellier, Montpellier, France
- Department of Cardiology, Vannes Regional Hospital, Vannes, France
| | - François Roubille
- Department of Cardiology, Montpellier University Hospital, Montpellier, France
- PhyMedExp, Université de Montpellier, INSERM, CNRS, Cardiology Department, CHU de Montpellier, Montpellier, France
| | - Jean-Luc Pasquié
- Department of Cardiology, Montpellier University Hospital, Montpellier, France
- PhyMedExp, Université de Montpellier, INSERM, CNRS, Cardiology Department, CHU de Montpellier, Montpellier, France
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16
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Fang L, Zhang J, Chen H, Lv F, Yu Y, Du X. Epidemiological Characteristics and Clinical Manifestations of Hepatitis E in a Tertiary Hospital in China: A Retrospective Study. Front Microbiol 2022; 12:831968. [PMID: 35310389 PMCID: PMC8928388 DOI: 10.3389/fmicb.2021.831968] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 12/31/2021] [Indexed: 01/12/2023] Open
Abstract
Background Hepatitis E virus (HEV) infection is the most common cause of acute viral hepatitis worldwide and one of the main causes of death in the last decade, causing chronic hepatitis and liver failure in some populations. The aging population and obesity are two major factors threatening human health. Therefore, we want to understand the relationship between these two groups and HEV infection. Objectives The study aimed to analyze the epidemiological, clinical, and laboratory features of HEV infection and evaluate probable high-risk factors for disease progression and the current diagnostic strategies of hepatitis E infection. Study Design Patients diagnosed with acute hepatitis E with symptoms and liver dysfunction were enrolled. For statistical analysis, clinical features and laboratory findings were collected between the elderly and non-elderly and HEV+ fatty liver disease (FLD) groups. Statistical analysis was performed using Excel and the platform VassarStats, and statistical significance was taken as P < 0.05. Results Jaundice and the bilirubin peak were significantly deeper, the duration of hospitalization was significantly longer, and the proportion of ascites and liver failure was significantly higher in the elderly group. The aging population is one of the risk factors of severe hepatitis E. Hepatitis E becomes more serious in the HEV + FLD group, although the results did not reach statistical significance. Conclusion The aging and FLD were suggested to aggravate HEV infection. However, the diagnosis of HEV infection remains a challenge. A prospective study with sufficient sample size is needed to confirm this conclusion.
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Affiliation(s)
- Li Fang
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Junli Zhang
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Huiying Chen
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Fangfang Lv
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yunsong Yu
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiaoxing Du
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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17
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Sintusek P, Thanapirom K, Komolmit P, Poovorawan Y. Eliminating viral hepatitis in children after liver transplants: How to reach the goal by 2030. World J Gastroenterol 2022; 28:290-309. [PMID: 35110951 PMCID: PMC8771616 DOI: 10.3748/wjg.v28.i3.290] [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: 06/03/2021] [Revised: 08/12/2021] [Accepted: 01/06/2022] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis infections are a great burden in children who have received liver transplant. Hepatotropic viruses can cause liver inflammation that can develop into liver graft fibrosis and cirrhosis over the long term. Immunological reactions due to viral hepatitis infections are associated with or can mimic graft rejection, rendering the condition difficult to manage. Prevention strategies using vaccinations are agreeable to patients, safe, cost-effective and practical. Hence, strategies to eliminate viral hepatitis A and B focus mainly on immunization programmes for children who have received a liver transplant. Although a vaccine has been developed to prevent hepatitis C and E viruses, its use is not licensed worldwide. Consequently, eliminating hepatitis C and E viruses mainly involves early detection in children with suspected cases and effective treatment with antiviral therapy. Good hygiene and sanitation are also important to prevent hepatitis A and E infections. Donor blood products and liver grafts should be screened for hepatitis B, C and E in children who are undergoing liver transplantation. Future research on early detection of viral hepatitis infections should include molecular techniques for detecting hepatitis B and E. Moreover, novel antiviral drugs for eradicating viral hepatitis that are highly effective and safe are needed for children who have undergone liver transplantation.
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Affiliation(s)
- Palittiya Sintusek
- The Thai Pediatric Gastroenterology, Hepatology and Immunology (TPGHAI) Research Unit, Chulalongkorn University, Bangkok 10330, Thailand
- Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Kessarin Thanapirom
- Division of Gastroenterology, Department of Medicine, Liver Fibrosis and Cirrhosis Research Unit, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Piyawat Komolmit
- Division of Gastroenterology, Department of Medicine, Liver Fibrosis and Cirrhosis Research Unit, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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18
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Zitelli PMY, Gomes-Gouvêa M, Mazo DF, Singer JDM, Oliveira CP, Farias AQ, Pinho JR, Tanigawa RY, Alves VAF, Carrilho FJ, Pessoa MG. Hepatitis E virus infection increases the risk of diabetes and severity of liver disease in patients with chronic hepatitis C virus infection. Clinics (Sao Paulo) 2021; 76:e3270. [PMID: 34852140 PMCID: PMC8595601 DOI: 10.6061/clinics/2021/e3270] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 09/21/2021] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES Co-infection with hepatitis A or B viruses may aggravate liver injury in patients infected with hepatitis C virus (HCV). However, few studies have assessed co-infection with hepatitis E virus (HEV) and HCV. Therefore, this study aimed to assess the prevalence and impact of HEV infection among Brazilian patients with chronic HCV infection. METHODS This observational study included adult patients with chronic HCV infection who were naive to antiviral therapy from January 2013 to March 2016. A total of 181 patients were enrolled, and HEV serology and PCR were performed for all patients. RESULTS Seropositivity for anti-HEV IgG was detected in 22 (12.0%) patients and anti-HEV immunoglobulin M in 3 (1.6%). HEV RNA showed inconclusive results in nine (4.9%) patients and was undetectable in the remaining patients. HEV serology positive patients had more severe liver disease, characterized by liver fibrosis ≥3 versus ≤2 (p<0.001), Aspartate Aminotransferase-to-Platelet Ratio Index of ≥1.45 (p=0.003), and Fibrosis-4 score of ≥3.25 (p=0.001). Additionally, the odds of HEV-positive patients developing diabetes mellitus were 3.65 (95% CI 1.40-9.52) times the corresponding odds of HEV-negative patients. A case-control-based histological analysis (n=11 HEV-HCV-positive patients and n=22 HCV-positive patients) showed no significant differences between the groups. CONCLUSIONS This prevalence is higher than that reported in previous studies of the general population in Brazil. Thus, HEV infection may influence the severity of liver disease and may represent an additional risk of developing diabetes mellitus in patients with HCV infection.
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Affiliation(s)
- Patricia Momoyo Yoshimura Zitelli
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Michele Gomes-Gouvêa
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Daniel F. Mazo
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
- Divisao de Gastroenterologia (Gastrocentro), Faculdade de Ciencias Medicas, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, BR
| | - Julio da Motta Singer
- Departamento de Estatistica, Instituto de Matematica e Estatistica, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Claudia P.M.S. Oliveira
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Alberto Queiroz Farias
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - João Renato Pinho
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Ryan Yukimatsu Tanigawa
- Departamento de Patologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | | | - Flair José Carrilho
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Mário Guimarães Pessoa
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
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19
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Shafat Z, Ahmed A, Parvez MK, Parveen S. Role of "dual-personality" fragments in HEV adaptation-analysis of Y-domain region. J Genet Eng Biotechnol 2021; 19:154. [PMID: 34637041 PMCID: PMC8511232 DOI: 10.1186/s43141-021-00238-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 08/30/2021] [Indexed: 01/06/2023]
Abstract
BACKGROUND Hepatitis E is a liver disease caused by the pathogen hepatitis E virus (HEV). The largest polyprotein open reading frame 1 (ORF1) contains a nonstructural Y-domain region (YDR) whose activity in HEV adaptation remains uncharted. The specific role of disordered regions in several nonstructural proteins has been demonstrated to participate in the multiplication and multiple regulatory functions of the viruses. Thus, intrinsic disorder of YDR including its structural and functional annotation was comprehensively studied by exploiting computational methodologies to delineate its role in viral adaptation. RESULTS Based on our findings, it was evident that YDR contains significantly higher levels of ordered regions with less prevalence of disordered residues. Sequence-based analysis of YDR revealed it as a "dual personality" (DP) protein due to the presence of both structured and unstructured (intrinsically disordered) regions. The evolution of YDR was shaped by pressures that lead towards predominance of both disordered and regularly folded amino acids (Ala, Arg, Gly, Ile, Leu, Phe, Pro, Ser, Tyr, Val). Additionally, the predominance of characteristic DP residues (Thr, Arg, Gly, and Pro) further showed the order as well as disorder characteristic possessed by YDR. The intrinsic disorder propensity analysis of YDR revealed it as a moderately disordered protein. All the YDR sequences consisted of molecular recognition features (MoRFs), i.e., intrinsic disorder-based protein-protein interaction (PPI) sites, in addition to several nucleotide-binding sites. Thus, the presence of molecular recognition (PPI, RNA binding, and DNA binding) signifies the YDR's interaction with specific partners, host membranes leading to further viral infection. The presence of various disordered-based phosphorylation sites further signifies the role of YDR in various biological processes. Furthermore, functional annotation of YDR revealed it as a multifunctional-associated protein, due to its susceptibility in binding to a wide range of ligands and involvement in various catalytic activities. CONCLUSIONS As DP are targets for regulation, thus, YDR contributes to cellular signaling processes through PPIs. As YDR is incompletely understood, therefore, our data on disorder-based function could help in better understanding its associated functions. Collectively, our novel data from this comprehensive investigation is the first attempt to delineate YDR role in the regulation and pathogenesis of HEV.
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Affiliation(s)
- Zoya Shafat
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
| | - Anwar Ahmed
- Centre of Excellence in Biotechnology Research, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Mohammad K. Parvez
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Shama Parveen
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
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20
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Elbahrawy A, Ibrahim MK, Eliwa A, Alboraie M, Madian A, Aly HH. Current situation of viral hepatitis in Egypt. Microbiol Immunol 2021; 65:352-372. [PMID: 33990999 DOI: 10.1111/1348-0421.12916] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/02/2021] [Accepted: 05/11/2021] [Indexed: 12/12/2022]
Abstract
An estimated 8-10 million people suffer from viral hepatitis in Egypt. Hepatitis A virus (HAV) and hepatitis E virus (HEV) are the major causes of viral hepatitis in Egypt as 50% or more of the Egyptian population are already exposed to HAV infection by the age of 15. In addition, over 60% of the Egyptian population test seropositive for anti-HEV in the first decade of life. HEV mainly causes self-limiting hepatitis; however, cases of fulminant hepatitis and liver failure were reported in Egypt. Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV) are the main causes of chronic hepatitis, liver cirrhosis, and liver cancer (hepatocellular carcinoma [HCC]) in Egypt. Globally, Egypt had the highest age-standardized death rate due to cirrhosis from 1990 to 2017. The prevalence rate of HBV (1.3%-1.5%) has declined after national infantile immunization. Coinfection of HBV patients with HDV is common in Egypt because HDV antibodies (IgG) vary in range from 8.3% to 43% among total HBV patients. After the conduction of multiple national programs to control HCV infection, a lower rate of HCV prevalence (4.6%) was recently reported. Data about the incidence of HCV after treatment with direct antiviral agents (DAAs) are lacking. An HCC incidence of 29/1000/year in cirrhotic patients after DAA treatment is reported. A higher rate of infiltrative pattern among HCC patients after DAA treatment is also recognized. Viral hepatitis is one of the major public health concerns in Egypt that needs more attention and funding from health policymakers.
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Affiliation(s)
- Ashraf Elbahrawy
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
| | - Marwa K Ibrahim
- Department of Microbial Biotechnology, Division of Genetic Engineering and Biotechnology Research, National Research Centre, Giza, Egypt
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Ahmed Eliwa
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
| | - Mohamed Alboraie
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
| | - Ali Madian
- Department of Internal Medicine, Al-Azhar University, Assiut, Egypt
| | - Hussein Hassan Aly
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
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21
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Fritz-Weltin M, Frommherz E, Isenmann N, Niedermeier L, Csernalabics B, Boettler T, Neumann-Haefelin C, Endres D, Panning M, Berger B. Hepatitis E virus as a trigger for Guillain-Barré syndrome. BMC Neurol 2021; 21:304. [PMID: 34362318 PMCID: PMC8343920 DOI: 10.1186/s12883-021-02334-1] [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: 03/14/2021] [Accepted: 07/26/2021] [Indexed: 12/24/2022] Open
Abstract
Background Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. An association with neuralgic amyotrophy and Guillain-Barré syndrome (GBS) was previously described. Concerning GBS, studies from other countries found an acute HEV infection in 5–11% of cases. However, HEV prevalence shows considerable regional variations. Therefore, we retrospectively analyzed the frequency of HEV infections in association with GBS in a monocentric cohort in Southwestern Germany. Methods Overall, 163 patients with GBS treated in our clinic between 2008 and 2018 of whom serum and/or cerebrospinal fluid (CSF) samples were available, were identified. Serum samples were analyzed for anti-HEV immunoglobulin (Ig)M and IgG antibodies by ELISA. Additionally, both serum and cerebrospinal fluid (CSF) samples were tested for HEV RNA by PCR if IgM was positive or patients presented within the first 7 days from GBS symptom onset. A group of 167 healthy volunteers and 96 healthy blood donors served as controls. Results An acute HEV infection was found in two GBS patients (1.2%) with anti-HEV IgM and IgG antibodies. HEV PCR in serum and CSF was negative in these two patients as well as in all other tested cases. Seroprevalences indicated that acute infection did not differ significantly from controls (0.8%). Anti-HEV IgG seroprevalence indicating previous infection was unexpectedly high (41%) and revealed an age-dependent increase to more than 50% in patients older than 60 years. Conclusion In this study, serological evidence of an acute HEV infection in patients with GBS was rare and not different from controls. Comparing our data with previous studies, incidence rates show considerable regional variations.
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Affiliation(s)
- Miriam Fritz-Weltin
- Clinic of Neurology and Neurophysiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany
| | - Estelle Frommherz
- Clinic of Neurology and Neurophysiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany
| | - Nora Isenmann
- Clinic of Neurology and Neurophysiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany
| | - Lisa Niedermeier
- Clinic of Neurology and Neurophysiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany
| | - Benedikt Csernalabics
- Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Tobias Boettler
- Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Christoph Neumann-Haefelin
- Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Dominique Endres
- Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Marcus Panning
- Institute of Virology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Benjamin Berger
- Clinic of Neurology and Neurophysiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany.
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22
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Velavan TP, Pallerla SR, Johne R, Todt D, Steinmann E, Schemmerer M, Wenzel JJ, Hofmann J, Shih JWK, Wedemeyer H, Bock CT. Hepatitis E: An update on One Health and clinical medicine. Liver Int 2021; 41:1462-1473. [PMID: 33960603 DOI: 10.1111/liv.14912] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 03/09/2021] [Accepted: 04/08/2021] [Indexed: 12/12/2022]
Abstract
The hepatitis E virus (HEV) is one of the main causes of acute hepatitis and the de facto global burden is underestimated. HEV-related clinical complications are often undetected and are not considered in the differential diagnosis. Convincing findings from studies suggest that HEV is clinically relevant not only in developing countries but also in industrialized countries. Eight HEV genotypes (HEV-1 to HEV-8) with different human and animal hosts and other HEV-related viruses are in circulation. Transmission routes vary by genotype and location, with large waterborne outbreaks in developing countries and zoonotic food-borne infections in developed countries. An acute infection can be aggravated in pregnant women, organ transplant recipients, patients with pre-existing liver disease and immunosuppressed patients. HEV during pregnancy affects the fetus and newborn with an increased risk of vertical transmission, preterm and stillbirth, neonatal jaundice and miscarriage. Hepatitis E is associated with extrahepatic manifestations that include neurological disorders such as neuralgic amyotrophy, Guillain-Barré syndrome and encephalitis, renal injury and haematological disorders. The risk of transfusion-transmitted HEV is increasingly recognized in Western countries where the risk may be because of a zoonosis. RNA testing of blood components is essential to determine the risk of transfusion-transmitted HEV. There are currently no approved drugs or vaccines for HEV infections. This review focuses on updating the latest developments in zoonoses, screening and diagnostics, drugs in use and under development, and vaccines.
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Affiliation(s)
- Thirumalaisamy P Velavan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Medical Research, VG-CARE, Hanoi, Vietnam
- Faculty of Medicine, Duy Tan University, Da Nang, Vietnam
| | - Srinivas R Pallerla
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Medical Research, VG-CARE, Hanoi, Vietnam
| | - Reimar Johne
- German Federal Institute for Risk Assessment, Berlin, Germany
| | - Daniel Todt
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
- European Virus Bioinformatics Center (EVBC), Jena, Germany
| | - Eike Steinmann
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
| | - Mathias Schemmerer
- Institute of Clinical Microbiology and Hygiene, National Consultant Laboratory for HAV and HEV, University Medical Center Regensburg, Regensburg, Germany
| | - Jürgen J Wenzel
- Institute of Clinical Microbiology and Hygiene, National Consultant Laboratory for HAV and HEV, University Medical Center Regensburg, Regensburg, Germany
| | - Jörg Hofmann
- Institute of Virology, Charité Universitätsmedizin Berlin, Labor Berlin-Charité-Vivantes GmbH, Berlin, Germany
| | | | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research, Partner Hannover-Braunschweig, Braunschweig, Germany
| | - Claus-Thomas Bock
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Division of Viral Gastroenteritis and Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
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23
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Al Absi ES, Al-Sadeq DW, Khalili M, Younes N, Al-Dewik N, Abdelghany SK, Abouzid SS, Al Thani AA, Yassine HM, Coyle PV, Nasrallah GK. The prevalence of HEV among non-A-C hepatitis in Qatar and efficiency of serological markers for the diagnosis of hepatitis E. BMC Gastroenterol 2021; 21:266. [PMID: 34130641 PMCID: PMC8207580 DOI: 10.1186/s12876-021-01841-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 06/08/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The rapid growth of Qatar in the last two decades has attracted a large influx of immigrant workers who mostly come from HEV-hyperendemic countries. Thus, we aim to investigate the prevalence of HEV among acute non-A-C hepatitis patients in Qatar; and to evaluate the performance of four dominant commercial serological assays for HEV diagnosis. METHODS 259 patients with non-A-C hepatitis were tested using the Wantai HEV-IgM, HEV-IgG, HEV-Ag ELISA kits, and the MP Biomedical HEV-Total Ab ELISA kit. ALT levels were tested and HEV RNA (viral loads) was performed using Taqman AmpliCube HEV RT-PCR kit (Mikrogen, Neuried, Germany). The performance of each kit was assessed according to the RT-PCR results. RESULTS HEV-RNA was detected in 23.1% of the samples. Most of these HEV-RNA-positive cases belonged to non-Qatari residents from the Indian subcontinent; India, Pakistan, etc. HEV-Ag, HEV-IgM, HEV-IgG, HEV-Total Ab were detected in 5.56%, 8.65%, 32.1%, and 34.2% of all tested samples, respectively. Elevated ALT levels were highly correlated with the HEV-Ag, HEV-IgM, HEV-RNA but not with the HEV-IgG and HEV-Total Ab. Although HEV-Ag was very specific (100%), yet its sensitivity was poor (36.7%). HEV-IgM demonstrated the best second marker for diagnosis of acute HEV after RT-PCR as jugged by the overall performance parameters: specificity (96.2%), sensitivity (71.4%), PPV (83.3%), NPP (92.7%), agreement with RT-PCR (91.0%), and Kappa-value (0.71). CONCLUSION Our study demonstrated a high prevalence of HEV virus in Qatar, mostly among immigrants from the Indian subcontinent. The HEV-IgM represents the best marker for detecting the acute HEV infection, where RT-PCR cannot be performed.
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Affiliation(s)
- Enas S Al Absi
- Biomedical Research Center, Qatar University, P.O. Box 2713, Doha, Qatar
| | - Duaa W Al-Sadeq
- Biomedical Research Center, Qatar University, P.O. Box 2713, Doha, Qatar
- College of Medicine, Member of QU Health, Qatar University, P.O. Box 2713, Doha, Qatar
| | - Makiyeh Khalili
- Department of Laboratory Medicine, Hamad Medical Corporation, Doha, Qatar
| | - Nadin Younes
- Biomedical Research Center, Qatar University, P.O. Box 2713, Doha, Qatar
| | - Nader Al-Dewik
- Clinical and Metabolic Genetics Section, Pediatrics Department, Hamad General Hospital, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
- Qatar Medical Genetic Center and Interim Translational Research Institute, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
- College of Health and Life Science, Hamad Bin Khalifa University, P.O. Box 34110, Doha, Qatar
- Department of Pediatrics, Women's Wellness and Research Center, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
| | - Sara K Abdelghany
- Department of Biomedical Science, College of Health Sciences, Member of QU Health, Qatar University, Women's Science Building, C01, P.O. Box 2713, Doha, Qatar
| | - Somaia S Abouzid
- Department of Biomedical Science, College of Health Sciences, Member of QU Health, Qatar University, Women's Science Building, C01, P.O. Box 2713, Doha, Qatar
| | - Asma A Al Thani
- Biomedical Research Center, Qatar University, P.O. Box 2713, Doha, Qatar
- Department of Biomedical Science, College of Health Sciences, Member of QU Health, Qatar University, Women's Science Building, C01, P.O. Box 2713, Doha, Qatar
| | - Hadi M Yassine
- Biomedical Research Center, Qatar University, P.O. Box 2713, Doha, Qatar
- Department of Biomedical Science, College of Health Sciences, Member of QU Health, Qatar University, Women's Science Building, C01, P.O. Box 2713, Doha, Qatar
| | - Peter V Coyle
- Virology Laboratory, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
| | - Gheyath K Nasrallah
- Biomedical Research Center, Qatar University, P.O. Box 2713, Doha, Qatar.
- Department of Biomedical Science, College of Health Sciences, Member of QU Health, Qatar University, Women's Science Building, C01, P.O. Box 2713, Doha, Qatar.
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Terrault NA, Levy MT, Cheung KW, Jourdain G. Viral hepatitis and pregnancy. Nat Rev Gastroenterol Hepatol 2021; 18:117-130. [PMID: 33046891 DOI: 10.1038/s41575-020-00361-w] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/21/2020] [Indexed: 02/06/2023]
Abstract
The management of viral hepatitis in the setting of pregnancy requires special consideration. There are five liver-specific viruses (hepatitis A, B, C, D, E), each with unique epidemiology, tendency to chronicity, risk of liver complications and response to antiviral therapies. In the setting of pregnancy, the liver health of the mother, the influence of pregnancy on the clinical course of the viral infection and the effect of the virus or liver disease on the developing infant must be considered. Although all hepatitis viruses can harm the mother and the child, the greatest risk to maternal health and subsequently the fetus is seen with acute hepatitis A virus or hepatitis E virus infection during pregnancy. By contrast, the primary risks for hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus are related to the severity of the underlying liver disease in the mother and the risk of mother-to-child transmission (MTCT) for HBV and HCV. The prevention of MTCT is key to reducing the global burden of chronic viral hepatitis, and prevention strategies must take into consideration local health-care and socioeconomic challenges. This Review presents the epidemiology of acute and chronic viral hepatitis infection in pregnancy, the effect of pregnancy on the course of viral infection and, conversely, the influence of the viral infection on maternal and infant outcomes, including MTCT.
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Affiliation(s)
- Norah A Terrault
- Keck School of Medicine, University of Southern California, Los Angeles, USA.
| | - Miriam T Levy
- Department of Gastroenterology and Liver, Liverpool Hospital, University of New South Wales, Sydney, New South Wales, Australia
| | - Ka Wang Cheung
- Department of Obstetrics and Gynaecology, Queen Mary Hospital, University of Hong Kong, Hong Kong, Hong Kong
| | - Gonzague Jourdain
- French National Research Institute for Sustainable Development (IRD), Marseille, France.,Chiang Mai University, Chiang Mai, Thailand
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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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Belei O, Ancusa O, Mara A, Olariu L, Amaricai E, Folescu R, Zamfir CL, Gurgus D, Motoc AG, Stânga LC, Strat L, Marginean O. Current Paradigm of Hepatitis E Virus Among Pediatric and Adult Patients. Front Pediatr 2021; 9:721918. [PMID: 34660485 PMCID: PMC8515027 DOI: 10.3389/fped.2021.721918] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 08/31/2021] [Indexed: 12/26/2022] Open
Abstract
Hepatitis E virus (HEV) infection is a polymorphic condition, present throughout the world and involving children and adults. Multiple studies over the last decade have contributed to a better understanding of the natural evolution of this infection in various population groups, several reservoirs and transmission routes being identified. To date, acute or chronic HEV-induced hepatitis has in some cases remained underdiagnosed due to the lower accuracy of serological tests and due to the evolutionary possibility with extrahepatic manifestations. Implementation of diagnostic tests based on nucleic acid analysis has increased the detection rate of this disease. The epidemiological and clinical features of HEV hepatitis differ depending on the geographical areas studied. HEV infection is usually a self-limiting condition in immunocompetent patients, but in certain categories of vulnerable patients it can induce a sudden evolution toward acute liver failure (pregnant women) or chronicity (immunosuppressed patients, post-transplant, hematological, or malignant diseases). In acute HEV infections in most cases supportive treatment is sufficient. In patients who develop chronic hepatitis with HEV, dose reduction of immunosuppressive medication should be the first therapeutic step, especially in patients with transplant. In case of unfavorable response, the initiation of antiviral therapy is recommended. In this review, the authors summarized the essential published data related to the epidemiological, clinical, paraclinical, and therapeutic aspects of HEV infection in adult and pediatric patients.
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Affiliation(s)
- Oana Belei
- First Pediatric Clinic, Disturbance of Growth and Development on Children Research Center, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Oana Ancusa
- Fifth Department of Internal Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Adelina Mara
- Department of Internal Medicine, Emergency City Hospital, Timisoara, Romania
| | - Laura Olariu
- First Pediatric Clinic, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Elena Amaricai
- Department of Rehabilitation Physical Medicine and Rheumatology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Roxana Folescu
- Department of Balneology, Medical Recovery and Rheumatology, Family Discipline, Center for Preventive Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Carmen Lacramioara Zamfir
- Department of Morpho-Functional Sciences I, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Daniela Gurgus
- Department of Balneology, Medical Recovery and Rheumatology, Family Discipline, Center for Preventive Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Andrei G Motoc
- Department of Anatomy and Embriology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Livia Claudia Stânga
- Department of Microbiology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Liliana Strat
- Department of Mother and Child Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Otilia Marginean
- First Pediatric Clinic, Disturbance of Growth and Development on Children Research Center, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
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Ngo DB, Chaibun T, Yin LS, Lertanantawong B, Surareungchai W. Electrochemical DNA detection of hepatitis E virus genotype 3 using PbS quantum dot labelling. Anal Bioanal Chem 2020; 413:1027-1037. [PMID: 33236225 DOI: 10.1007/s00216-020-03061-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 11/06/2020] [Accepted: 11/10/2020] [Indexed: 12/30/2022]
Abstract
The aim of this study was to develop a highly specific electrochemical DNA sensor using functionalized lead sulphide (PbS) quantum dots for hepatitis E virus genotype 3 (HEV3) DNA target detection. Functionalized-PbS quantum dots (QDs) were used as an electrochemical label for the detection of HEV3-DNA target by the technique of square wave anodic stripping voltammetry (SWASV). The functionalized-PbS quantum dots were characterized by UV-vis, FTIR, XRD, TEM and zeta potential techniques. As-prepared, functionalized-PbS quantum dots have an average size of 4.15 ± 1.35 nm. The detection platform exhibited LOD and LOQ values of 1.23 fM and 2.11 fM, respectively. HEV3-DNA target spiked serum is also reported.Graphical abstract.
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Affiliation(s)
- Duy Ba Ngo
- School of Bioresources and Technology, King Mongkut's University of Technology Thonburi (KMUTT), Bangkhuntien-Chaitalay Road, Bangkok, 10150, Thailand
| | - Thanyarat Chaibun
- Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Phutthamonthon, Nakhon Pathom, 73170, Thailand
| | - Lee Su Yin
- Department of Biotechnology, Faculty of Applied Sciences, AIMST University, Jalan, Bukit Air Nasi, 08100, Bedong, Kedah, Malaysia
| | - Benchaporn Lertanantawong
- Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Phutthamonthon, Nakhon Pathom, 73170, Thailand.
| | - Werasak Surareungchai
- School of Bioresources and Technology, King Mongkut's University of Technology Thonburi (KMUTT), Bangkhuntien-Chaitalay Road, Bangkok, 10150, Thailand. .,Nanoscience and Nanotechnology Graduate Program, Faculty of Science, King Mongkut's University of Technology Thonburi, Pracha Uthit Rd, Bangkok, 10140, Thailand.
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28
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Bagulo H, Majekodunmi AO, Welburn SC. Hepatitis E in Sub Saharan Africa - A significant emerging disease. One Health 2020; 11:100186. [PMID: 33204807 PMCID: PMC7653283 DOI: 10.1016/j.onehlt.2020.100186] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 10/09/2020] [Accepted: 10/17/2020] [Indexed: 12/17/2022] Open
Abstract
Hepatitis E is an emerging endemic disease found across the African continent, but there are clear differences in epidemiology between North Africa and countries south of the Sahara. In this systematic review, Google scholar and PubMed databases were searched for peer-reviewed articles on HEV epidemiology. Publications meeting our inclusion criteria were critically reviewed to extract consistent findings and identify knowledge gaps. Hepatitis E has been reported in 25 of the 49 countries in Sub Saharan Africa. Mortality rates of 1–2% in the general population and ~ 20% in pregnant women. Outbreaks were closely linked to refugees and Internally Displaced Persons in camps which accounted for 50% of reported outbreaks. There was very little research and concrete evidence for sources of contamination and transmission routes. There are indications of zoonotic transmission of Hepatitis E Virus infection but further research in these fields is required.
No data from 50% of African countries Outbreaks closely linked to refugee and IDP camps Little data on sources of HEV contamination Indications but little evidence of zoonotic transmission Low awareness amongst health professionals and general public
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Affiliation(s)
- Husein Bagulo
- Zhejiang University - University of Edinburgh Institute, Zhejiang University International Campus, 718 East Haizhou Rd, Haining, Zhejiang Province, 314400, China.,Livestock and Poultry Research Centre, College of Basic and Applied Sciences, University of Ghana, P. O Box LG 25, Legon, Accra, Ghana
| | - Ayodele O Majekodunmi
- Zhejiang University - University of Edinburgh Institute, Zhejiang University International Campus, 718 East Haizhou Rd, Haining, Zhejiang Province, 314400, China.,Livestock and Poultry Research Centre, College of Basic and Applied Sciences, University of Ghana, P. O Box LG 25, Legon, Accra, Ghana.,School of Biomedical Sciences, Edinburgh Medical School, College of Medicine & Veterinary Medicine, The University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, United Kingdom
| | - Susan C Welburn
- Zhejiang University - University of Edinburgh Institute, Zhejiang University International Campus, 718 East Haizhou Rd, Haining, Zhejiang Province, 314400, China.,School of Biomedical Sciences, Edinburgh Medical School, College of Medicine & Veterinary Medicine, The University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, United Kingdom
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29
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Ngamdee T, Yin LS, Vongpunsawad S, Poovorawan Y, Surareungchai W, Lertanantawong B. Target Induced-DNA strand displacement reaction using gold nanoparticle labeling for hepatitis E virus detection. Anal Chim Acta 2020; 1134:10-17. [PMID: 33059855 DOI: 10.1016/j.aca.2020.08.018] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 08/08/2020] [Accepted: 08/11/2020] [Indexed: 12/19/2022]
Abstract
DNA strand displacement is an attractive, enzyme-free target hybridization strategy for nano-biosensing. The target DNA induces a strand displacement reaction by replacing the pre-hybridized strand that is labeled with gold nanoparticles (AuNPs). Thus, the amount of displaced-AuNP-labeled strand is proportional to the amount of target DNA in the sample. The use of a magnetogenosensing technique to isolate the target DNA allows for a simple, one-pot detection approach, which minimizes possible carry-over contamination and pipetting errors. We sought a proof-of-concept for this technology in its ability to detect DNA-equivalent of hepatitis E virus (HEV), which causes acute viral hepatitis for which rapid and simple diagnostic methods remain limited. Signal detection was done via visual observation, spectrophotometry, and electrochemistry. The sensor demonstrated good sensitivity with detection limits of 10 pM (visual), 10 pM (spectrophotometry) and 1 fM (electrochemical). This sensor also exhibited high specificity for real target amplicons and could discriminate between perfect and mismatched sequences. Lyophilized biosensor reagents stored at 4 °C, 25 °C, and outdoor ambient temperature, were stable for up to 90, 50, and 40 days, respectively. The integration of magnetic separation and target DNA-induced strand displacement reaction in a dry reagent form makes the sensing platform easy-to-use and suitable for field settings.
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Affiliation(s)
- Tatchanun Ngamdee
- Department of Biotechnology, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, Bangkok, 10150, Thailand
| | - Lee Su Yin
- Faculty of Applied Sciences, AIMST University, Bedong, Kedah, 08100, Malaysia
| | - Sompong Vongpunsawad
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Werasak Surareungchai
- Department of Biotechnology, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, Bangkok, 10150, Thailand; Nanoscience and Nanotechnology Program, King Mongkut's University of Technology Thonburi (KMUTT), Bangkok, 10140, Thailand
| | - Benchaporn Lertanantawong
- Nanoscience and Nanotechnology Program, King Mongkut's University of Technology Thonburi (KMUTT), Bangkok, 10140, Thailand; Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Salaya, Nakhon Pathom, 73170, Thailand.
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30
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Lopes AM, Abrantes J. Hepatitis E virus is likely circulating in wild rabbits from Iberian Peninsula. Transbound Emerg Dis 2020; 67:1761-1763. [PMID: 32598572 DOI: 10.1111/tbed.13702] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 06/08/2020] [Indexed: 12/16/2022]
Affiliation(s)
- Ana M Lopes
- CIBIO-InBIO, Research Center in Biodiversity and Genetic Resources, University of Porto, Vairão, Portugal
| | - Joana Abrantes
- CIBIO-InBIO, Research Center in Biodiversity and Genetic Resources, University of Porto, Vairão, Portugal
- Department of Biology, Faculty of Sciences, University of Porto, Porto, Portugal
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31
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Kar P, Karna R. A Review of the Diagnosis and Management of Hepatitis E. CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES 2020; 12:310-320. [PMID: 32837339 PMCID: PMC7366488 DOI: 10.1007/s40506-020-00235-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Purpose of review We aim to provide the readers an up-to-date knowledge of the structure, epidemiology, and transmission followed by a detailed discussion on testing, diagnostics and management of hepatitis E virus infection. We have also included a comprehensive review of hepatitis E in pregnancy. Recent findings European Association for the Study of the Liver established clinical practice guidelines for testing and treatment of suspected hepatitis E virus infections in 2018. Evidence suggests chronic hepatitis E may follow a course similar to hepatitis B/C with progression to cirrhosis and possibly hepatocellular carcinoma in immunocompromised patients. Summary Hepatitis E virus is the most common cause of acute viral hepatitis worldwide. A combination of serology and nucleic acid amplification testing is the recommended strategy for suspected patients. Ribavirin therapy for a period of 3 months is the drug of choice for severe acute hepatitis, acute-on chronic liver failure, and chronic infections from hepatitis E virus in immunocompromised patients who are unresponsive to decreased immunosuppression. PEGylated interferon α can be used for ribavirin-resistant liver transplant patients with chronic hepatitis E. Further research in therapeutic options is essential considering the stormy course of hepatitis E infection during pregnancy and teratogenicity of all available options.
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Affiliation(s)
- P. Kar
- Department of Gastroenterology and Hepatology, Max Super Specialty Hospital,Ghaziabad, Delhi, New Delhi 110017 India
| | - R. Karna
- Maulana Azad Medical College & Lok Nayak Hospital, Bahadurshah Zafar Road, New Delhi, India
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Li P, Liu J, Li Y, Su J, Ma Z, Bramer WM, Cao W, de Man RA, Peppelenbosch MP, Pan Q. The global epidemiology of hepatitis E virus infection: A systematic review and meta-analysis. Liver Int 2020; 40:1516-1528. [PMID: 32281721 PMCID: PMC7384095 DOI: 10.1111/liv.14468] [Citation(s) in RCA: 147] [Impact Index Per Article: 29.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 03/29/2020] [Accepted: 04/01/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Hepatitis E virus (HEV), as an emerging zoonotic pathogen, is a leading cause of acute viral hepatitis worldwide, with a high risk of developing chronic infection in immunocompromised patients. However, the global epidemiology of HEV infection has not been comprehensively assessed. This study aims to map the global prevalence and identify the risk factors of HEV infection by performing a systematic review and meta-analysis. METHODS A systematic searching of articles published in Medline, Embase, Web of science, Cochrane and Google scholar databases till July 2019 was conducted to identify studies with HEV prevalence data. Pooled prevalence among different countries and continents was estimated. HEV IgG seroprevalence of subgroups was compared and risk factors for HEV infection were evaluated using odd ratios (OR). RESULTS We identified 419 related studies which comprised of 1 519 872 individuals. A total of 1 099 717 participants pooled from 287 studies of general population estimated a global anti-HEV IgG seroprevalence of 12.47% (95% CI 10.42-14.67; I2 = 100%). Notably, the use of ELISA kits from different manufacturers has a substantial impact on the global estimation of anti-HEV IgG seroprevalence. The pooled estimate of anti-HEV IgM seroprevalence based on 98 studies is 1.47% (95% CI 1.14-1.85; I2 = 99%). The overall estimate of HEV viral RNA-positive rate in general population is 0.20% (95% CI 0.15-0.25; I2 = 98%). Consumption of raw meat (P = .0001), exposure to soil (P < .0001), blood transfusion (P = .0138), travelling to endemic areas (P = .0244), contacting with dogs (P = .0416), living in rural areas (P = .0349) and receiving education less than elementary school (P < .0001) were identified as risk factors for anti-HEV IgG positivity. CONCLUSIONS Globally, approximately 939 million corresponding to 1 in 8 individuals have ever experienced HEV infection. 15-110 million individuals have recent or ongoing HEV infection. Our study highlights the substantial burden of HEV infection and calls for increasing routine screening and preventive measures.
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Affiliation(s)
- Pengfei Li
- Department of Gastroenterology and HepatologyErasmus MC‐University Medical CenterRotterdamThe Netherlands
| | - Jiaye Liu
- Department of Gastroenterology and HepatologyErasmus MC‐University Medical CenterRotterdamThe Netherlands
| | - Yang Li
- Department of Gastroenterology and HepatologyErasmus MC‐University Medical CenterRotterdamThe Netherlands
| | - Junhong Su
- Department of Gastroenterology and HepatologyErasmus MC‐University Medical CenterRotterdamThe Netherlands,Biomedical Research CenterNorthwest Minzu UniversityLanzhouChina
| | - Zhongren Ma
- Biomedical Research CenterNorthwest Minzu UniversityLanzhouChina
| | - Wichor M. Bramer
- Medical LibraryErasmus MC‐University Medical CenterRotterdamThe Netherlands
| | - Wanlu Cao
- Department of Gastroenterology and HepatologyErasmus MC‐University Medical CenterRotterdamThe Netherlands
| | - Robert A. de Man
- Department of Gastroenterology and HepatologyErasmus MC‐University Medical CenterRotterdamThe Netherlands
| | - Maikel P. Peppelenbosch
- Department of Gastroenterology and HepatologyErasmus MC‐University Medical CenterRotterdamThe Netherlands
| | - Qiuwei Pan
- Department of Gastroenterology and HepatologyErasmus MC‐University Medical CenterRotterdamThe Netherlands,Biomedical Research CenterNorthwest Minzu UniversityLanzhouChina
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Zaki MES, Alsayed MAL, Abbas HRR, Ahmed DM, Ashry AYE. Prevalence of hepatitis E virus in children with acute hepatitis: one Egyptian center study. Germs 2020; 10:88-94. [PMID: 32656105 PMCID: PMC7330519 DOI: 10.18683/germs.2020.1189] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 04/27/2020] [Accepted: 05/01/2020] [Indexed: 12/26/2022]
Abstract
INTRODUCTION The objective of the present study was to evaluate the prevalence of hepatitis E virus in acute hepatitis in pediatric patients. METHODS This was a cross-sectional study including 180 children with acute hepatitis. Blood samples were obtained and subjected to study the serological markers of hepatitis B surface antigen (HBsAg), hepatitis B core IgM (HBc IgM), hepatitis C IgG (HCV IgG) and hepatitis A IgM (HAV IgM), hepatitis E IgM and IgG, cytomegalovirus IgM (CMV IgM) and specific antibodies IgM for Epstein Barr virus by ELISA. Also ELISA attempted the laboratory diagnosis of autoantibodies by performing assay of antinuclear and anti-smooth muscle antibodies. Real time PCR was used for determination of HEV-RNA in samples positive for HEV serological markers. RESULTS From a total of 180 children with acute jaundice 69.4% were males and 39.6% were females with mean age ± standard deviation 5.8±3.5 years. Positive HEV markers were found in 47 patients (26.1%). A comparison between demographic, clinical and laboratory findings in children with positive HEV markers and children negative for HEV markers, revealed significant association with contact of animals (p=0.001), rural residence (p=0.001), presence of positive autoantibodies (p=0.001) and positive HAV IgM (p=0.001). The markers of hepatitis E virus showed significantly higher prevalence in children below age of 6 years (p=0.04). CONCLUSIONS HEV infection is more common in preschool age. There is a significant association between contact with animals, rural residence and other hepatitis affection like autoimmune hepatitis and other viral hepatitis viruses such as hepatitis A.
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Affiliation(s)
- Maysaa El Sayed Zaki
- MD, Clinical Pathology Department, Faculty of Medicine, Mansoura University, El Gomhoria street, Mansoura, Egypt
| | - Mona Abdel Latif Alsayed
- MD, Pediatric Medicine Department, Faculty of Medicine, Mansoura University, El Gomhoria Street, Mansoura, Egypt
| | - Hoda Ramadan Ryad Abbas
- Titles?, Medical Biochemistry Department, Faculty of Medicine, Beni-Suef University, Mohamed Hassan Street, Beni-Suef, Egypt
| | - Doaa Mabrouk Ahmed
- MD, Medical Microbiology and Immunology Department, Faculty of Medicine, Beni-Suef University, Mohamed Hassan Street, Beni-Suef, 6251, Egypt
| | - Amany Yusif El Ashry
- MD, Clinical Pathology Department, Faculty of Medicine, Mansoura University, El Gomhoria street, Mansoura, Egypt
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Nitta S, Takahashi K, Kawai-Kitahata F, Tsuchiya J, Sato A, Miyoshi M, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Kakinuma S, Watanabe M, Asahina Y. Time course alterations of virus sequences and immunoglobulin titers in a chronic hepatitis E patient. Hepatol Res 2020; 50:524-531. [PMID: 31883166 DOI: 10.1111/hepr.13480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Revised: 12/04/2019] [Accepted: 12/23/2019] [Indexed: 02/08/2023]
Abstract
AIM Hepatitis E virus (HEV) can cause chronic infection in immunocompromised hosts. However, the dynamics of HEV during persistent infection is not well understood. To elucidate time course alterations in virus sequences and anti-HEV antibodies during persistent infection, we analyzed the HEV sequences and titers of anti-HEV antibodies from a chronic hepatitis E patient. METHODS Serum samples were obtained from a chronic hepatitis E patient under corticosteroid therapy for neurological disease. The titers of anti-HEV antibodies (immunoglobulin A, immunoglobulin M, and immunoglobulin G) in serum samples were detected by enzyme immunoassay. The full or near-full nucleotide sequences of HEV isolated from consecutive serum samples were identified and compared. Phylogenetic analysis was also performed. RESULTS Alterations of anti-HEV antibodies from a chronic hepatitis E patient were different from those previously reported in acute hepatitis E patients. The virus sequence was unchanged in the period without treatment, but nucleotide mutations were observed after ribavirin treatment was started. In addition, the sequence of this strain had extremely high identity to that isolated from swine liver in Japan. CONCLUSIONS Virus mutations in HEV emerged after ribavirin treatment was started. Sequence analysis may useful for deciding the treatment strategy for chronic hepatitis E patients who did not eliminate the virus with 3 months of RBV treatment and inferring the origin of the infection. This report provides insights into the chronicity of hepatitis E, and the impact of persistent infection and ribavirin treatment on the emergence of virus mutations.
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Affiliation(s)
- Sayuri Nitta
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kazuaki Takahashi
- Department of Medical Sciences, Tokyo-Shinagawa Hospital, Tokyo, Japan.,Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Fukiko Kawai-Kitahata
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Jun Tsuchiya
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ayako Sato
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Masato Miyoshi
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Miyako Murakawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Itsui
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mina Nakagawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Seishin Azuma
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Sei Kakinuma
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,TMDU Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Asahina
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
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Hepatitis E Virus Infection in an Italian Cohort of Hematopoietic Stem Cell Transplantation Recipients: Seroprevalence and Infection. Biol Blood Marrow Transplant 2020; 26:1355-1362. [PMID: 32200124 DOI: 10.1016/j.bbmt.2020.03.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 01/15/2020] [Accepted: 03/10/2020] [Indexed: 01/05/2023]
Abstract
Chronic hepatitis E virus (HEV) infection in hematopoietic stem cell transplantation (HSCT) recipients is an emerging threat. The aim of this study was to provide data on the HEV burden in an Italian cohort of HSCT recipients and analyze risk factors for HEV seropositivity. This retrospective study reports data from 596 HSCT recipients compiled between 2010 and 2019. It included patients who underwent transplantation between 2010 and 2015 for whom pretransplantation (n = 419) and post-transplantation (n = 161) serum samples were available and tested retrospectively, as well as patients in whom prospective HEV testing was performed during the standard care: pre-HSCT IgG screening in 144, pre-HSCT HEV-RNA screening in addition to IgG screening in 60, and HEV-RNA testing in case of clinical suspicion of HEV infection in 59 (26 of whom were also included in the IgG screening cohorts). The rate of pre-HSCT HEV-IgG positivity was 6.0% (34 of 563). Older age was an independent risk factor for seropositivity (P = .039). None of the 34 HEV-IgG-positive patients had detectable HEV-RNA. One case of transient HEV-RNA positivity pre-HSCT was identified through screening. Two patients were diagnosed with chronic HEV hepatitis, and 1 patient was successfully treated with ribavirin. The burden of HEV infection in HSCT recipients in Italy is limited, and pre-HSCT screening appears to be of no benefit. Timely diagnosis of HEV infection with HEV-RNA is mandatory in cases of clinical suspicion.
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36
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Mikolajczyk AE, Chung NL. Diagnostic Testing for Acute Hepatitis. JAMA 2020; 323:992-993. [PMID: 32053136 DOI: 10.1001/jama.2019.21895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Affiliation(s)
- Adam E Mikolajczyk
- Division of Gastroenterology and Hepatology, University of Illinois at Chicago, Chicago, Illinois
| | - Nakia L Chung
- Department of Internal Medicine, University of Illinois at Chicago, Chicago, Illinois
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37
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Llovet LP, Gratacós-Ginés J, Ortiz O, Rodriguez-Tajes S, Lens S, Reverter E, Ruiz-Ortiz E, Costa J, Viñas O, Forns X, Parés A, Londoño MC. Higher seroprevalence of hepatitis E virus in autoimmune hepatitis: Role of false-positive antibodies. Liver Int 2020; 40:558-564. [PMID: 31863722 DOI: 10.1111/liv.14332] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Revised: 12/01/2019] [Accepted: 12/15/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Recent studies have found an increase in the seroprevalence of hepatitis E virus (HEV) infection in patients with autoimmune hepatitis (AIH). We aimed to assess the prevalence of positive anti-HEV IgM and IgG, and HEV-RNA in a cohort of patients with AIH, to determine the impact of positive HEV serology on patient outcome, and to evaluate the role of hypergammaglobulinemia and positive autoantibodies in the presence of positive anti-HEV serology. METHODS One hundred and five patients tested for HEV infection between 2014 and 2018 were included in the study: 50 with chronic AIH (more than 1 year on treatment), and 55 with an acute hepatitis (30 patients with acute AIH and 25 with non-AIH). RESULTS Seroprevalence of HEV was higher in patients with acute AIH (17% vs 10% in patients with chronic AIH and 8% in patients with non-AIH). Patients with acute AIH and positive anti-HEV IgG were older (58 vs 40; P = .006), had higher IgG levels (27 g/dL vs 13 g/dL; P = .03) and antismooth muscle antibodies (ASMA) titres (1:160 vs 1:80; P = .045), and were more likely to have another autoimmune disease (60% vs 16%; P = .03). At the time of HEV testing, anti-HEV IgG positive patients had significantly higher serum IgG levels (17 g/L vs 11 g/L; P = .009), ANA (1:160 vs 1:60; P = .026) and ASMA titres (1:80 vs 1:40; P = .021). CONCLUSION Seroprevalence of HEV in patients with AIH in Catalonia does not differ from that of the general population. The higher HEV seroprevalence in patients with acute AIH with higher levels of gammaglobulins and high antibody titres suggest the presence of cross-reactivity between HEV and liver antigens.
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Affiliation(s)
| | | | - Oswaldo Ortiz
- Liver Unit, Hospital Clinic Barcelona, CIBERehd, IDIBAPS, Barcelona, Spain
| | | | - Sabela Lens
- Liver Unit, Hospital Clinic Barcelona, CIBERehd, IDIBAPS, Barcelona, Spain
| | - Enric Reverter
- Liver Unit, Hospital Clinic Barcelona, CIBERehd, IDIBAPS, Barcelona, Spain
| | - Estibaliz Ruiz-Ortiz
- Immunology Department, Centre Diagnòstic Biomèdic, Hospital Clínic Barcelona, IDIBAPS, Barcelona, Spain
| | - Josep Costa
- Microbiology Service, Hospital Clinic, University of Barcelona, CIBERehd, IDIBAPS, Barcelona, Spain
| | - Odette Viñas
- Immunology Department, Centre Diagnòstic Biomèdic, Hospital Clínic Barcelona, IDIBAPS, Barcelona, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clinic Barcelona, CIBERehd, IDIBAPS, Barcelona, Spain
| | - Albert Parés
- Liver Unit, Hospital Clinic Barcelona, CIBERehd, IDIBAPS, Barcelona, Spain
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Choi Y, Zhang X, Skinner B. Analysis of IgG Anti-HEV Antibody Protective Levels During Hepatitis E Virus Reinfection in Experimentally Infected Rhesus Macaques. J Infect Dis 2020; 219:916-924. [PMID: 30325442 DOI: 10.1093/infdis/jiy603] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Accepted: 10/10/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Secondary spread of hepatitis E virus (HEV) infection occurs often in endemic settings in developing countries. The host immune signatures contributing to protection against subsequent HEV reinfection are unknown. METHODS Twelve seroconverted rhesus macaques were reinoculated with homologous HEV genotype 1 (gt1, Sar-55) and followed for 115 days. HEV RNA, HEV-specific T-cell responses, IgG anti-HEV antibody, and the IgG anti-HEV avidity index were tested. RESULTS Four animals with baseline IgG anti-HEV levels from 1.5 to 13.4 World Health Organization (WHO) U/mL evidenced reinfection as determined by HEV RNA in stool, and increase in IgG anti-HEV levels between 63- and 285-fold (P = .003). Eight animals with baseline IgG anti-HEV levels from 2.8 to 90.7 WHO U/mL did not develop infection or shed virus in feces, and IgG anti-HEV antibody levels were unchanged (P = .017). The 4 reinfected animals showed a lower HEV-IgG avidity index (average 35.5%) than the 8 protected animals (average 62.1%). HEV-specific interferon-gamma-producing T cells were 2-fold higher in reinfected animals (P = .018). CONCLUSIONS Preexisting antibody and high IgG avidity index (>50%) are important factors for protection against HEV reinfection. HEV-specific T-cell responses were elevated in reinfected animals after subsequent exposure to HEV.
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Affiliation(s)
- Youkyung Choi
- Laboratory Branch, Division of Viral Hepatitis, National Centers for HIV/AIDS, Viral Hepatitis, STD, and TB prevention
| | - Xiugen Zhang
- Laboratory Branch, Division of Viral Hepatitis, National Centers for HIV/AIDS, Viral Hepatitis, STD, and TB prevention
| | - Brianna Skinner
- Comparative Medicine Branch, Division of Scientific Resources, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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Chauhan A, Webb G, Ferguson J. Clinical presentations of Hepatitis E: A clinical review with representative case histories. Clin Res Hepatol Gastroenterol 2019; 43:649-657. [PMID: 30808575 PMCID: PMC6864596 DOI: 10.1016/j.clinre.2019.01.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Revised: 01/03/2019] [Accepted: 01/21/2019] [Indexed: 02/04/2023]
Abstract
Hepatitis E virus (HEV) typically causes an acute, self-limiting hepatitis and is among the commonest cause of such presentations. Hepatitis E viral infection is also increasingly recognized as a cause of chronic hepatitis amongst the immunocompromised, particularly amongst solid organ transplant recipients. Chronic HEV infection remains an underdiagnosed disease and chronic infection can lead to rapidly progressive liver fibrosis and cirrhosis. This review examines current understanding of the HEV. We illustrate typical clinical presentations, management strategies [(based upon guidelines from both the British Transplant Society (BTS) and European Association for the study of liver (EASL)] and outcomes of HEV infection in different cohorts of patients by highlighting select transplant and non-transplant patient cases, from one of the largest tertiary Hepatology centres in Europe.
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Affiliation(s)
- Abhishek Chauhan
- NIHR Birmingham Biomedical Research Centre, United Kingdom; Liver unit, University Hospitals Birmingham, United Kingdom; Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom.
| | - Gwilym Webb
- Liver unit, University Hospitals Birmingham, United Kingdom; Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom
| | - James Ferguson
- Liver unit, University Hospitals Birmingham, United Kingdom
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40
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41
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Fernandez-Flores A. La biopsia cutánea en el contexto de la enfermedad sistémica. ACTAS DERMO-SIFILIOGRAFICAS 2019; 110:710-727. [DOI: 10.1016/j.ad.2019.02.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 02/11/2019] [Accepted: 02/12/2019] [Indexed: 02/07/2023] Open
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Fousekis FS, Mitselos IV, Christodoulou DK. Extrahepatic manifestations of hepatitis E virus: An overview. Clin Mol Hepatol 2019; 26:16-23. [PMID: 31601068 PMCID: PMC6940480 DOI: 10.3350/cmh.2019.0082] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 09/16/2019] [Indexed: 12/14/2022] Open
Abstract
Hepatitis E virus (HEV) is a significant health problem with approximately 20 million individuals infected annually. HEV infection has been associated with a wide spectrum of extrahepatic manifestations, including neurological, hematological and renal disorders. Guillain-Barré syndrome and neuralgic amyotrophy are the most frequent neurological manifestations. In addition, HEV infection has been observed with other neurological diseases, such as encephalitis, myelitis and Bell’s palsy. Hematologic manifestations include anemia due to glucose-6-phospate dehydrogonase deficiency, autoimmune hemolytic anemia and severe thrombocytopenia. Membranoproliferative glomerulonephritis and relapse IgA nephropathy with or without coexisting cryoglobulinemia appear to be the most common renal injuries related with HEV infection. Also, HEV infection has been associated with acute pancreatitis and other immune-mediated manifestations, such as arthritis and myocarditis. However, the pathophysiologic mechanisms of HEV-related extrahepatic manifestations are still largely unclear.
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Affiliation(s)
- Fotios S Fousekis
- Department of Gastroenterology and Hepatology, University Hospital of Ioannina, School of Health Sciences, University of Ioannina, Ioannina, Greece
| | - Ioannis V Mitselos
- Department of Gastroenterology and Hepatology, University Hospital of Ioannina, School of Health Sciences, University of Ioannina, Ioannina, Greece
| | - Dimitrios K Christodoulou
- Department of Gastroenterology and Hepatology, University Hospital of Ioannina, School of Health Sciences, University of Ioannina, Ioannina, Greece
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Rivero-Juarez A, Lopez-Lopez P, Frias M, Rivero A. Hepatitis E Infection in HIV-Infected Patients. Front Microbiol 2019; 10:1425. [PMID: 31297100 PMCID: PMC6608679 DOI: 10.3389/fmicb.2019.01425] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 06/05/2019] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND The hepatitis E virus (HEV) represents a major cause of acute hepatitis worldwide. The majority of HEV cases occur in low-income countries, mainly Asia and Africa, where HEV causes large outbreaks associated with the consumption of contaminated water and high mortality in specific populations. In high-income countries, HEV infection is considered a zoonotic disease that is linked to the consumption of contaminated food. Although a high proportion of cases have self-limiting asymptomatic or subclinical infections, immunosuppression may modify the pathogenesis and clinical impact of this emerging disease. RESULTS AND DISCUSSION Here, we review the current knowledge about the epidemiology, diagnosis, clinical manifestations, management and prevention of HEV infection in HIV-infected subjects. CONCLUSIONS Despite the increasing knowledge about the pathogenesis, epidemiology and clinical impact of HEV infection, several major factors are faced by HIV-infected patients, including treatment recommendations, immunization and risk practices.
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Affiliation(s)
- Antonio Rivero-Juarez
- Infectious Diseases Unit, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía de Córdoba, Universidad de Córdoba, Córdoba, Spain
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Pathogenic mechanisms and current epidemiological status of HEV infection in asymptomatic blood donors and patients with chronic diseases. Eur J Clin Microbiol Infect Dis 2019; 38:1203-1209. [PMID: 30888550 DOI: 10.1007/s10096-019-03534-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 03/08/2019] [Indexed: 12/15/2022]
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Vázquez-Morón S, Berenguer J, González-García J, Jiménez-Sousa MÁ, Canorea I, Guardiola JM, Crespo M, Quereda C, Sanz J, Carrero A, Hontañón V, Avellón A, Resino S. Prevalence of hepatitis E infection in HIV/HCV-coinfected patients in Spain (2012-2014). Sci Rep 2019; 9:1143. [PMID: 30718554 PMCID: PMC6361883 DOI: 10.1038/s41598-018-37328-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Accepted: 11/27/2018] [Indexed: 12/14/2022] Open
Abstract
Hepatitis E virus (HEV) has emerged as a relevant pathogen for HIV-infected patients. However, there is scarce data on HEV infection in HIV/HCV-coinfected individuals with advanced fibrosis, which seems to increase the risk of HEV infection and worsen the prognosis of liver disease. We aimed to determine the prevalence of anti-HEV antibodies, acute hepatitis E, resolved hepatitis E, and exposure to HEV in HIV/HCV-coinfected patients and to evaluate associations with clinical and epidemiological characteristics. We performed a cross-sectional study on 198 HIV/HCV-coinfected patients, 30 healthy controls and 36 HIV-monoinfected patients. We found a low concordance between techniques used for detection of anti-HEV antibodies (ELISA versus Immunoblot), particularly in HIV/HCV-coinfected patients. HIV/HCV-coinfected patients showed the highest prevalence of IgG against HEV, resolved hepatitis E, and exposure to HEV (19.2%, 17.2%, and 22.2% respectively). However, we did not find any samples positive for HEV-RNA nor significant differences between groups. Moreover, HIV/HCV-coinfected patients with CD4 T-cells <350 cells/mm3 had higher prevalence for anti-HEV IgG antibodies, resolved hepatitis E, and exposure to HEV than healthy controls or those with CD4 T-cells ≥ 350 cells/mm3 (p = 0.034, p = 0.035, and p = 0.053; respectively). In conclusion, HIV/HCV-coinfected patients in Spain have a high prevalence for IgG anti-HEV antibodies, resolved hepatitis E, and exposure to HEV; particularly patients with CD4+T-cells <350 cells/mm3.
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Affiliation(s)
- Sonia Vázquez-Morón
- Laboratorio de Referencia e Investigación en Hepatitis Víricas, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
| | - Juan Berenguer
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.,Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain
| | - Juan González-García
- Unidad de VIH, Servicio de Medicina Interna, Hospital Universitario "La Paz"/IdiPAZ, Madrid, Spain
| | - Ma Ángeles Jiménez-Sousa
- Laboratorio de Referencia e Investigación en Hepatitis Víricas, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Isabel Canorea
- Laboratorio de Referencia e Investigación en Hepatitis Víricas, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | | | - Manuel Crespo
- Complexo Hospitalario Universitario, Fundación IIS Galicia Sur, Vigo, Pontevedra, Spain
| | | | - José Sanz
- Hospital Universitario Príncipe de Asturias. Alcalá de Henares, Madrid, Spain
| | - Ana Carrero
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.,Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain
| | - Victor Hontañón
- Unidad de VIH, Servicio de Medicina Interna, Hospital Universitario "La Paz"/IdiPAZ, Madrid, Spain
| | - Ana Avellón
- Laboratorio de Referencia e Investigación en Hepatitis Víricas, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Salvador Resino
- Laboratorio de Referencia e Investigación en Hepatitis Víricas, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
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Horn J, Hoodgarzadeh M, Klett-Tammen CJ, Mikolajczyk RT, Krause G, Ott JJ. Epidemiologic estimates of hepatitis E virus infection in European countries. J Infect 2018; 77:544-552. [DOI: 10.1016/j.jinf.2018.09.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Accepted: 09/20/2018] [Indexed: 12/16/2022]
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Mohd Hanafiah K, Garcia ML, Barnes NC, Anderson DA. Detection of virus-specific polymeric immunoglobulin A in acute hepatitis A, C, E virus serum samples using novel chimeric secretory component. BMC Res Notes 2018; 11:688. [PMID: 30285838 PMCID: PMC6167832 DOI: 10.1186/s13104-018-3799-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Accepted: 09/27/2018] [Indexed: 01/23/2023] Open
Abstract
Objective To conduct a proof-of-concept study on preferential binding of polymeric IgA (pIgA) using a novel recombinant rabbit/human chimeric secretory component (cSC) and preliminary assessment of the diagnostic potential of virus-specific pIgA in discriminating acute hepatitis A, E, and C (HAV, HEV, HCV) patients and uninfected controls using an indirect enzyme-linked immunoassay. Results cSC binds > 0.06 μg/ml of purified human and mouse pIgA with negligible cross-reactivity against IgM and IgA. Virus-specific pIgA was significantly higher in serum of acute HAV (n = 6) and HEV (n = 12) patients than uninfected samples (HEV: p < 0.001; HAV: p = 0.001), and had low correlation with virus-specific IgM (HEV r: − 0.25, 95% CI − 0.88 to 0.71, p = 0.636; HAV r: 0.05, 95% CI − 0.54 to 0.60, p: 0.885). Anti-HCV pIgA peaked early in HCV seroconversion panels (n = 14), and was undetectable after 4 weeks post-primary bleed, even in ongoing infections, while serum anti-HCV IgA, IgG and IgM persisted. Patients with early acute HCV infection had significantly higher levels of anti-HCV pIgA compared to those with chronic infections (p < 0.01). The use of novel cSC demonstrates the presence of virus-specific pIgA in sera of patients with acute HAV, HEV, and HCV infection, and posits its potential utility as a diagnostic biomarker that warrants further validation on larger sample populations.
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Affiliation(s)
- Khayriyyah Mohd Hanafiah
- Life Sciences, Macfarlane Burnet Institute, 85 Commercial Rd, Melbourne, VIC, 3004, Australia. .,Department of Immunology, Monash University, 86 Commercial Road, Melbourne, VIC, 3004, Australia. .,School of Biological Sciences, Universiti Sains Malaysia, Gelugor, Penang, 11800, Malaysia.
| | - Mary L Garcia
- Life Sciences, Macfarlane Burnet Institute, 85 Commercial Rd, Melbourne, VIC, 3004, Australia
| | - Nadine C Barnes
- Life Sciences, Macfarlane Burnet Institute, 85 Commercial Rd, Melbourne, VIC, 3004, Australia
| | - David A Anderson
- Life Sciences, Macfarlane Burnet Institute, 85 Commercial Rd, Melbourne, VIC, 3004, Australia.,Department of Microbiology and Immunology, University of Melbourne, 792 Elizabeth Street, Melbourne, VIC, 3000, Australia
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Al-Absi ES, Al- Sadeq DW, Younis MH, Yassine HM, Abdalla OM, Mesleh AG, Hadwan TA, Amimo JO, Thalib L, Nasrallah GK. Performance evaluation of five commercial assays in assessing seroprevalence of HEV antibodies among blood donors. J Med Microbiol 2018; 67:1302-1309. [DOI: 10.1099/jmm.0.000807] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Enas S. Al-Absi
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
- 2Biomedical Research Center, Qatar University, Doha, Qatar
| | - Duaa W. Al- Sadeq
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Manaf H. Younis
- 3Department of Public Health, College of Health Sciences, Qatar University, Doha, Qatar
| | | | - Omnya M. Abdalla
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Areej G. Mesleh
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Tameem A. Hadwan
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Joshua O. Amimo
- 4Department of Animal Production, Faculty of Veterinary Medicine University of Nairobi, Nairobi, Kenya
- 5Bioscieces of Eastern and Central Africa-International Livestock Research Institute (BecA-ILRI), Nairobi, Kenya
| | - Lukman Thalib
- 5Bioscieces of Eastern and Central Africa-International Livestock Research Institute (BecA-ILRI), Nairobi, Kenya
| | - Gheyath K. Nasrallah
- 1Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
- 2Biomedical Research Center, Qatar University, Doha, Qatar
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Hepatitis E virus infection in Turkey: a systematic review. Ann Clin Microbiol Antimicrob 2018; 17:17. [PMID: 29716597 PMCID: PMC5930810 DOI: 10.1186/s12941-018-0269-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Accepted: 04/23/2018] [Indexed: 01/05/2023] Open
Abstract
Hepatitis E virus (HEV), a non-enveloped single stranded RNA virus causes sporadic cases of hepatitis or outbreaks. The disease is generally self-limited although it may cause fulminant hepatitis in pregnant women, elderly, those with underlying chronic hepatitis, immunosuppressed, and transplant recipients. It is transmitted through fecal–oral route and zoonotic transmission. Hepatitis is a main health care problem in Turkey; HBV and HCV prevalences are 4 and 1% respectively. Hepatitis D represents another considerable hepatitis etiology with a prevalence of 5–27%. The information about HEV is not clear. In this systematic review, we aimed to analyze HEV studies reported from Turkey, to determine the current situation of the disease in the country, to delineate the limits of the studies and to determine the future study areas. The prevalence of HEV ranged from 0 to 12.4%. Children had lower prevalence than the adults. The prevalence was determined as 7–8% in pregnant women, 13% in chronic HBV patients, 54% in chronic HCV patients, 13.9–20.6% in patients with chronic renal failure, and ≈ 35% in agriculture workers. Among individuals immigrating form Turkey to Europe, HEV seroprevalence was found 10.3% in Italy and 33.4% in the Netherlands. HEV prevalence seems high in certain risk groups. Although previous studies suggest that Turkey is among the endemic countries of HEV, there are some pitfalls for the analysis of data: the studies are not powered enough to represent the whole population; they did not include immunosuppressed patients and solid organ recipients; and the prevalence of non-A non-B hepatitis was not determined.
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