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Zhang L, Zhang Q, Liu J, Wu W, Jiang Z, Yan B, Cao Q, Liu H, Pan H, Lv J, Feng Y, Xu F, Huang S, Xu A. Immunogenicity and safety of HepE Hecolin® in chronic hepatitis B patients at clinically stable stage: An open-label study in China. Hum Vaccin Immunother 2025; 21:2448882. [PMID: 39797410 PMCID: PMC11730616 DOI: 10.1080/21645515.2024.2448882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 12/24/2024] [Accepted: 12/28/2024] [Indexed: 01/15/2025] Open
Abstract
Acute hepatitis E infection could induce severe outcomes among chronic hepatitis B (CHB) patients. Between 2016 and 2017, an open-label study was conducted to evaluate the immunogenicity and safety of hepatitis E vaccine (HepE) in CHB patients, using healthy adults as parallel controls in China. Eligible participants who were aged ≥30 y were enrolled in the study. The CHB group included participants who had ever developed symptoms of hepatitis because of CHB but was currently at a clinically stable stage, which was defined as ALT ≤ 1.5 times of upper limit of the normal range (ULN) in this study. The control group included healthy adults who had hepatitis B surface antigen (HBsAg) negative. HepE was administered for 0, 1, 6 months for all participants. At 1 month after the third-dose vaccination (month 7), the seroconversion rates of anti-HEV IgG were >97% in both groups. The geometric mean concentration (GMC) of anti-HEV IgG in the CHB group was non-inferior to the healthy adult group (0.69 WU/mL, 95% CI 0.55-0.85). The proportion of the participants with adverse events ≥ grade 3 was similar in both groups (p = .99), and no vaccine-associated severe adverse events were identified. Changes in the liver function indicators were not of clinical significance. The HepE was highly immunogenic and well tolerated among clinically stable CHB patients and healthy adults.
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Affiliation(s)
- Li Zhang
- Academy of Preventive Medicine, Shandong University, Jinan, China
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China
| | - Qiufen Zhang
- Department of Medicine, Xiamen Innovax Biotech Co. Ltd, Xiamen, China
| | - Jiaye Liu
- School of Public Health, Shenzhen University Medical School, Shenzhen, China
| | - Wenlong Wu
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China
| | - Zechun Jiang
- Division of Expanded Program Immunization, Rushan Center for Disease Control and Prevention, Rushan, China
| | - Bingyu Yan
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China
| | - Qingfan Cao
- Division of Expanded Program Immunization, Rushan Center for Disease Control and Prevention, Rushan, China
| | - Haidong Liu
- Division of Expanded Program Immunization, Rushan Center for Disease Control and Prevention, Rushan, China
| | - Huirong Pan
- Department of Medicine, Xiamen Innovax Biotech Co. Ltd, Xiamen, China
| | - Jingjing Lv
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China
| | - Yi Feng
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China
| | - Fujie Xu
- Global Health Research Center, Duke Kunshan University, Kunshan, China
| | - Shoujie Huang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Strait Collaborative Innovation Center of Biomedicine and Pharmaceutics, School of Public Health, Xiamen University, China
| | - Aiqiang Xu
- Academy of Preventive Medicine, Shandong University, Jinan, China
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China
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Zhuang C, Liu X, Huang X, Lu J, Zhu K, Liao M, Chen L, Jiang H, Zang X, Wang Y, Yang C, Liu D, Zheng Z, Zhang X, Huang S, Huang Y, Su Y, Wu T, Zhang J, Xia N. Effectiveness of a hepatitis E vaccine against medically-attended symptomatic infection in HBsAg-positive adults from a test-negative design study. Nat Commun 2025; 16:1699. [PMID: 39962038 PMCID: PMC11832733 DOI: 10.1038/s41467-025-57021-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Accepted: 02/08/2025] [Indexed: 02/20/2025] Open
Abstract
The effectiveness of the hepatitis E vaccine in high-risk groups, such as chronic hepatitis B (CHB) patients, remains understudied. A key clinical manifestation of CHB is the persistent positivity of hepatitis B surface antigen (HBsAg). We conducted a test-negative design study involving 2,926 HBsAg-positive individuals (born 1941-1991; median age 49.0; male-to-female ratio of 1.4), identified through a hepatitis surveillance system, as part of the phase 3 trial (NCT01014845) of the recombinant hepatitis E vaccine HEV 239 (Hecolin). This system monitored suspected hepatitis cases and performed diagnoses across 11 townships in Dongtai, Jiangsu, China, from 2007 to 2017. Vaccine effectiveness of HEV 239 was assessed by comparing vaccination status between confirmed 96 hepatitis E cases and 2830 test-negative controls, using logistic regression adjusted for sex and age. We found that HEV 239 vaccination was associated with a reduced risk of hepatitis E among HBsAg-positive individuals, with an estimated effectiveness of 72.1% [95% confidence interval (CI) 11.2-91.2], and 81.5% (95% CI 35.9-94.6) among phase 3 trial participants. Our findings show that HEV 239 is highly effective in HBsAg-positive adults, supporting its future recommended use in this population.
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Affiliation(s)
- Chunlan Zhuang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, China
| | - Xiaohui Liu
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, China
| | - Xingcheng Huang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, China
| | - Jiaoxi Lu
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, China
| | - Kongxin Zhu
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, China
| | - Mengjun Liao
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, China
| | - Lu Chen
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, China
| | - Hanmin Jiang
- Dongtai Centre for Disease Control and Prevention, Yancheng, Jiangsu, China
| | - Xia Zang
- Dongtai Centre for Disease Control and Prevention, Yancheng, Jiangsu, China
| | - Yijun Wang
- Dongtai Centre for Disease Control and Prevention, Yancheng, Jiangsu, China
| | - Changlin Yang
- Dongtai Centre for Disease Control and Prevention, Yancheng, Jiangsu, China
| | - Donglin Liu
- Dongtai Centre for Disease Control and Prevention, Yancheng, Jiangsu, China
| | - Zizheng Zheng
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, China
| | - Xuefeng Zhang
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China
| | - Shoujie Huang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, China
| | - Yue Huang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China.
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, China.
| | - Yingying Su
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China.
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, China.
| | - Ting Wu
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, China
| | - Jun Zhang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China.
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, China.
| | - Ningshao Xia
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, China
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Buti M, Ruiz-Cobo JC, Esteban R, Riveiro-Barciela M. Hepatitis E as a trigger for acute-on-chronic liver failure. Clin Mol Hepatol 2025; 31:S196-S204. [PMID: 39523715 PMCID: PMC11925444 DOI: 10.3350/cmh.2024.0758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/27/2024] [Accepted: 11/07/2024] [Indexed: 11/16/2024] Open
Abstract
Acute hepatitis E virus (HEV) infection is typically self-limiting and has a favourable prognosis. However, certain populations such as patients with pre-existing chronic liver disease may experience severe manifestations, including progression to acute-on-chronic liver failure (ACLF). Among viral hepatitis types, hepatitis A, E, and B are major causes of ACLF. Active screening and early diagnosis of HEV infection in patients with cirrhosis, especially those who develop ACLF, can improve management and enable timely antiviral therapy. Preventive measures, including HEV vaccination for high-risk groups, could reduce the morbidity and mortality associated with hepatitis E.
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Affiliation(s)
- Maria Buti
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Juan Carlos Ruiz-Cobo
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Rafael Esteban
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Mar Riveiro-Barciela
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER)
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Wang F, Zhou L, Wagner AL, Chen Z, Lu Y. Cost-Effectiveness of Hepatitis E Vaccination Strategies among Patients with Chronic Liver Diseases in China: A Model-Based Evaluation. Vaccines (Basel) 2024; 12:1101. [PMID: 39460268 PMCID: PMC11511531 DOI: 10.3390/vaccines12101101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 09/24/2024] [Accepted: 09/25/2024] [Indexed: 10/28/2024] Open
Abstract
Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis worldwide, primarily transmitted through contaminated water and food. In patients with chronic liver disease (CLD), HEV infection might worsen the prognosis. This study aimed to evaluate the cost-effectiveness of hepatitis E vaccination strategies in CLD patients. A decision tree-Markov cohort model was used to assess the cost-effectiveness of universal-vaccination, vaccination-following-screening, and no-vaccination strategies in 100,000 CLD patients over their lifetimes, simulating cohorts aged ≥16 years, ≥40 years, and ≥60 years, based on the licensed vaccination ages and typical ages of CLD onset, from a societal perspective. Model parameters were retrieved and estimated from previous publications and government data. The outcomes included HEV-related cases, costs, and the incremental cost-effectiveness ratio (ICER). Compared to no-vaccination, universal-vaccination reduced HEV-related cases by 32.8% to 39.6%, while vaccination-following-screening reduced them by 38.1% to 49.3%. Furthermore, universal-vaccination showed ICERs of USD 6898.33, USD 6638.91, and USD 6582.69 per quality-adjusted life year (QALY) for cohorts aged ≥16, ≥40, and ≥60 years, respectively. Moreover, the vaccination-following-screening strategy significantly enhanced cost-effectiveness, with ICERs decreasing to USD 6201.55, USD 5199.46, and USD 4919.87 per QALY for the cohorts. Additionally, one-way sensitivity analysis identified the discount rate and utility for CLD patients as the key factors influencing ICER. Probabilistic sensitivity analysis indicated the vaccination-following-screening strategy was cost-effective with probabilities of 92.50%, 95.70%, and 95.90% for each cohort. Hepatitis E vaccination in CLD patients costs less than GDP per capita for each QALY gained in China. The vaccination-following-screening strategy may be the optimal option, especially in those over 60 years.
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Affiliation(s)
- Fengge Wang
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China; (F.W.); (Z.C.)
- Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai 200032, China;
| | - Lu Zhou
- Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai 200032, China;
| | - Abram L. Wagner
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA;
- Global Institute for Vaccine Equity, University of Michigan, Ann Arbor, MI 48109, USA
| | - Zixiang Chen
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China; (F.W.); (Z.C.)
- Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai 200032, China;
| | - Yihan Lu
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China; (F.W.); (Z.C.)
- Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai 200032, China;
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Olariu MC, Filipescu MC, Pauna AM, Simoiu M, Borcan AM. HEV Infection in the Context of Prior HBV-Related Liver Injury: Case Series. Infect Dis Rep 2024; 16:888-893. [PMID: 39311211 PMCID: PMC11417802 DOI: 10.3390/idr16050070] [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: 08/02/2024] [Revised: 09/02/2024] [Accepted: 09/04/2024] [Indexed: 09/26/2024] Open
Abstract
Hepatitis E virus (HEV) is a common cause of acute hepatitis, with increasing incidence in Europe, including Romania. Concurrently, Romania has a high prevalence of chronic hepatitis B (CHB). There is limited research on the clinical presentation and outcomes of HEV infection in patients with pre-existing chronic hepatitis B (CHB), especially in resource-rich settings. Most literature data come from South, East, and Southeast Asia. A review of the literature on HEV and HBV co-infection indicates a severe prognosis, particularly in patients with underlying liver disease. However, the cases in this study, which did not display cirrhosis, showed varied outcomes. The role of anti-HBV treatment in improving prognosis remains uncertain and warrants further investigation. Acute HEV infection superimposed on chronic HBV infection poses significant clinical challenges, with outcomes ranging from full recovery to fatality. Preventive measures, including sanitation and vaccination against HBV, are crucial. More studies are needed to establish effective treatment protocols for this co-infection. In this study, we will analyze the clinical setting, diagnosis, particularities, and outcomes of five such cases of dual hepatotropic viral infection recorded over a period of 6 years (2018-2023) at a large Infectious Diseases clinic in Bucharest, Romania.
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Affiliation(s)
- Mihaela-Cristina Olariu
- Department of Infectious Diseases, University of Medicine and Pharmacy “Carol Davila”, 020021 Bucharest, Romania;
- National Institute for Infectious Diseases “Matei Balș”, 021105 Bucharest, Romania; (M.-C.F.); (A.M.B.)
| | - Mihai-Cezar Filipescu
- National Institute for Infectious Diseases “Matei Balș”, 021105 Bucharest, Romania; (M.-C.F.); (A.M.B.)
| | - Andreea Marilena Pauna
- Department of Epidemiology I, University of Medicine and Pharmacy “Carol Davila”, 020021 Bucharest, Romania
- Military Medical Institute, 010919 Bucharest, Romania
| | - Madalina Simoiu
- National Institute for Infectious Diseases “Matei Balș”, 021105 Bucharest, Romania; (M.-C.F.); (A.M.B.)
- Department of Parasitology, University of Medicine and Pharmacy “Carol Davila”, 020021 Bucharest, Romania
| | - Alina Maria Borcan
- National Institute for Infectious Diseases “Matei Balș”, 021105 Bucharest, Romania; (M.-C.F.); (A.M.B.)
- Department of Microbiology, University of Medicine and Pharmacy “Carol Davila”, 020021 Bucharest, Romania
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Alexandrova R, Tsachev I, Kirov P, Abudalleh A, Hristov H, Zhivkova T, Dyakova L, Baymakova M. Hepatitis E Virus (HEV) Infection Among Immunocompromised Individuals: A Brief Narrative Review. Infect Drug Resist 2024; 17:1021-1040. [PMID: 38505248 PMCID: PMC10948336 DOI: 10.2147/idr.s449221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 02/21/2024] [Indexed: 03/21/2024] Open
Abstract
Hepatitis E virus (HEV) is a single-stranded positive-sense RNA virus that belongs to Hepeviridae family. HEV is the most common cause of acute viral hepatitis worldwide. According to the World Health Organization (WHO), there are estimated 20 million HEV infections worldwide every year, leading to estimated 3.3 million symptomatic cases of HEV infection. The WHO estimates that HEV infection caused approximately 44,000 deaths in 2015, which represents 3.3% of mortality rates due to viral hepatitis. In low-income (LI) countries and lower-middle-income (LMI) countries, HEV is a waterborne infection induced by HEV genotype (gt) 1 and HEV gt 2 that cause large outbreaks and affect young individuals with a high mortality rate in pregnant women from South Asian countries and patients with liver diseases. HEV gt 3, HEV gt 4, and HEV gt 7 are responsible for sporadic infections with zoonotic transmission mainly through the consumption of raw or undercooked meat from different animals. Acute HEV infection is relatively asymptomatic or mild clinical form, in rare cases the disease can be moderate/severe clinical forms and result in fulminant hepatitis or acute liver failure (ALF). Furthermore, HEV infection is associated with extrahepatic manifestations, including renal and neurological clinical signs and symptoms. Pregnant women, infants, older people, immunocompromised individuals, patients with comorbidities, and workers who come into close contact with HEV-infected animals are recognized as major risk groups for severe clinical form of HEV infection and fatal outcome. Chronic HEV infection can occur in immunocompromised individuals with the possibility of progression to cirrhosis.
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Affiliation(s)
- Radostina Alexandrova
- Department of Pathology, Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Ilia Tsachev
- Department of Microbiology, Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, Trakia University, Stara Zagora, Bulgaria
| | - Plamen Kirov
- Department of Pathology, Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Abedulkadir Abudalleh
- Department of Pathology, Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Hristo Hristov
- Department of Pathology, Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Tanya Zhivkova
- Department of Pathology, Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Lora Dyakova
- Department of Synaptic Signaling and Communication, Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Magdalena Baymakova
- Department of Infectious Diseases, Military Medical Academy, Sofia, Bulgaria
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Wang N, He S, Zheng Y, Wang L. Efficacy and safety of tenofovir disoproxil fumarate versus entecavir in the treatment of acute-on-chronic liver failure with hepatitis B: a systematic review and meta-analysis. BMC Gastroenterol 2023; 23:388. [PMID: 37957546 PMCID: PMC10642028 DOI: 10.1186/s12876-023-03024-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 10/31/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Oral nucleoside (acid) analogues (NAs) are recommended for patients with acute-on-chronic liver failure (ACLF) associated with hepatitis B virus (HBV-ACLF). The efficacy and safety of tenofovir (TDF) and entecavir (ETV) in these patients remain unclear. METHODS A comprehensive literature search in PubMed, Web of Science, The Cochrane Library, and Embase database was conducted to select studies published before December 2022 on TDF or ETV for HBV-ACLF. The primary outcomes were survival rates at 4, 12, and 48 weeks. Secondary outcomes were virologic and biochemical responses, serum antigen conversion, liver function score, and safety. RESULTS Four prospective and one retrospective cohort studies were selected. The overall analysis showed comparable survival rates at 4, 12, and 48 weeks for all patients receiving TDF or ETV (4-week: RR = 1.17, 95% CI: 0.90-1.51, p = 0.24; 12-week: RR = 1.00, 95% CI: 0.88-1.13, p = 0.94; 48-week: RR = 0.96, 95% CI: 0.58-1.57, p = 0.86). Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score at 12 weeks were comparable in both groups but lower than baseline (CTP: SMD = -0.75, 95% CI:-2.81-1.30, p = 0.47; MELD: SMD = -1.10, 95% CI:-2.29-0.08, p = 0.07). At 48 weeks, estimated glomerular filtration rate (eGFR) levels were found to decrease to different degrees from baseline in both the TDF and ETV groups, and the decrease was greater in the TDF group than in the ETV group. No significant differences were found in biochemical, virologic response, and serum antigen conversion between the two groups during the observation period. CONCLUSION TDF treatment of HBV-ACLF is similar to ETV in improving survival, liver function, and virologic response but the effects on renal function in two groups in the long term remain unclear. More and larger long-term clinical trials are required to confirm these findings.
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Affiliation(s)
- Neng Wang
- Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China
| | - Sike He
- West China School of Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Yu Zheng
- Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China
| | - Lichun Wang
- Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
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Tafesh ZH, Salcedo RO, Pyrsopoulos NT. Classification and Epidemiologic Aspects of Acute-on-Chronic Liver Failure. Clin Liver Dis 2023; 27:553-562. [PMID: 37380282 DOI: 10.1016/j.cld.2023.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/30/2023]
Abstract
The three most common definitions of acute-on-chronic liver failure (ACLF) are derived from data from North America, Europe, and the Asian-Pacific Region. All three definitions identify patients with underlying liver disease who are at increased risk for mortality who develop a syndrome often characterized by associated organ failures. The epidemiology of ACLF differs throughout various regions globally and is driven by the cause of the underlying chronic liver disease and the triggers of ACLF.
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Affiliation(s)
- Zaid H Tafesh
- Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, 185 South Orange Avenue, MSB H Room-534, Newark, NJ 07103, USA
| | - Raquel Olivo Salcedo
- Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, 185 South Orange Avenue, MSB H Room-532, Newark, NJ 07103, USA
| | - Nikolaos T Pyrsopoulos
- Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, 185 South Orange Avenue, MSB H Room-536, Newark, NJ 07103, USA.
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9
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Bhatti TK, Singal AK, Kwo PY. Viral Hepatitis and Acute-on-Chronic Liver Failure. Clin Liver Dis 2023; 27:617-630. [PMID: 37380286 DOI: 10.1016/j.cld.2023.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/30/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is a potentially reversible syndrome that develops in patients with cirrhosis or with underlying chronic liver disease (CLD) and is characterized by acute decompensation, organ failure, and high short-term mortality. Hepatitis A and hepatitis E are major causes of ACLF. Hepatitis B may also cause ACLF through a flare of hepatitis B, acute infection, or reactivation. Besides supportive care, nucleoside/nucleotide analog therapy should also be initiated in this setting. Nonhepatotropic viruses may rarely also cause ACLF with the severe acute respiratory syndrome coronavirus 2 virus recently being identified with poorer outcomes in those with underlying CLD.
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Affiliation(s)
| | - Ashwani K Singal
- University of SD Sanford School of Medicine, Sioux Falls, SD, USA
| | - Paul Y Kwo
- Stanford University School of Medicine, Palo Alto, CA, USA.
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10
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Marginean CM, Pirscoveanu D, Popescu M, Vasile CM, Docea AO, Mitruț R, Mărginean IC, Iacob GA, Firu DM, Mitruț P. Challenges in Diagnosis and Therapeutic Approach of Acute on Chronic Liver Failure-A Review of Current Evidence. Biomedicines 2023; 11:1840. [PMID: 37509478 PMCID: PMC10376368 DOI: 10.3390/biomedicines11071840] [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: 05/29/2023] [Revised: 06/23/2023] [Accepted: 06/25/2023] [Indexed: 07/30/2023] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute and severe decompensation of chronic liver disease (CLD) correlated with multiple organ failure, poor prognosis, and increased mortality. In 40-50% of ACLF cases, the trigger is not recognized; for many of these patients, bacterial translocation associated with systemic inflammation is thought to be the determining factor; in the other 50% of patients, sepsis, alcohol consumption, and reactivation of chronic viral hepatitis are the most frequently described trigger factors. Other conditions considered precipitating factors are less common, including acute alcoholic hepatitis, major surgery, TIPS insertion, or inadequate paracentesis without albumin substitution. Host response is likely the primary factor predicting ACLF severity and prognosis, the host immune response having a particular significance in this syndrome, together with the inflammatory cascade. The management of ACLF includes both the prevention of the precipitating factors that lead to acute liver decompensation and the support of vital functions, the prevention and management of complications, the estimation of prognosis, and the opportunity for liver transplantation.
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Affiliation(s)
- Cristina Maria Marginean
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Denisa Pirscoveanu
- Department of Neurology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Mihaela Popescu
- Department of Endocrinology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Corina Maria Vasile
- Department of Pediatric Cardiology, "Marie Curie" Emergency Children's Hospital, 041451 Bucharest, Romania
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Radu Mitruț
- Department of Cardiology, University and Emergency Hospital, 050098 Bucharest, Romania
| | | | - George Alexandru Iacob
- Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dan Mihai Firu
- Ph.D. School Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Paul Mitruț
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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11
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Jindal A, Sarin SK. Epidemiology of liver failure in Asia-Pacific region. Liver Int 2022; 42:2093-2109. [PMID: 35635298 DOI: 10.1111/liv.15328] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 05/26/2022] [Accepted: 05/27/2022] [Indexed: 02/13/2023]
Abstract
The global burden of deaths caused by liver failure is substantial. The Asia-Pacific region is home to more than half of the global population and accounted for 62.6% of global deaths because of liver diseases in 2015. The aetiology of liver failure varies in different countries at different times. Viruses (Hepatitis A, B and E), drugs (herbs and anti-tuberculous drugs), toxins (alcohol use) and autoimmune flares are mainly responsible of majority of liver failure in individuals with normal liver (acute liver failure; ALF); else these may precipitate liver failure in those with chronic liver disease (acute-on-chronic liver failure; ACLF). Concomitant increases in alcohol misuse and metabolic syndrome in recent years are concerning. Ongoing efforts to address liver failure-related morbidity and mortality require accurate contemporary estimates of epidemiology and outcomes. In light of the ever-changing nature of liver disease epidemiology, accurate estimates for the burden of liver failure across the countries are vital for setting clinical, research and policy priorities. In this review, we aimed to describe the current as well as changing epidemiological trends of common liver failure syndromes, ALF and ACLF in the Asia-Pacific region.
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Affiliation(s)
- Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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12
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Wu S, Yi W, Gao Y, Deng W, Bi X, Lin Y, Yang L, Lu Y, Liu R, Chang M, Shen G, Hu L, Zhang L, Li M, Xie Y. Immune Mechanisms Underlying Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B Patients With Viral Coinfection. Front Immunol 2022; 13:893512. [PMID: 35634301 PMCID: PMC9130599 DOI: 10.3389/fimmu.2022.893512] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 04/11/2022] [Indexed: 12/28/2022] Open
Abstract
It is considered that chronic hepatitis B patients have obtained functional cure if they get hepatitis B surface antigen (HBsAg) seroclearance after treatment. Serum HBsAg is produced by cccDNA that is extremely difficult to clear and dslDNA that is integrated with host chromosome. High HBsAg serum level leads to failure of host immune system, which makes it unable to produce effective antiviral response required for HBsAg seroclerance. Therefore, it is very difficult to achieve functional cure, and fewer than 1% of chronic hepatitis B patients are cured with antiviral treatment annually. Some chronic hepatitis B patients are coinfected with other chronic viral infections, such as HIV, HCV and HDV, which makes more difficult to cure. However, it is found that the probability of obtaining HBsAg seroclearance in patients with coinfection is higher than that in patients with HBV monoinfection, especially in patients with HBV/HIV coinfection who have an up to 36% of HBsAg 5-year-seroclerance rate. The mechanism of this interesting phenomenon is related to the functional reconstruction of immune system after antiretroviral therapy (ART). The quantity increase and function recovery of HBV specific T cells and B cells, and the higher level of cytokines and chemokines such as IP-10, GM-CSF, promote HBsAg seroclearance. This review summarizes recent studies on the immune factors that have influence on HBsAg seroconversion in the chronic hepatitis B patients with viral coinfection, which might provide new insights for the development of therapeutic approaches to partially restore the specific immune response to HBV and other viruses.
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Affiliation(s)
- Shuling Wu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wei Yi
- Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuanjiao Gao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wen Deng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoyue Bi
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yanjie Lin
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Liu Yang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ruyu Liu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Min Chang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ge Shen
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Leiping Hu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
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13
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Choi JW, Son HJ, Lee SS, Jeon H, Cho JK, Kim HJ, Cha RR, Lee JM, Kim HJ, Jung WT, Lee OJ. Acute hepatitis E virus superinfection increases mortality in patients with cirrhosis. BMC Infect Dis 2022; 22:62. [PMID: 35042464 PMCID: PMC8767750 DOI: 10.1186/s12879-022-07050-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 01/12/2022] [Indexed: 12/20/2022] Open
Abstract
Background Although acute hepatitis E is not fatal in healthy individuals, it is unclear whether hepatitis E superinfection increases the mortality in patients with pre-existing liver disease. Thus, we investigated the prognosis of patients with acute hepatitis E according to their cirrhosis diagnosis, and the prognosis according to the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis and chronic liver disease (CLD).
Methods This study included 74 consecutive patients who were diagnosed with acute viral hepatitis E between January 2007 and December 2019. Of them, 39 patients without CLD, 13 patients with non-cirrhotic CLD, and 22 patients with cirrhotic CLD were analyzed.
Results Among the 74 patients with HEV infection, 7 (9.5%) died within 180 days: 5 with underlying cirrhosis (71.4%) and 2 without cirrhosis (28.6%). The 180-day mortality was significant higher for patients with cirrhosis than for patients without cirrhosis (22.7% vs. 3.8%, P = 0.013). The age- and sex-adjusted proportional-hazard model revealed an approximately eightfold increase in the 180-day mortality risk in patients with cirrhosis compared to patients without cirrhosis. In addition, development of hepatitis E virus-related ACLF due to acute liver function deterioration in patients with pre-existing CLD or cirrhosis worsened the 180-day mortality rate. Conclusions Our findings suggest that the acute hepatitis E mortality rate was low in healthy individuals but higher in patients with cirrhosis, and especially high in those with ACLF. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-022-07050-w.
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14
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Fantilli A, López Villa SD, Zerega A, Di Cola G, López L, Wassaf Martínez M, Pisano MB, Ré VE. Hepatitis E virus infection in a patient with alcohol related chronic liver disease: a case report of acute-on-chronic liver failure. Virol J 2021; 18:245. [PMID: 34886883 PMCID: PMC8662871 DOI: 10.1186/s12985-021-01714-w] [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: 07/30/2021] [Accepted: 11/26/2021] [Indexed: 02/07/2023] Open
Abstract
Background The hepatitis E virus (HEV) infection has been described as a causing factor for acute-on-chronic-liver-failure (ACLF) in patients with underlying chronic liver disease (CLD), such as chronic hepatitis or cirrhosis, which could end in the failure of one or more organs and high short-term mortality. There are scarce data about the association of HEV in patients with chronic liver disorders in South America. Case presentation A 56-year-old hypertensive male with a history of type 2 diabetes was diagnosed with alcohol-related-liver cirrhosis in February 2019. A year later, the patient was admitted to hospital due to fatigue, jaundice and acholia. No evidence of hepatitis A virus, hepatitis B virus, hepatitis C virus, Epstein–Barr virus, herpes zoster virus and cytomegalovirus infections were found. Nevertheless, in February and March, 2020 the patient was positive for HEV-IgM and HEV-IgG, and HEV genotype 3 RNA was detected in sera. Afterwards, he presented grade I hepatic encephalopathy and, therefore, was diagnosed with acute hepatitis E-on-chronic liver disease. The patient reported a recent travel to the Argentine coast, where he consumed seafood. Besides, he reveled to have consumed pork meat and had no history of blood transfusion. Conclusion This report describes a unique case of hepatitis E virus infection in a patient with alcohol-related cirrhosis. This is the first report of a patient with HEV-related ACLF in Argentina and it invokes the importance of HEV surveillance and treatment among patients with CLD, such as alcohol-related cirrhosis.
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Affiliation(s)
- Anabella Fantilli
- Instituto de Virología "Dr. J. M. Vanella"- InViV- CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016, Córdoba, Argentina.
| | | | | | - Guadalupe Di Cola
- Instituto de Virología "Dr. J. M. Vanella"- InViV- CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016, Córdoba, Argentina
| | - Luis López
- Instituto Modelo de Cardiología, Córdoba, Argentina
| | | | - María Belén Pisano
- Instituto de Virología "Dr. J. M. Vanella"- InViV- CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016, Córdoba, Argentina
| | - Viviana Elizabeth Ré
- Instituto de Virología "Dr. J. M. Vanella"- InViV- CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016, Córdoba, Argentina
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15
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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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16
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Khanam A, Kottilil S. Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management. Front Med (Lausanne) 2021; 8:752875. [PMID: 34820395 PMCID: PMC8606418 DOI: 10.3389/fmed.2021.752875] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 10/07/2021] [Indexed: 12/21/2022] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a multifaceted condition with poor treatment options and high short-term mortality. ACLF can develop in patients with or without liver cirrhosis, where patients with decompensated cirrhosis display a higher risk of short-term mortality. Pathophysiological mechanisms include systemic inflammation due to bacterial and fungal infections and acute hepatic insult with drug, alcohol, and viral hepatitis. Cryptogenic factors also contribute to the development of ACLF. The clinical outcome of patients with ACLF gets further complicated by the occurrence of variceal hemorrhage, hepatorenal syndrome, hepatic encephalopathy, and systemic immune dysfunction. Regardless of the better understanding of pathophysiological mechanisms, no specific and definitive treatment is available except for liver transplantation. The recent approach of regenerative medicine using mesenchymal stem cells (MSCs) could be advantageous for the treatment of ACLF as these cells can downregulate inflammatory response by inducing antiinflammatory events and prevent hepatic damage and fibrosis by inhibiting hepatic stellate cell activation and collagen synthesis. Moreover, MSCs are involved in tissue repair by the process of liver regeneration. Considering the broad therapeutic potential of MSCs, it can serve as an alternative treatment to liver transplant in the near future, if promising results are achieved.
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Affiliation(s)
- Arshi Khanam
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Shyam Kottilil
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, United States
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17
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Fan H, Fan J, Chen S, Chen Y, Gao H, Shan L, Li X, Gu F, Zhuang H, Sun L. Prognostic Significance of End-Stage Liver Diseases, Respiratory Tract Infection, and Chronic Kidney Diseases in Symptomatic Acute Hepatitis E. Front Cell Infect Microbiol 2021; 10:593674. [PMID: 33520734 PMCID: PMC7843426 DOI: 10.3389/fcimb.2020.593674] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Accepted: 11/25/2020] [Indexed: 01/06/2023] Open
Abstract
Symptomatic hepatitis E virus (HEV) infection is sporadic, and usually occurs in a limited number of infected patients, which hinders the investigation of risk factors for clinical outcomes in patients with acute HEV infection. A retrospective cohort study enrolling 1913 patients with symptomatic acute hepatitis E in Beijing 302 Hospital from January 1, 2001 to December 31, 2018 was conducted. The baseline characteristics, clinical features and laboratory data of these HEV infection cases were analyzed. Albumin (ALB), platelet (PLT), alanine aminotransferase (ALT), total bilirubin (T-BiL), international normalized ratio (INR) and serum creatinine (SCR) levels, along with the model for end-stage liver disease (MELD) score, hospitalization days, co-morbidity number and mortality were taken as major parameters for comparing the clinical manifestations in our study. We found that not all pre-existing chronic liver diseases exacerbate clinical manifestations of acute hepatitis E. Alcoholic hepatitis, fatty liver hepatitis, hepatic cyst, drug-induced hepatitis and hepatocellular carcinoma were not significantly associated with mortality of HEV patients. Among all of the comorbidities, end-stage liver diseases (ESLDs, including ascites, cirrhosis, hepatic coma and hepatorenal syndrome), respiratory tract infection and chronic kidney diseases (CKDs, including renal insufficiency and renal failure) were found to remarkably increase the mortality of patients with symptomatic HEV infection. Furthermore, the severity evaluation indexes (SEI), such as MELD score, duration of hospital stay, and co-morbidity number in HEV patients with underlying comorbidities were much worse than that of their counterparts without relevant comorbidities.
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Affiliation(s)
- Huahao Fan
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Junfen Fan
- Institute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China
| | - Suming Chen
- The Medical Center of Clinical Laboratory, Beijing 302 Hospital/The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Yangzhen Chen
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Huiru Gao
- The Medical Center of Clinical Laboratory, Beijing 302 Hospital/The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Liying Shan
- The Medical Center of Clinical Laboratory, Beijing 302 Hospital/The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Xue Li
- The Medical Center of Clinical Laboratory, Beijing 302 Hospital/The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Fengjun Gu
- Medical Information Center, Beijing 302 Hospital/The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Hui Zhuang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Lijun Sun
- Research Center for Clinical and Translational Medicine, Beijing 302 Hospital/The Fifth Medical Center of PLA General Hospital, Beijing, China
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18
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Sun L, Fan J, Gao H, Shan L, Li X, Zhuang H, Fan H. Clinical Outcomes in Patients with Acute Hepatitis E: Exacerbation by Background End-Stage Liver Disease but Not Pure Hepatitis B Virus Infection. Clin Infect Dis 2021; 70:2747-2748. [PMID: 31367754 DOI: 10.1093/cid/ciz724] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Affiliation(s)
- Lijun Sun
- Research Center for Clinical and Translational Medicine, Beijing 302 Hospital/The Fifth Medical Center of PLA General Hospital, Beijing, China; China
| | - Junfen Fan
- Institute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China; China
| | - Huiru Gao
- The Medical Center of Clinical Laboratory, Beijing 302 Hospital/The Fifth Medical Center of PLA General Hospital, Beijing, China; China
| | - Liying Shan
- The Medical Center of Clinical Laboratory, Beijing 302 Hospital/The Fifth Medical Center of PLA General Hospital, Beijing, China; China
| | - Xue Li
- The Medical Center of Clinical Laboratory, Beijing 302 Hospital/The Fifth Medical Center of PLA General Hospital, Beijing, China; China
| | - Hui Zhuang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; China
| | - Huahao Fan
- Institute of Infectious Disease, Pediatric Liver Disease Therapy and Research Center, Beijing 302 Hospital/The Fifth Medical Center of PLA General Hospital, Beijing, China
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19
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Thakur V, Ratho RK, Kumar S, Saxena SK, Bora I, Thakur P. Viral Hepatitis E and Chronicity: A Growing Public Health Concern. Front Microbiol 2020; 11:577339. [PMID: 33133046 PMCID: PMC7550462 DOI: 10.3389/fmicb.2020.577339] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 09/03/2020] [Indexed: 12/15/2022] Open
Abstract
Hepatitis E viral infection recently emerges as a global health concern. Over the last decade, the understanding of hepatitis E virus (HEV) had changed with the discovery of new genotypes like genotype-7 and genotype-8 with associated host and mode of infection. Diversification in the mode of hepatitis E infection transmission through blood transfusion, and organ transplants in contrast to classical feco-oral and zoonotic mode is the recent medical concern. The wide spectrum of infection ranging from self-limiting to acute liver failure is now overpowered by HEV genotype-specific chronic infection especially in transplant patients. This concern is further escalated by the extra-hepatic manifestations of HEV targeting the central nervous system (CNS), kidney, heart, and pancreas. However, with the development of advanced efficient cell culture systems and animal models simulating the infection, much clarity toward understanding the pathogenetic mechanism of HEV has been developed. Also this facilitates the development of vaccines research or therapeutics. In this review, we highlight all the novel findings in every aspect of HEV with special emphasis on recently emerging chronic mode of infection with specific diagnosis and treatment regime with an optimistic hope to help virologists and/or liver specialists working in the field of viral hepatitis.
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Affiliation(s)
- Vikram Thakur
- Department of Virology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Radha Kanta Ratho
- Department of Virology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Swatantra Kumar
- Centre for Advanced Research, Faculty of Medicine, King George's Medical University, Lucknow, India
| | - Shailendra K Saxena
- Centre for Advanced Research, Faculty of Medicine, King George's Medical University, Lucknow, India
| | - Ishani Bora
- Department of Virology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Pryanka Thakur
- Department of Virology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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20
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Nasir M, Wu GY. HEV and HBV Dual Infection: A Review. J Clin Transl Hepatol 2020; 8:313-321. [PMID: 33083255 PMCID: PMC7562801 DOI: 10.14218/jcth.2020.00030] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 05/29/2020] [Accepted: 06/07/2020] [Indexed: 12/17/2022] Open
Abstract
Hepatitis E virus (HEV) is a global health problem, affecting about 20 million people worldwide. There is significant overlap of hepatitis B virus (HBV) and HEV endemicity in many Asian countries where dual infections with HEV and HBV can occur. Though the clinical course of HEV is largely self-limited, HEV superinfection in patients with chronic hepatitis B (CHB) can result in acute exacerbation of underlying CHB. HEV superinfection in patients with CHB-related cirrhosis has been identified as a risk factor for decompensated cirrhosis and an independent predictor of mortality. Whereas acute HEV infection in pregnancy can cause fulminant liver failure, the few studies on pregnant patients with dual HBV and HEV infection have shown a subclinical course. Immunosuppression is a risk factor for the development of chronic HEV infection, which can be managed by decreasing the dose of immune-suppressants and administering ribavirin. Vaccination for HEV has been developed and is in use in China but its efficacy in patients with CHB has yet to be established in the USA. In this review, we appraise studies on dual infection with HEV and HBV, including the effect of HEV superinfection and coinfection in CHB, management strategies used and the role of active vaccination in the prevention of HEV.
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Affiliation(s)
- Myra Nasir
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
- Correspondence to: Myra Nasir, Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA. Tel: +1-860-470-6616, E-mail:
| | - George Y. Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
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21
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Co-Occurrence of Hepatitis A Infection and Chronic Liver Disease. Int J Mol Sci 2020; 21:ijms21176384. [PMID: 32887515 PMCID: PMC7504211 DOI: 10.3390/ijms21176384] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 08/23/2020] [Accepted: 09/01/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatitis A virus (HAV) infection occasionally leads to a critical condition in patients with or without chronic liver diseases. Acute-on-chronic liver disease includes acute-on-chronic liver failure (ACLF) and non-ACLF. In this review, we searched the literature concerning the association between HAV infection and chronic liver diseases in PubMed. Chronic liver diseases, such as metabolic associated fatty liver disease and alcoholic liver disease, coinfection with other viruses, and host genetic factors may be associated with severe hepatitis A. It is important to understand these conditions and mechanisms. There may be no etiological correlation between liver failure and HAV infection, but there is an association between the level of chronic liver damage and the severity of acute-on-chronic liver disease. While the application of an HAV vaccination is important for preventing HAV infection, the development of antivirals against HAV may be important for preventing the development of ACLF with HAV infection as an acute insult. The latter is all the more urgent given that the lives of patients with HAV infection and a chronic liver disease of another etiology may be at immediate risk.
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22
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Lai JCT, Wong VWS, Wong GLH. Reply to Sun et al. Clin Infect Dis 2020; 70:2748-2749. [DOI: 10.1093/cid/ciz725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Jimmy Che-To Lai
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, China
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, China
- Institute of Digestive Disease, Chinese University of Hong Kong, China
- State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, China
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, China
- Institute of Digestive Disease, Chinese University of Hong Kong, China
- State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, China
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23
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Noninvasive models for predicting poor prognosis of chronic HBV infection patients precipitating acute HEV infection. Sci Rep 2020; 10:2753. [PMID: 32066795 PMCID: PMC7026406 DOI: 10.1038/s41598-020-59670-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Accepted: 02/03/2020] [Indexed: 12/23/2022] Open
Abstract
Hepatitis E virus (HEV) infection contributes to a considerable proportion of acute-on-chronic liver failure (ACLF) in patients with chronic hepatitis B virus (HBV) infection. This study aimed to predict the prognosis of chronic HBV infection patients precipitating acute HEV infection. A total of 193 patients were enrolled in this study. The performances of three chronic liver disease prognostic models (CTP score, MELD score, and CLIF-C ADs) were analyzed for predicting the development of ACLF following HEV superimposing chronic HBV infection. Subsequently, the performances of five ACLF prognostic assessment models (CTP score, MELD score, CLIF-C ACLFs, CLIF-C OFs, and COSSH-ACLFs) were analyzed for predicting the outcome of those ACLF patients. Of 193 chronic HBV infection patients precipitating acute HEV infection, 13 patients were diagnosed ACLF on admission, 54 patients developed to ACLF after admission, and 126 patients had non-ACLF during the stay in hospital. For predicting the development of ACLF, CTP score yielded a significantly higher AUROC compared with MELD score and CLIF-C ADs (0.92, 0.88, and 0.86, respectively; all p < 0.05). For predicting the poor prognosis of ACLF patients, the COSSH-ACLFs yielded a significantly higher AUROC compared with CLIF-C ACLFs, CLIF-C OFs, MELD score, and CTP score (0.89, 0.83, 0.81, 0.67, and 0.58, respectively; all p < 0.05). In conclusion, the stepwise application of CTP score and COSSH-ACLFs can predict the prognosis of chronic HBV infection patients precipitating acute HEV infection.
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24
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Arora V, Jagdish RK, Sarin SK. Acute-on-Chronic Liver Failure. LIVER IMMUNOLOGY 2020:525-537. [DOI: 10.1007/978-3-030-51709-0_32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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25
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Wang Y, Liu H, Liu S, Yang C, Jiang Y, Wang S, Liu A, Peppelenbosch MP, Kamar N, Pan Q, Zhao J. Incidence, predictors and prognosis of genotype 4 hepatitis E related liver failure: A tertiary nested case-control study. Liver Int 2019; 39:2291-2300. [PMID: 31436371 DOI: 10.1111/liv.14221] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 07/25/2019] [Accepted: 08/12/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND/AIMS Hepatitis E virus (HEV) infection has been recognized an important insult of acute or acute-on-chronic liver failure (A(C)LF). This study aimed to identify the incidence, predictors and outcomes of A(C)LF in patients with hepatitis E. METHODS All patients diagnosed of hepatitis E between 2012 and 2018 in the tertiary hospital were retrospectively and consecutively analysed. Patients with hepatitis E who developed A(C)LF were enrolled as cases (HEV-LF) and controls were randomly selected from those who did not develop liver failure with 1:3 ratio in the same cohort. RESULTS Eight hundred and nine patients were diagnosed with hepatitis E, among which 80 were identified with HEV-related liver failure (HEV-LF) with HEV as the solely acute aetiology of A(C)LF. Sequencing of HEV genome showed genotype (GT) 4 strains in all available serum samples. Hepatitis E patients with cirrhosis underwent higher risk to develop liver failure, compared to non-cirrhotic patients. Hydrothorax, respiratory infections, lower γ-glutamyl transferase, higher lactate dehydrogenase and alpha-foetoprotein were found to be independent predictors of A(C)LF in patients with hepatitis E. The 28-day and 90-day mortality for HEV-LF was 12.86% and 30.36% respectively. Renal injury and lower triglyceride were independent factors associated with 28-day mortality. Lower alanine aminotransferase and higher International normalized ratio were independent predictors of 90-day mortality. CONCLUSIONS Patients with GT4 hepatitis E are at high risk to develop A(C)LF. Different CLD status impacted the incidence of HEV-LF distinctively. The identified variables shall help to identify HEV patients with high risk for developing liver failure and the risk for death.
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Affiliation(s)
- Yijin Wang
- Department of Pathology and Hepatology, the 5thMedical Centre, Chinese people's Liberation Army General Hospital, Beijing, China
| | - Hongyang Liu
- Department of Pathology and Hepatology, the 5thMedical Centre, Chinese people's Liberation Army General Hospital, Beijing, China.,Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands
| | - Shuhong Liu
- Department of Pathology and Hepatology, the 5thMedical Centre, Chinese people's Liberation Army General Hospital, Beijing, China
| | - Changshuang Yang
- Department of Pathology and Hepatology, the 5thMedical Centre, Chinese people's Liberation Army General Hospital, Beijing, China
| | - Yiyun Jiang
- Department of Pathology and Hepatology, the 5thMedical Centre, Chinese people's Liberation Army General Hospital, Beijing, China.,Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands
| | - Shan Wang
- Department of Pathology and Hepatology, the 5thMedical Centre, Chinese people's Liberation Army General Hospital, Beijing, China
| | - Aixia Liu
- Department of Laboratory Medicine, the 5th Medical Centre, Chinese people's Liberation Army General Hospital, Beijing, China
| | - Maikel P Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands
| | - Nassim Kamar
- Chef du Pôle Urologie-Néphrologie-UTO-Dialyse, Coordonateur du Département de Néphrologie et Transplantation d'Organes, CHU Rangueil, Toulouse, France
| | - Qiuwei Pan
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands
| | - Jingmin Zhao
- Department of Pathology and Hepatology, the 5thMedical Centre, Chinese people's Liberation Army General Hospital, Beijing, China
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26
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Kilonzo SB, Gunda D, Ning Q, Han M. Where Hepatitis B and Hepatitis E Meet: Epidemiological and Clinical Aspects. HEPATITIS MONTHLY 2019; 19. [DOI: 10.5812/hepatmon.93840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Accepted: 07/09/2019] [Indexed: 08/30/2023]
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27
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Superinfective Hepatitis E Virus Infection Aggravates Hepatocytes Injury in Chronic Hepatitis B. Curr Med Sci 2019; 39:719-726. [PMID: 31612388 DOI: 10.1007/s11596-019-2097-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 05/05/2019] [Indexed: 12/16/2022]
Abstract
Hepatitis E virus (HEV) infection is a major cause of morbidity in endemic areas. Its consequences among chronic hepatitis B (CHB) patients have been under-reported. The aim of this study was to assess the impact of superinfective HEV infection (acute and past) on virological and clinical features of patients with CHB infection. Clinical, biochemical, virological and immunological data of 153 CHB patients including 98 with hepatitis B virus (HBV) monoinfection and 55 with HBV-HEV superinfection with both HEV and HBV infection was retrospectively investigated and analyzed in this study conducted in Wuhan, China. An overall anti-HEV IgG seroprevalence was found to be 35.9% in CHB patients. HBV-HEV superinfection patients showed significantly higher rate of complications (ascites, hepato-renal syndrome & encephalopathy) (all with P=0.04), cirrhosis (P<0.001) and acute-on-chronic liver failure (P<0.001) than HBV monoinfection patients. They also displayed elevated ALTs (P<0.001) and total serum bilirubin (P<0.001) with diminished albumin (P<0.001) and HBV viral load (P<0.001). Cytokines assay revealed increased expression of IL-6 (P=0.02), IL-10 (P=0.009) and TNF-α (P=0.003) in HBV-HEV superinfection patients compared to HBV monoinfection patients. Our study demonstrated that HEV superinfection in CHB patients was associated with progressive clinical manifestation, which is likely due to the enhanced expression of cytokines related with hepatocytes necrosis. HEV was also associated with repressed HBV replication, but the underlying mechanism requires further investigation.
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28
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Win NN, Kanda T, Ogawa M, Nakamoto S, Haga Y, Sasaki R, Nakamura M, Wu S, Matsumoto N, Matsuoka S, Kato N, Shirasawa H, Yokosuka O, Okamoto H, Moriyama M. Superinfection of hepatitis A virus in hepatocytes infected with hepatitis B virus. Int J Med Sci 2019; 16:1366-1370. [PMID: 31692913 PMCID: PMC6818197 DOI: 10.7150/ijms.32795] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 06/07/2019] [Indexed: 12/20/2022] Open
Abstract
Hepatitis A virus (HAV) infection is a major cause of acute hepatitis including acute liver failure. Hepatitis B infection (HBV) occurs worldwide, with the highest rates in Asian and African countries, and there are several reports that HAV infection may have a more severe clinical course in patients with chronic HBV infection. We previously demonstrated that Japanese miso extracts have inhibitory effects on HAV replication. In the present study, we examined the replication of HAV and HBV in a hepatocyte superinfection model and the inhibitory effects of Japanese miso extracts on both viruses. According to the results, HAV infection inhibited HBV replication in superinfected hepatocytes, and Japanese rice-koji miso extracts had inhibitory effects on HAV replication. Our findings provide useful information for clinicians in managing HAV infection in patients with chronic HBV infection.
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Affiliation(s)
- Nan Nwe Win
- Department of Molecular Virology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8677, Japan
| | - Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan; (T.K.)
| | - Masahiro Ogawa
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan; (T.K.)
| | - Shingo Nakamoto
- Department of Molecular Virology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8677, Japan
- Department of Gastroenterology, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8677, Japan
| | - Yuki Haga
- Department of Gastroenterology, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8677, Japan
| | - Reina Sasaki
- Department of Gastroenterology, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8677, Japan
| | - Masato Nakamura
- Department of Gastroenterology, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8677, Japan
| | - Shuang Wu
- Department of Gastroenterology, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8677, Japan
| | - Naoki Matsumoto
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan; (T.K.)
| | - Shunichi Matsuoka
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan; (T.K.)
| | - Naoya Kato
- Department of Gastroenterology, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8677, Japan
| | - Hiroshi Shirasawa
- Department of Molecular Virology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8677, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8677, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan
| | - Mitsuhiko Moriyama
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan; (T.K.)
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Wu T, Li J, Shao L, Xin J, Jiang L, Zhou Q, Shi D, Jiang J, Sun S, Jin L, Ye P, Yang L, Lu Y, Li T, Huang J, Xu X, Chen J, Hao S, Chen Y, Xin S, Gao Z, Duan Z, Han T, Wang Y, Gan J, Feng T, Pan C, Chen Y, Li H, Huang Y, Xie Q, Lin S, Li L, Li J. Development of diagnostic criteria and a prognostic score for hepatitis B virus-related acute-on-chronic liver failure. Gut 2018; 67:2181-2191. [PMID: 28928275 DOI: 10.1136/gutjnl-2017-314641] [Citation(s) in RCA: 285] [Impact Index Per Article: 40.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Revised: 08/22/2017] [Accepted: 08/23/2017] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The definition of acute-on-chronic liver failure (ACLF) based on cirrhosis, irrespective of aetiology, remains controversial. This study aimed to clarify the clinicopathological characteristics of patients with hepatitis B virus-related ACLF (HBV-ACLF) in a prospective study and develop new diagnostic criteria and a prognostic score for such patients. DESIGN The clinical data from 1322 hospitalised patients with acute decompensation of cirrhosis or severe liver injury due to chronic hepatitis B (CHB) at 13 liver centres in China were used to develop new diagnostic and prognostic criteria. RESULTS Of the patients assessed using the Chronic Liver Failure Consortium criteria with the exception of cirrhosis, 391 patients with ACLF were identified: 92 with non-cirrhotic HBV-ACLF, 271 with cirrhotic HBV-ACLF and 28 with ACLF with cirrhosis caused by non-HBV aetiologies (non-HBV-ACLF). The short-term (28/90 days) mortality of the patients with HBV-ACLF were significantly higher than those of the patients with non-HBV-ACLF. Total bilirubin (TB) ≥12 mg/dL and an international normalised ratio (INR) ≥1.5 was proposed as an additional diagnostic indicator of HBV-ACLF, and 19.3% of patients with an HBV aetiology were additionally diagnosed with ACLF. The new prognostic score (0.741×INR+0.523×HBV-SOFA+0.026×age+0.003×TB) for short-term mortality was superior to five other scores based on both discovery and external validation studies. CONCLUSIONS Regardless of the presence of cirrhosis, patients with CHB, TB ≥12 mg/dL and INR ≥1.5 should be diagnosed with ACLF. The new criteria diagnosed nearly 20% more patients with an HBV aetiology with ACLF, thus increasing their opportunity to receive timely intensive management.
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Affiliation(s)
- Tianzhou Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiang Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Li Shao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiaojiao Xin
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Longyan Jiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qian Zhou
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Dongyan Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jing Jiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Suwan Sun
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Linfeng Jin
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ping Ye
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lingling Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yinyun Lu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jianrong Huang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaowei Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiajia Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shaorui Hao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yuemei Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shaojie Xin
- Department of Liver and Infectious Diseases, No. 302 Hospital of Chinese People's Liberation Army, Beijing, China
| | - Zhiliang Gao
- Department of Liver and Infectious Diseases, The Third Affiliated Hospital, Sun YAT-SEN University, Guangzhou, China
| | - Zhongping Duan
- Department of Liver and Infectious Diseases, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Tao Han
- Department of Liver and Infectious Diseases, Tianjin Third Central Hospital, Tianjin, China
| | - Yuming Wang
- Department of Liver and Infectious Diseases, The First Hospital Affiliated of The Third Military Medical University, Chongqing, China
| | - Jianhe Gan
- Department of Liver and Infectious Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Tingting Feng
- Department of Liver and Infectious Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Chen Pan
- Department of Liver and Infectious Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Yongping Chen
- Department of Liver and Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Hai Li
- Department of Gastroenterology, Renji Hospital Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yan Huang
- Department of Liver and Infectious Diseases, Xiangya Hospital Central South University, Changsha, China
| | - Qing Xie
- Department of Liver and Infectious Diseases, Ruijin Hospital Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Shumei Lin
- Department of Liver and Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jun Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Lai JCT, Wong GLH, Yip TCF, Tse YK, Lam KLY, Lui GCY, Chan HLY, Wong VWS. Chronic Hepatitis B Increases Liver-Related Mortality of Patients With Acute Hepatitis E: A Territorywide Cohort Study From 2000 to 2016. Clin Infect Dis 2018; 67:1278-1284. [PMID: 30265321 DOI: 10.1093/cid/ciy234] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Accepted: 03/20/2018] [Indexed: 08/08/2023] Open
Abstract
BACKGROUND The epidemiology of acute hepatitis A and E has been changing over the last 2 decades. The impact of concomitant chronic hepatitis B (CHB) on clinical outcomes remains unclear. We aimed to evaluate the morbidity and mortality of patients with acute hepatitis A or E with and without underlying CHB. METHODS We identified consecutive patients with acute hepatitis A or E based on hepatitis serology from the electronic medical records of the Hospital Authority of Hong Kong from January 2000 to December 2016. Hepatic events, all-cause mortality, and liver-related mortality within 30 days of the diagnosis of acute hepatitis were evaluated. RESULTS The cohort included 1068 cases of acute hepatitis A and 846 cases of acute hepatitis E. More patients with acute hepatitis E than those with acute hepatitis A had underlying CHB (13.5% vs 8.0%; P < .001). Patients with hepatitis E had more all-cause mortality (3.9% vs 0.6%; P < .001), liver-related mortality (2.0% vs 0.3%; P < .001), and hepatic events (2.8% vs 0.3%; P < .001) within 30 days from diagnosis. In patients with acute hepatitis E, underlying renal failure (adjusted hazard ratio [aHR], 3.90; P < .001) and age ≥50 years (aHR, 3.25; P = .036) were associated with 30-day all-cause mortality, whereas CHB (aHR, 3.34; P = .02) was associated with 30-day liver-related mortality. CONCLUSIONS The mortality is higher in patients with acute hepatitis E than in those with hepatitis A. Coexisting CHB is the independent risk factor for liver-related mortality in patients with acute hepatitis E.
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Affiliation(s)
- Jimmy Che-To Lai
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
- Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
- State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Terry Cheuk-Fung Yip
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
- Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Yee-Kit Tse
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
- Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Kelvin Long-Yan Lam
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
- Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Grace Chung-Yan Lui
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Henry Lik-Yuen Chan
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
- Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
- State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
- Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
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Frias M, López-López P, Rivero A, Rivero-Juarez A. Role of Hepatitis E Virus Infection in Acute-on-Chronic Liver Failure. BIOMED RESEARCH INTERNATIONAL 2018; 2018:9098535. [PMID: 30050945 PMCID: PMC6046156 DOI: 10.1155/2018/9098535] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 06/06/2018] [Indexed: 12/11/2022]
Abstract
Chronic liver disease (CLD) with a variety of causes is currently reported to be one of the main causes of death worldwide. Patients with CLD experience deteriorating liver function and fibrosis, progressing to cirrhosis, chronic hepatic decompensation (CHD), end-stage liver disease (ESLD), and death. Patients may develop acute-on-chronic liver failure (ACLF), typically related to a precipitating event and associated with increased mortality. The objective of this review was to analyze the role of acute hepatitis E virus (HEV) infection in patients with CLD, focusing on the impact of this infection on patient survival and prognosis in several world regions.
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Affiliation(s)
- Mario Frias
- Clinical Virology and Zooneses, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Spain
| | - Pedro López-López
- Clinical Virology and Zooneses, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Spain
| | - Antonio Rivero
- Clinical Virology and Zooneses, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Spain
| | - Antonio Rivero-Juarez
- Clinical Virology and Zooneses, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Spain
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Abstract
Acute on chronic liver failure (ACLF) was first described in 1995 as a clinical syndrome distinct to classic acute decompensation. Characterized by complications of decompensation, ACLF occurs on a background of chronic liver dysfunction and is associated with high rates of organ failure and significant short-term mortality estimated between 45% and 90%. Despite the clinical relevance of the condition, it still remains largely undefined with continued disagreement regarding its precise etiological factors, clinical course, prognostic criteria and management pathways. It is concerning that, despite our relative lack of understanding of the condition, the burden of ACLF among cirrhotic patients remains significant with an estimated prevalence of 30.9%. This paper highlights our current understanding of ACLF, including its etiology, diagnostic and prognostic criteria and pathophysiology. It is evident that further refinement of the ACLF classification system is required in order to detect high-risk patients and improve short-term mortality rates. The field of metabolomics certainly warrants investigation to enhance diagnostic and prognostic parameters, while the use of granulocyte-colony stimulating factor is a promising future therapeutic intervention for patients with ACLF.
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Affiliation(s)
- Azeem Alam
- Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, SW7 2AZ, UK
| | - Ka Chun Suen
- Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, SW7 2AZ, UK
| | - Daqing Ma
- Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, SW7 2AZ, UK
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Zhang S, Chen C, Peng J, Li X, Zhang D, Yan J, Zhang Y, Lu C, Xun J, Li W, Ling Y, Huang Y, Chen L. Investigation of underlying comorbidities as risk factors for symptomatic human hepatitis E virus infection. Aliment Pharmacol Ther 2017; 45:701-713. [PMID: 28078736 DOI: 10.1111/apt.13938] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Revised: 06/16/2016] [Accepted: 12/21/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Symptomatic Hepatitis E virus (HEV) infection occurs in few infected subjects, and the risk factors are not completely known. AIM To explore the risk factors for adverse clinical outcomes in acute HEV infections. METHODS A large retrospective study was conducted. The baseline characteristics, clinical outcomes, and laboratory data of 512 acute HEV infection cases were analysed using logistic regression models. RESULTS All patients exhibited autochthonous sporadic HEV infections, and most were elderly. Their symptoms varied from asymptomatic to severe liver diseases. In all, 215 patients (42.0%) had liver failure and/or decompensation, and 45 (8.2%) patients died within 3 months. Nearly 60% of patients had underlying chronic liver diseases (CLDs), 20% were cirrhotic, and various extrahepatic underlying comorbidities were common. The logistic regression analysis revealed that underlying CLDs, especially cirrhosis, were closely associated with disease severity (OR = 8.78, P < 0.001) but not with mortality in patients with severe liver diseases. In addition to the known factors, including an old age, the male gender and CLDs, we identified pre-existing extrahepatic tumours, diabetes, and chronic respiratory and renal diseases as novel independent predictors for adverse clinical outcomes. Importantly, patients without these four extrahepatic comorbidities showed a much lower mortality rate (4.2%, P < 0.001) than patients with one (18.5%) or more comorbidities (34.5%). CONCLUSIONS Previous comorbidities, including tumours, diabetes, and chronic liver, lung and kidney diseases, were independent risk factors for adverse outcomes, especially mortality, in acute HEV infections. This study provides valuable data for improving the prevention and control of HEV infection.
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Affiliation(s)
- S Zhang
- Shanghai Public Health Clinical center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.,Key Laboratory of Medical Molecular Virology of Ministries of Education/Health, Institute of Medical Microbiology, Shanghai Medical College of Fudan University, Shanghai, China
| | - C Chen
- Department of Hepatology, Shanghai Public Clinical center, Fudan University, Shanghai, China.,Wenzhou Medical University, Wenzhou, Zhejiang
| | - J Peng
- Shanghai Public Health Clinical center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
| | - X Li
- Department of Hepatology, Shanghai Public Clinical center, Fudan University, Shanghai, China
| | - D Zhang
- Department of Hepatology, Shanghai Public Clinical center, Fudan University, Shanghai, China
| | - J Yan
- Shanghai Public Health Clinical center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
| | - Y Zhang
- Shanghai Public Health Clinical center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.,School of Life Sciences, Hebei Normal University, Shi-Jiazhuang, Hebei
| | - C Lu
- Department of Hepatology, Shanghai Public Clinical center, Fudan University, Shanghai, China
| | - J Xun
- Shanghai Public Health Clinical center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.,School of Life Sciences, Hebei Normal University, Shi-Jiazhuang, Hebei
| | - W Li
- Department of Hepatology, Shanghai Public Clinical center, Fudan University, Shanghai, China
| | - Y Ling
- Department of Hepatology, Shanghai Public Clinical center, Fudan University, Shanghai, China
| | - Y Huang
- Department of Hepatology, Shanghai Public Clinical center, Fudan University, Shanghai, China
| | - L Chen
- Department of Hepatology, Shanghai Public Clinical center, Fudan University, Shanghai, China
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Chen C, Zhang SY, Zhang DD, Li XY, Zhang YL, Li WX, Yan JJ, Wang M, Xun JN, Lu C, Ling Y, Huang YX, Chen L. Clinical features of acute hepatitis E super-infections on chronic hepatitis B. World J Gastroenterol 2016; 22:10388-10397. [PMID: 28058019 PMCID: PMC5175251 DOI: 10.3748/wjg.v22.i47.10388] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Revised: 11/01/2016] [Accepted: 11/16/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B (CHB) superimposed with hepatitis E virus (HEV).
METHODS This retrospective cohort study included 228 patients with acute HEV infection (showing clinical acute hepatitis symptomology and positivity for anti-HEV immunoglobulin M) with underlying CHB (confirmed by positivity for hepatitis B surface antigen and/or hepatitis B virus (HBV) DNA over 6 mo) who had been admitted to the Shanghai Public Health Clinical Center, which represents the regional tertiary hospital for infectious diseases in Shanghai city, China. Data for adverse outcomes were collected, and included severe liver diseases (defined as liver failure and/or acute liver decompensation) and liver-related mortality. Logistic regression modeling was performed to determine the risk factors for adverse outcomes.
RESULTS The symptoms caused by superimposed acute hepatitis E (AHE) were much more severe in cirrhotic patients (n = 94) than in non-cirrhotic patients (n = 134), as evidenced by significantly higher liver complications (77.7% vs 28.4%, P < 0.001) and mortality rate (21.3% vs 7.5%, P = 0.002). Most of the cirrhotic patients (n = 85, 90.4%) had no prior decompensation. Among the non-cirrhotic patients, superimposed AHE caused progressively more severe diseases that corresponded with the CHB disease stages, from immune tolerant to immune reactivation phases. Few risk factors were identified in the cirrhotic patients, but risk factors for non-cirrhotic patients were found to be intermediate HBV DNA levels (OR: 5.1, P = 0.012), alcohol consumption (OR: 6.4, P = 0.020), and underlying diabetes (OR: 7.5, P = 0.003) and kidney diseases (OR: 12.7, P = 0.005). Only 28.7% of the cirrhotic patients and 9.0% of the non-cirrhotic patients had received anti-HBV therapy previously and, in all cases, the efficacy had been suboptimal.
CONCLUSION CHB-related cirrhosis and intermediate HBV DNA level were associated with severe disease in superinfected patients, and successful antiviral treatment might counter this outcome.
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Abstract
Acute-on-chronic liver failure (ACLF) is a distinct entity that differs from acute liver failure and decompensated cirrhosis in timing, presence of treatable acute precipitant, and course of disease, with a potential for self-recovery. The core concept is acute deterioration of existing liver function in a patient of chronic liver disease with or without cirrhosis in response to an acute insult. The insult should be a hepatic one and presentation in the form of liver failure (jaundice, encephalopathy, coagulopathy, ascites) with or without extrahepatic organ failure in a defined time frame. ACLF is characterized by a state of deregulated inflammation. Initial cytokine burst presenting as SIRS, progression to CARS and associated immunoparalysis leads to sepsis and multi-organ failure. Early identification of the acute insult and mitigation of the same, use of nucleoside analogue in HBV-ACLF, steroid in severe alcoholic hepatitis, steroid in severe autoimmune hepatitis and/or bridging therapy lead to recovery, with a 90-day transplant-free survival rate of up to 50 %. First-week presentation is crucial concerning SIRS/sepsis, development, multiorgan failure and consideration of transplant. A protocol-based multi-disciplinary approach including critical care hepatology, early liver transplant before multi-organ involvement, or priority for organ allocation may improve the outcome. Presentation with extrahepatic organ involvement or inclusion of sepsis as an acute insult in definition restricts the therapy, i.e., liver transplant or bridging therapy, and needs serious consideration. Augmentation of regeneration, cell-based therapy, immunotherapy, and gut microbiota modulation are the emerging areas and need further research.
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Affiliation(s)
- Shiv Kumar Sarin
- Department of Hepatology and Liver Transplant, Institute of Liver and Biliary Sciences, D-1, VasantKunj, New Delhi, 110070, India.
| | - Ashok Choudhury
- Department of Hepatology and Liver Transplant, Institute of Liver and Biliary Sciences, D-1, VasantKunj, New Delhi, 110070, India
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Abstract
Acute-on-chronic liver failure (ACLF) is a distinct clinical entity and differs from acute liver failure and decompensated cirrhosis in timing, presence of acute precipitant, course of disease and potential for unaided recovery. The definition involves outlining the acute and chronic insults to include a homogenous patient group with liver failure and an expected outcome in a specific timeframe. The pathophysiology of ACLF relates to persistent inflammation, immune dysregulation with initial wide-spread immune activation, a state of systematic inflammatory response syndrome and subsequent sepsis due to immune paresis. The disease severity and outcome can be predicted by both hepatic and extrahepatic organ failure(s). Clinical recovery is expected with the use of nucleoside analogues for hepatitis B, and steroids for severe alcoholic hepatitis and, possibly, severe autoimmune hepatitis. Artificial liver support systems help remove toxins and metabolites and serve as a bridge therapy before liver transplantation. Hepatic regeneration during ongoing liver failure, although challenging, is possible through the use of growth factors. Liver transplantation remains the definitive treatment with a good outcome. Pre-emptive antiviral agents for hepatitis B before chemotherapy to prevent viral reactivation and caution in using potentially hepatotoxic drugs can prevent the development of ACLF.
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Affiliation(s)
- Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110070, India
| | - Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110070, India
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Shimakawa Y, Njai HF, Takahashi K, Berg L, Ndow G, Jeng-Barry A, Ceesay A, Tamba S, Opoku E, Taal M, Akbar SMF, Arai M, D'Alessandro U, Taylor-Robinson SD, Njie R, Mishiro S, Thursz MR, Lemoine M. Hepatitis E virus infection and acute-on-chronic liver failure in West Africa: a case-control study from The Gambia. Aliment Pharmacol Ther 2016; 43:375-384. [PMID: 26623967 DOI: 10.1111/apt.13484] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Revised: 09/17/2015] [Accepted: 11/04/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND In sub-Saharan Africa, it is unknown whether hepatitis E virus (HEV) infection is a common precipitating event of acute-on-chronic liver failure (ACLF). AIMS To estimate the prevalence of HEV infection in general population and assess whether HEV is a common trigger of ACLF in cirrhotic patients in The Gambia, West Africa. METHODS We first conducted an HEV sero-survey in healthy volunteers. We then tested cirrhotic patients with ACLF (cases) and compensated cirrhosis (controls) for anti-HEV IgG as a marker of exposure to HEV, and anti-HEV IgA and HEV RNA as a marker of recent infection. We also described the characteristics and survival of the ACLF cases and controls. RESULTS In the healthy volunteers (n = 204), 13.7% (95% CI: 9.6-19.2) were positive for anti-HEV IgG, and none had positive HEV viraemia. After adjusting for age and sex, the following were associated with positive anti-HEV IgG: being a Christian, a farmer, drinking water from wells, handling pigs and eating pork. In 40 cases (median age: 45 years, 72.5% male) and 71 controls (39 years, 74.6% male), ≥70% were infected with hepatitis B virus. Although hepatitis B flare and sepsis were important precipitating events of ACLF, none had marker of acute HEV. ACLF cases had high (70.0%) 28-day mortality. CONCLUSIONS Hepatitis E virus infection is endemic in The Gambia, where both faecal-oral route (contaminated water) and zoonotic transmission (pigs/pork meat) may be important. However, acute HEV was not a common cause of acute-on-chronic liver failure in The Gambia.
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Affiliation(s)
- Y Shimakawa
- MRC Unit The Gambia, Banjul, The Gambia
- Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France
| | - H F Njai
- MRC Unit The Gambia, Banjul, The Gambia
| | - K Takahashi
- Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan
| | - L Berg
- MRC Unit The Gambia, Banjul, The Gambia
- Hepatology Unit, Department of Medicine, Imperial College London, London, UK
| | - G Ndow
- MRC Unit The Gambia, Banjul, The Gambia
- Hepatology Unit, Department of Medicine, Imperial College London, London, UK
| | | | - A Ceesay
- MRC Unit The Gambia, Banjul, The Gambia
| | - S Tamba
- MRC Unit The Gambia, Banjul, The Gambia
| | - E Opoku
- MRC Unit The Gambia, Banjul, The Gambia
- Hepatology Unit, Department of Medicine, Imperial College London, London, UK
| | - M Taal
- Ministry of Health and Social Welfare, Banjul, The Gambia
| | - S M F Akbar
- Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan
| | - M Arai
- Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan
| | | | - S D Taylor-Robinson
- Hepatology Unit, Department of Medicine, Imperial College London, London, UK
| | - R Njie
- MRC Unit The Gambia, Banjul, The Gambia
- The Gambia Hepatitis Intervention Study, IARC, c/o MRC Unit, Banjul, The Gambia
| | - S Mishiro
- Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan
| | - M R Thursz
- Hepatology Unit, Department of Medicine, Imperial College London, London, UK
| | - M Lemoine
- MRC Unit The Gambia, Banjul, The Gambia
- Hepatology Unit, Department of Medicine, Imperial College London, London, UK
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Fu J, Guo D, Gao D, Huang W, Li Z, Jia B. Clinical analysis of patients suffering from chronic hepatitis B superinfected with other hepadnaviruses. J Med Virol 2015; 88:1003-9. [PMID: 26509653 DOI: 10.1002/jmv.24417] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/22/2015] [Indexed: 12/14/2022]
Abstract
To compare the clinical manifestations, laboratory examinations, and prognoses of patients with chronic hepatitis B (CHB) who were superinfected with hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV), or hepatitis E virus (HEV). Two hundred and eleven patients with confirmed CHB in our hospital, a tertiary teaching hospital in China, between 2005 and 2014 were analyzed retrospectively. Among 211 patients with CHB, 35 were superinfected with HAV, 31 were superinfected with HCV, 22 were superinfected with HDV, and 53 were superinfected with HEV. We analyzed and compared the clinical features of the five groups. The tested biochemical indices and markers of liver function included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), prothrombin activity (PTA), serum albumin (Alb), and the serum levels of HBV DNA. The peak values of ALT, AST, and TBil were significantly higher in all of the superinfected groups. Lower peak Alb concentration and PTA were also observed in the superinfected patients, with the exception of patients in the CHB + HAV group. The CHB + HCV, and CHB + HEV groups had higher death rates than the CHB monoinfected group, and the difference was statistically significant. Further analysis of the liver failure groups showed that the level of HBV DNA was not correlated with prognosis. The comparison of clinical outcomes revealed that CHB patients superinfected with HCV, HDV, and HEV compared with CHB monoinfection had statistically greater incidences of exacerbation of the condition and poor prognosis, whereas the patients superinfected with HAV generally had better outcomes.
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Affiliation(s)
- Jia Fu
- Key Laboratory of Infectious and Parasitic Diseases in Chongqing, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dan Guo
- Key Laboratory of Infectious and Parasitic Diseases in Chongqing, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dandan Gao
- Key Laboratory of Infectious and Parasitic Diseases in Chongqing, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wenxiang Huang
- Key Laboratory of Infectious and Parasitic Diseases in Chongqing, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ziqiong Li
- Key Laboratory of Infectious and Parasitic Diseases in Chongqing, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Bei Jia
- Key Laboratory of Infectious and Parasitic Diseases in Chongqing, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Schulz M, Schott E. An unusual cause for a hepatic flare in a chronic HBV carrier. HEPATITIS MONTHLY 2014; 14:e20099. [PMID: 25386198 PMCID: PMC4221959 DOI: 10.5812/hepatmon.20099] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/09/2014] [Revised: 08/26/2014] [Accepted: 08/29/2014] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Hepatitis E is an emerging disease in developed countries with an increasing incidence. In developed countries, HEV genotype 3 prevails as a zoonotic disease carried by wild boars or pigs, which usually causes asymptomatic infection. CASE PRESENTATION An asymptomatic HBsAg carrier was tested regularly at a German university hospital and showed no signs of chronic hepatitis B (CHB) activity. At a routine visit, elevated aminotransferases were detected while HBV DNA remained low and the patient was clinically asymptomatic. The laboratory signs of acute hepatitis resolved spontaneously. When aminotransferases returned to normal limits, the patient showed a flare of HBV-replication, which resolved spontaneously. In follow-up, further investigations revealed a resolved hepatitis E (HEV) superinfection causing an acute hepatitis before the HBV flare. No potential risk factors for HEV infection were identified. CONCLUSIONS Elevated aminotransferases in CHB patients are most commonly caused by exacerbation of CHB. Nevertheless, when HBV DNA is not elevated, other reasons should be excluded. Amongst others, superinfection with another hepatotropic virus can be the reason for decompensation of chronic hepatitis B. This case report describes an asymptomatic HEV superinfection followed by a flare in HBV replication in an HBsAg carrier without signs of HBV replication for eight years. In CHB carriers with signs of acute hepatitis, rare causes should be considered as well. HEV should be a part of routine laboratory evaluation for hepatitis flares given the rising number of infections.
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Affiliation(s)
- Marten Schulz
- Department of Hepatology and Gastroenterology, Charite Universitätsmedizin Berlin, Berlin, Germany
| | - Eckart Schott
- Department of Hepatology and Gastroenterology, Charite Universitätsmedizin Berlin, Berlin, Germany
- Corresponding Author: Eckart Schott, Department of Hepatology and Gastroenterology, Charite Universitätsmedizin Berlin, 13353, Berlin, Germany. Tel: +49-30450553199, Fax: +49-30450553903, E-mail:
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Srivastava A, Mathias A, Yachha SK, Agarwal J, Aggarwal R. Need for immunization against hepatotropic viruses in children with chronic liver disease. J Pediatr Gastroenterol Nutr 2014; 59:393-7. [PMID: 24840513 DOI: 10.1097/mpg.0000000000000437] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OBJECTIVES Infection with hepatotropic viruses is a common cause of acute deterioration and adverse outcome in children with chronic liver disease (CLD). Such superimposed infections may be preventable through vaccination. The present study aimed to evaluate the exposure rates of hepatitis A, B, and E viruses in children with CLD and suggest an optimal vaccination strategy. METHODS Children with CLD were prospectively evaluated with a demographic, clinical, and investigative proforma. Hepatitis B surface antigen positive cases were labeled as hepatitis B virus-CLD, and all other etiologies as non-HBV-related CLD. Patients were tested for exposure to hepatitis A (total anti-hepatitis A virus [HAV], immunoglobulin M anti-HAV), hepatitis B (hepatitis B surface antigen, total anti-hepatitis B core, anti-hepatitis B surface), and hepatitis E (IgG anti-hepatitis E virus). RESULTS A total of 142 children with CLD (age 9.1 ± 3.7 years, 83 [58.5%] boys) were enrolled. A total of 3.5% (5/142) and 38.7% (55/142) had received HAV and HBV vaccines, respectively. A total of 134 (94.4%) were total anti-HAV positive including 5 postimmunization patients, with higher positivity in those older than 5 years (19/25 vs 115/117; P = 0.001). Of the 115 patients with non-HBV-related CLD, 45 (39.1%) had exposure to HBV (40 total anti-hepatitis B core positive and 5 anti-HBs positive without immunization). Only 28 of 142 (19.7%) patients were IgG anti-HEV positive, with no difference across age. CONCLUSIONS A total of 90.8%, 39.1%, and 19.7% of children with CLD from the developing world are exposed to hepatitis A, B, and E infections, respectively. Selective hepatitis A vaccination (patients younger than 5 years of age) and universal hepatitis B vaccination are required to protect children with CLD. Sanitation improvement and HEV vaccine trial are needed for prevention against HEV.
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Affiliation(s)
- Anshu Srivastava
- *Departments of Pediatric Gastroenterology †Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
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Jalan R, Yurdaydin C, Bajaj JS, Acharya SK, Arroyo V, Lin HC, Gines P, Kim WR, Kamath PS. Toward an improved definition of acute-on-chronic liver failure. Gastroenterology 2014; 147:4-10. [PMID: 24853409 DOI: 10.1053/j.gastro.2014.05.005] [Citation(s) in RCA: 221] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Rajiv Jalan
- Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, UK
| | - Cihan Yurdaydin
- Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - Subrat K Acharya
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Vicente Arroyo
- Liver Unit, Hospital Clínic, University of Barcelona, Ciber de Enfermedades Hepaticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
| | - Han-Chieh Lin
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Pere Gines
- Liver Unit, Hospital Clínic, University of Barcelona, Ciber de Enfermedades Hepaticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
| | - W Ray Kim
- Division of Gastroenterology and Hepatology, Stanford University Medical School, Palo Alto, California
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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Chow CW, Tsang SWC, Tsang OTY, Leung VKS, Fung KSC, Luk WK, Chau TN. Comparison of acute hepatitis E infection outcome in patients with and without chronic hepatitis B infection: a 10 year retrospective study in three regional hospitals in Hong Kong. J Clin Virol 2014; 60:4-10. [PMID: 24646686 DOI: 10.1016/j.jcv.2014.01.024] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2013] [Revised: 12/27/2013] [Accepted: 01/27/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND Acute hepatitis E virus (HEV) infection has recently become the commonest cause of acute viral hepatitis in Hong Kong (HK) with majority of HEV belonging to genotype 4. Studies from China have shown that acute hepatitis E patients with underlying chronic hepatitis B virus (HBV) infection may have a worse outcome than those without. In India where genotype 1 is more prevalent, superinfection with hepatitis E on patients with chronic liver disease including chronic hepatitis B infection can cause liver decompensation. OBJECTIVES The study aims to determine the clinical outcome of acute hepatitis E infection in patients with and without chronic hepatitis B infection in HK. STUDY DESIGN The rates of liver failure, liver-related mortality and all-cause mortality will be compared between acute hepatitis E patients with and without chronic hepatitis B. Analysis was performed using the Statistical Package for the Social Science (SPSS version 12.0). All statistical tests were two-sided, and statistical significance was taken as p<0.05. RESULTS Chronic HBV carriers with acute HEV infection were found to have higher liver failure rate, liver-related mortality and all-cause mortality, but the results did not reach statistical significance. Chronic HBV carriers were found to have statistically significantly lower admission ALT level, lower day 28 serum albumin level and higher day 28 serum ALT level. CONCLUSIONS A prospective study with sufficient sample size is needed to confirm whether the clinical outcome of patients with chronic HBV infection is worse compared with patients who were not chronic HBV carriers.
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Affiliation(s)
- Chi-Wing Chow
- Department of Medicine, Tseung Kwan O Hospital, Hong Kong Special Administrative Region.
| | | | - Owen Tak-Yin Tsang
- Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region
| | - Vincent King-Sun Leung
- Department of Medicine and Geriatrics, United Christian Hospital, Hong Kong Special Administrative Region
| | - Kitty Sau-Chun Fung
- Department of Pathology, United Christian Hospital, Hong Kong Special Administrative Region
| | - Wei-Kwang Luk
- Department of Clinical Pathology, Tseung Kwan O Hospital, Hong Kong Special Administrative Region
| | - Tai-Nin Chau
- Department of Medicine and Geriatrics, United Christian Hospital, Hong Kong Special Administrative Region
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Agrawal S, Dhiman RK. Hepatobiliary quiz-8 (2013). J Clin Exp Hepatol 2013; 3:357-61. [PMID: 25755526 PMCID: PMC4216931 DOI: 10.1016/j.jceh.2013.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
| | - Radha K. Dhiman
- Address for correspondence: Radha K. Dhiman, Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
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Kumar A, Saraswat VA. Hepatitis E and Acute-on-Chronic Liver Failure. J Clin Exp Hepatol 2013; 3:225-30. [PMID: 25755504 PMCID: PMC3940130 DOI: 10.1016/j.jceh.2013.08.013] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2013] [Accepted: 08/26/2013] [Indexed: 12/12/2022] Open
Abstract
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis (AVH) globally. It causes large scale epidemics of AVH across the low- and middle income countries in Asia and Africa, and also causes sporadic cases of AVH in the same geographical region. AVH due to HEV is usually an acute, self-limiting illness, similar in clinical presentation to AVH caused by hepatitis A virus (HAV). When HEV causes AVH in patients of chronic liver disease it may worsen rapidly to a syndrome called acute-on-chronic liver failure (ACLF) leading to very high mortality. Acute deterioration of liver function in a patient with compensated chronic liver disease is the characteristic feature of ACLF. The typical disease course of patients with ACLF is the appearance of organ failure, which progresses to multi-organ failure and death. Many publications have reported HEV as one of the leading causes for ACLF from Asia and Africa, where HEV is endemic. The mortality rate of HEV-related ACLF (HEV-ACLF) ranges from 0% to 67% with a median being 34%. These patients require admission in the intensive care unit and they benefit from a team approach of clinicians with expertise in both hepatology and critical care. The goals of treatment are to prevent further deterioration in liver function, reverse precipitating factors, and support failing organs. Liver transplantation is required in selected patients to improve survival and quality of life. One preliminary report suggests that ribavirin may be an effective and safe drug for treatment of HEV-ACLF however this requires validation in large trials.
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Key Words
- ACLF, acute-on-chronic liver failure
- APASL, Asia–Pacific Association for the Study of Liver
- AVH, acute viral hepatitis
- CHB, chronic hepatitis B
- HAV, hepatitis A virus
- HBV, hepatitis B virus
- HEV, hepatitis E virus
- HEV-ACLF, HEV-related ACLF
- ICU, intensive care unit
- INR, international normalized ratio
- MELD, model for end-stage liver disease
- acute-on-chronic liver failure
- cirrhosis
- hepatitis E virus
- liver failure
- ribavirin
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Affiliation(s)
- Ashish Kumar
- Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi 110 060, India,Address for correspondence: Ashish Kumar, Associate Professor & Consultant Hepatologist, Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi 110 060, India. Tel.: +91 9312792573.
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh 226014, India
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Kaba M, Moal V, Gérolami R, Colson P. Epidemiology of mammalian hepatitis E virus infection. Intervirology 2013; 56:67-83. [PMID: 23343760 DOI: 10.1159/000342301] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2011] [Accepted: 07/28/2012] [Indexed: 12/26/2022] Open
Abstract
Mammalian hepatitis E virus (HEV), the etiological agent of hepatitis E in humans, is a recently discovered infectious agent. It was identified for the first time in 1983 using electron microscopy on a faecal specimen of a person infected with non-A, non-B enterically-transmitted hepatitis. Based on retrospective and prospective studies, HEV was long described as one of the leading causes of acute viral hepatitis in tropical and subtropical countries, whereas in developed countries hepatitis E was considered an imported disease from HEV hyperendemic countries. Data from studies conducted during the past decade have greatly shifted our knowledge on the epidemiology and clinical spectrum of HEV. Recently, it has been shown that contrary to previous beliefs, hepatitis E is also an endemic disease in several developed countries, particularly in Japan and in Europe, as evidenced by reports of high anti-HEV immunoglobulin G prevalence in healthy individuals and an increasing number of non-travel-related acute hepatitis E cases. Moreover, a porcine reservoir and growing evidence of zoonotic transmission have been reported in these countries. This review summarizes the current knowledge on the epidemiology and prevention of transmission of mammalian HEV.
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Affiliation(s)
- Mamadou Kaba
- Aix-Marseille Université, URMITE UM63 CNRS 7278 IRD 198 INSERM U1095, IHU Méditerranée Infection, Facultés de Médecine et de Pharmacie, Marseille, France
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Abstract
Acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB) is most commonly caused by acute severe exacerbation of CHB. The pathophysiology of ACLF in CHB is still poorly understood. Despite the identification of important predisposing factors and prognostic markers, ACLF in CHB remains a disease associated with high mortality. The majority of studies using nucleoside analog therapy did not show any significant improvement in survival, although larger prospective studies are needed. Liver transplantation is the definitive treatment for ACLF in CHB. The challenge ahead would be prognosticating cases with favorable or unfavorable outcomes in order to streamline patients for early transplantation or for medical therapy.
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Affiliation(s)
- Wai-Kay Seto
- Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong
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Geng JB, Wang MR, Wang L, Wang J, Yang ZG, Cheng Y, Qiao F, Wang M. Genetic characteristics and pathogenicity of human hepatitis E virus in Nanjing, China. World J Gastroenterol 2012; 18:965-70. [PMID: 22408357 PMCID: PMC3297057 DOI: 10.3748/wjg.v18.i9.965] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2011] [Revised: 11/10/2011] [Accepted: 12/16/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the genetic characteristics and pathogenicity of hepatitis E virus (HEV) and assess the potential risk factors for sporadic hepatitis E.
METHODS: Sixty-two serum samples from the patients with acute hepatitis E were collected, including 23 cases coinfected with hepatitis B virus. Anti-HEV detection and partial HEV RNA amplification were performed by enzyme immunoassays and reverse transcription-nested polymerase chain reaction (RT-nPCR) method, respectively, and PCR products were sequenced. The isolated human HEV sequences were analyzed phylogenetically.
RESULTS: The positive rate of serum HEV RNA were 21.0% (13/62), including 5 cases of liver failure. All the 13 isolates shared a 82.1%-98.0% nucleotide homology with each other and had identities of 74.7%-81.0%, 75.3%-78.6%, 75.3%-80.0% and 82.1%-96.1% with the corresponding regions of HEV genotypes 1-4, respectively. The human HEV strain GS-NJ-12 shared a 100% nucleotide identity with the swine HEV strain swIM6-43 isolated from Inner Mongolia, China.
CONCLUSION: Swine may be a principal risk factor for occurrence of sporadic hepatitis E in eastern China, and genotype 4 HEV can induce acute liver failure.
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Fan XF, Yu FJ, Li XF, Dong PH, Chen YP, Li J. ANALYSIS OF 111 CASES OF HEPATITIS E IN OLDER ADULTS IN CHINA: 1997-2010. J Am Geriatr Soc 2011; 59:1770-1. [DOI: 10.1111/j.1532-5415.2011.03577.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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