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Zhang D, Chen Z, Wu J, Ning N, Chen L, Tian X. Chemotherapy-induced febrile neutropenia followed by acute hepatitis E virus infection in rectal cancer patient with synchronous liver and lung metastasis: a case report. BMC Infect Dis 2025; 25:693. [PMID: 40361031 PMCID: PMC12070571 DOI: 10.1186/s12879-025-11097-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 05/08/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) typically induces self-limiting infection but can establish persistent infection, particularly in patients with compromised immune systems. However, the literature on HEV infection in patients undergoing chemotherapy is limited. CASE PRESENTATION A 46-year-old Chinese male patient with rectal cancer underwent ten cycles of chemotherapy and targeted therapy. Routine blood tests revealed grade 4 bone marrow suppression necessitating emergency admission. On the second day following admission, the patient presented with high fever that was determined to be chemotherapy-induced febrile neutropenia (FN). However, despite the recovery of white blood cell counts, the fever persisted, and the levels of aminotransferases and bilirubin continued to rise. Two weeks after admission, next generation sequencing of blood samples revealed evidence of HEV. The patient underwent symptomatic and supportive treatment and was discharged after a 30-day hospitalization. One month after discharge, the transaminase and bilirubin levels were within the normal range. DISCUSSION The fatality rate of FN is alarmingly high. To prevent progression to sepsis syndrome and potential mortality, it is imperative to initiate empirical treatment with broad-spectrum antibiotics. As the differential diagnosis of elevated liver enzymes in immunocompromised patients encompasses a wide range of possibilities, the exclusion of HEV infection is crucial when diagnosing drug-induced liver injury (DILI). CONCLUSION This case highlights the importance of healthcare providers being vigilant in identifying HEV infection in patients with solid tumors who experience FN and DILI. Early implementation of comprehensive supportive treatment is crucial for reducing the duration of disease and enhancing patient prognosis.
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Affiliation(s)
- Dongdong Zhang
- Peking University First School of Clinical Medicine, Peking University First Hospital, Beijing, People's Republic of China
- Department of Gastrointestinal Surgery, Peking University International Hospital, Beijing, People's Republic of China
| | | | - Jixiang Wu
- Department of Gastrointestinal Surgery, Peking University International Hospital, Beijing, People's Republic of China
| | - Ning Ning
- Department of Gastrointestinal Surgery, Peking University International Hospital, Beijing, People's Republic of China
| | - Lin Chen
- Department of Gastrointestinal Surgery, Peking University International Hospital, Beijing, People's Republic of China
| | - Xiaodong Tian
- Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, No.8 Xishiku Street, Xicheng District, Beijing, 100034, People's Republic of China.
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2
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Church RJ, Anchang B, Bennett BD, Bushel PR, Watkins PB. Blood toxicogenomics reveals potential biomarkers for management of idiosyncratic drug-induced liver injury. Front Genet 2025; 16:1524433. [PMID: 40201567 PMCID: PMC11975945 DOI: 10.3389/fgene.2025.1524433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 03/04/2025] [Indexed: 04/10/2025] Open
Abstract
Introduction: Accurate diagnosis, assessment, and prognosis of idiosyncratic drug-induced liver injury (IDILI) is problematic, in part due to the shortcomings of traditional blood biomarkers. Studies in rodents and healthy volunteers have supported that RNA transcript changes in whole blood may address some of these shortcomings. Methods: In this study, we conducted RNA-Seq analysis on peripheral blood samples collected from 55 patients with acute IDILI and 17 patients with liver injuries not attributed to IDILI. Results and discussion: Three differentially expressed genes (DEGs; CFD, SQLE, and INKA1) were identified as significantly associated with IDILI vs. other liver injuries. No DEGs were identified comparing IDILI patients to the 5 patients with autoimmune hepatitis, suggesting possible common underlying mechanisms. Two genes (VMO1 and EFNA1) were significantly associated with hepatocellular injury compared to mixed/cholestatic injury. When patients with severe vs. milder IDILI were compared, we identified over 500 DEGs. The top pathways identified from these DEGs had in common down regulation of multiple T-cell specific genes. Further analyses confirmed that these changes could largely be accounted for by a fall in the concentration of circulating T-cells during severe DILI, perhaps due to exhaustion or sequestration of these cells in the liver. Exploration of DEGs specific for the individual causal agents was largely unsuccessful, but isoniazid-induced IDILI demonstrated 25 DEGs compared to other non-isoniazid IDILI cases. Finally, among the 14 IDILI patients that had hepatocellular jaundice (i.e., Hy's Law cases), we identified 39 DEGs between the 4 patients with fatal or liver transplantation outcomes compared to those that recovered. These findings suggest the potential for blood-based transcriptomic biomarkers to aid in the diagnosis and prognostic stratification of IDILI.
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Affiliation(s)
- Rachel J. Church
- Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC, United States
| | - Benedict Anchang
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States
| | - Brian D. Bennett
- Integrative Bioinformatics Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States
| | - Pierre R. Bushel
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States
| | - Paul B. Watkins
- Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC, United States
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Blake EM, Byers KA, Lee MJ, Cao J, Layne C, Borlang J, Huynh D, Andonov A, Kuchinski KS, Lynch J, Robinson SJ, Nicol AM, Himsworth CG. Rat Hepatitis E Virus Isolates Cluster among Urban Norway Rats (Rattus norvegicus) across a Roadway. J Wildl Dis 2025; 61:192-198. [PMID: 39522549 DOI: 10.7589/jwd-d-24-00052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Accepted: 09/26/2024] [Indexed: 11/16/2024]
Abstract
Hepatitis E virus (HEV) is a globally distributed pathogen that causes acute hepatitis in people. Recent human cases of HEV arising after contact with urban rats (Rattus spp.) have raised concerns regarding whether rats may be a source of HEV infection. We investigated whether urban Norway rats (Rattus norvegicus) could be a source of HEV in an underserved urban neighborhood of Vancouver, Canada. We found that 15% of rats tested positive for rat HEV, and that HEV status was associated with increasing rat body length and family relationships. Rat HEV isolates were clustered according to their location on either the east or west side of a busy roadway bisecting this neighborhood, suggesting that this street is a barrier to HEV spread. Widespread distribution of HEV among rats in this neighborhood poses potential human health risks, emphasizing the need to reduce close contact of people with rats and their excreta.
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Affiliation(s)
- Elly M Blake
- Faculty of Health Sciences, Simon Fraser University, 8888 University Drive West, Burnaby, British Columbia V5A1S6, Canada
| | - Kaylee A Byers
- Faculty of Health Sciences, Simon Fraser University, 8888 University Drive West, Burnaby, British Columbia V5A1S6, Canada
- Canadian Wildlife Health Cooperative, Animal Health Centre, British Columbia Ministry of Agriculture, 1767 Angus Campbell Road, Abbotsford, British Columbia V3G2M3, Canada
| | - Michael Joseph Lee
- Canadian Wildlife Health Cooperative, Animal Health Centre, British Columbia Ministry of Agriculture, 1767 Angus Campbell Road, Abbotsford, British Columbia V3G2M3, Canada
- School of Population and Public Health, University of British Columbia, 2206 E Mall, Vancouver, British Columbia V6T1Z3, Canada
| | - Jingxin Cao
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3R2, Canada
| | - Christine Layne
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3R2, Canada
| | - Jamie Borlang
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3R2, Canada
| | - Denise Huynh
- Canadian Food Inspection Agency, 1015 Arlington Street, Winnipeg, Manitoba, R3E 3R2, Canada
| | - Anton Andonov
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3R2, Canada
- Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
| | - Kevin S Kuchinski
- British Columbia Centre for Disease Control, Pathology and Laboratory Medicine, 655 W 12th Avenue, Vancouver, British Columbia V5Z 4R4, Canada
| | - Jessie Lynch
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3R2, Canada
| | - Sarah J Robinson
- Faculty of Health Sciences, Simon Fraser University, 8888 University Drive West, Burnaby, British Columbia V5A1S6, Canada
| | - Anne-Marie Nicol
- Faculty of Health Sciences, Simon Fraser University, 8888 University Drive West, Burnaby, British Columbia V5A1S6, Canada
| | - Chelsea G Himsworth
- Canadian Wildlife Health Cooperative, Animal Health Centre, British Columbia Ministry of Agriculture, 1767 Angus Campbell Road, Abbotsford, British Columbia V3G2M3, Canada
- School of Population and Public Health, University of British Columbia, 2206 E Mall, Vancouver, British Columbia V6T1Z3, Canada
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McSteen BW, Ying XH, Lucero C, Jesudian AB. Viral etiologies of acute liver failure. World J Virol 2024; 13:97973. [PMID: 39323454 PMCID: PMC11401000 DOI: 10.5501/wjv.v13.i3.97973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 08/07/2024] [Accepted: 08/19/2024] [Indexed: 08/29/2024] Open
Abstract
Acute liver failure (ALF) is a rare cause of liver-related mortality worldwide, with an estimated annual global incidence of more than one million cases. While drug-induced liver injury, including acetaminophen toxicity, is the leading cause of ALF in the Western world, viral infections remain a significant cause of ALF and the most common cause in many developing nations. Given the high mortality rates associated with ALF, healthcare providers should be aware of the broad range of viral infections that have been implicated to enable early diagnosis, rapid treatment initiation when possible, and optimal management, which may include liver transplantation. This review aims to provide a summary of viral causes of ALF, diagnostic approaches, treatment options, and expected outcomes.
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Affiliation(s)
- Brian W McSteen
- Department of Medicine, New York-Presbyterian/Weill Cornell Campus, New York, NY 10021, United States
| | - Xiao-Han Ying
- Department of Medicine, New York-Presbyterian/Weill Cornell Campus, New York, NY 10021, United States
| | - Catherine Lucero
- Department of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10021, United States
| | - Arun B Jesudian
- Department of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10021, United States
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5
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Müller SL, Kaumanns A, Adam KM, Osthoff M, Dräger S. Misdiagnosed Antibiotic-Induced Liver Injury: Unveiling Acute Hepatitis E in a 65-Year-Old Patient. AMERICAN JOURNAL OF CASE REPORTS 2024; 25:e944508. [PMID: 39182163 PMCID: PMC11361320 DOI: 10.12659/ajcr.944508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 07/17/2024] [Accepted: 06/29/2024] [Indexed: 08/27/2024]
Abstract
BACKGROUND Common causes of severely elevated transaminases, especially alanine transaminase, due to liver diseases include drug-induced liver injury and acute viral hepatitis, especially hepatitis E, which can present similarly in clinical practice. Broad differential diagnostic workup in patients with elevated transaminases is required to not overlook the possibility of hepatitis E infection. CASE REPORT We report on a 65-year-old asymptomatic man who was referred to the Emergency Department from the rehabilitation center due to markedly elevated liver transaminases. Physical examination revealed no jaundice or abdominal pain. Laboratory findings included severely elevated aspartate transaminase, alanine transaminase, and bilirubin levels. He was previously treated with imipenem/cilastatin and clindamycin for a surgical site infection of his jaw after the removal of a squamous cell carcinoma 2 weeks earlier. An ultrasound of the liver was unremarkable. Drug-induced liver injury was suspected, and all potentially hepatotoxic drugs, including antibiotics, were stopped. Due to the rapid and marked increase in liver transaminases, further tests were performed, including testing for hepatitis E. Serum anti-hepatitis E virus immunoglobulin M, immunoglobulin G antibodies, and hepatitis E virus-ribonucleic acid-polymerase chain reaction turned positive, and the diagnosis of hepatitis E was confirmed. Supportive care was applied. Liver transaminases decreased spontaneously. CONCLUSIONS The diagnostic workup in patients with markedly elevated liver transaminases and suspected drug-induced liver injury should include the screening for hepatitis E. Making the correct diagnosis is crucial given the differing treatment approaches, the implications on further therapy, and the risk of contagion of hepatitis E.
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Affiliation(s)
| | - Anna Kaumanns
- Division of Internal Medicine, University Hospital Basel, Basel, Switzerland
| | - Kai-Manuel Adam
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
| | - Michael Osthoff
- Division of Internal Medicine, University Hospital Basel, Basel, Switzerland
- Department of Clinical Research, University of Basel, Basel, Switzerland
| | - Sarah Dräger
- Division of Internal Medicine, University Hospital Basel, Basel, Switzerland
- Department of Clinical Research, University of Basel, Basel, Switzerland
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6
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Yadav KK, Boley PA, Khatiwada S, Lee CM, Bhandari M, Kenney SP. Development of fatty liver disease model using high cholesterol and low choline diet in white leghorn chickens. Vet Res Commun 2024; 48:2489-2497. [PMID: 38861204 PMCID: PMC11315703 DOI: 10.1007/s11259-024-10420-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 05/17/2024] [Indexed: 06/12/2024]
Abstract
Nonalcoholic fatty liver disease (NAFLD), which shows similar symptoms as fatty liver hemorrhage syndrome (FLHS) in chickens, is the most common cause of chronic liver disease and cancer in humans. NAFLD patients and FLHS in chickens have demonstrated severe liver disorders when infected by emerging strains of human hepatitis E virus (HEV) and avian HEV, respectively. We sought to develop a fatty liver disease chicken model by altering the diet of 3-week-old white leghorn chickens. The high cholesterol, and low choline (HCLC) diet included 7.6% fat with additional 2% cholesterol and 800 mg/kg choline in comparison to 5.3% fat, and 1,300 mg/kg choline in the regular diet. Our diet induced fatty liver avian model successfully recapitulates the clinical features seen during NAFLD in humans and FLHS in chickens, including hyperlipidemia and hepatic steatosis, as indicated by significantly higher serum triglycerides, serum cholesterol, liver triglycerides, cholesterol, and fatty acids. By developing this chicken model, we expect to provide a platform to explore the role of lipids in the liver pathology linked with viral infections and contribute to the development of prophylactic interventions.
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Affiliation(s)
- Kush Kumar Yadav
- Center for Food Animal Health (CFAH), Department of Animal Sciences, The Ohio State University, 1680 Madison Ave, Wooster, OH, 44691, USA
- Department of Veterinary Preventive Medicine, The Ohio State University, Columbus, OH, 43210, USA
| | - Patricia A Boley
- Center for Food Animal Health (CFAH), Department of Animal Sciences, The Ohio State University, 1680 Madison Ave, Wooster, OH, 44691, USA
| | - Saroj Khatiwada
- Center for Food Animal Health (CFAH), Department of Animal Sciences, The Ohio State University, 1680 Madison Ave, Wooster, OH, 44691, USA
| | - Carolyn M Lee
- Center for Food Animal Health (CFAH), Department of Animal Sciences, The Ohio State University, 1680 Madison Ave, Wooster, OH, 44691, USA
- Department of Veterinary Preventive Medicine, The Ohio State University, Columbus, OH, 43210, USA
| | - Menuka Bhandari
- Center for Food Animal Health (CFAH), Department of Animal Sciences, The Ohio State University, 1680 Madison Ave, Wooster, OH, 44691, USA
| | - Scott P Kenney
- Center for Food Animal Health (CFAH), Department of Animal Sciences, The Ohio State University, 1680 Madison Ave, Wooster, OH, 44691, USA.
- Department of Veterinary Preventive Medicine, The Ohio State University, Columbus, OH, 43210, USA.
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7
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Gibbens Y, Lake J, Lim N. A Rare Cause of Acute Liver Failure. Gastroenterology 2024; 167:446-449. [PMID: 38331206 DOI: 10.1053/j.gastro.2024.01.048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 01/18/2024] [Accepted: 01/23/2024] [Indexed: 02/10/2024]
Affiliation(s)
- Ying Gibbens
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, Minnesota
| | - John Lake
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, Minnesota
| | - Nicholas Lim
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, Minnesota.
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Kaplan DE, Ripoll C, Thiele M, Fortune BE, Simonetto DA, Garcia-Tsao G, Bosch J. AASLD Practice Guidance on risk stratification and management of portal hypertension and varices in cirrhosis. Hepatology 2024; 79:1180-1211. [PMID: 37870298 DOI: 10.1097/hep.0000000000000647] [Citation(s) in RCA: 116] [Impact Index Per Article: 116.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 10/16/2023] [Indexed: 10/24/2023]
Affiliation(s)
- David E Kaplan
- Department of Medicine, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA USA
| | - Cristina Ripoll
- Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Maja Thiele
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Brett E Fortune
- Department of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | | | - Jaime Bosch
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
- Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) and CIBERehd, University of Barcelona, Spain
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9
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Ahmed T, Ahmad J. Recent advances in the diagnosis of drug-induced liver injury. World J Hepatol 2024; 16:186-192. [PMID: 38495272 PMCID: PMC10941738 DOI: 10.4254/wjh.v16.i2.186] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 01/03/2024] [Accepted: 02/03/2024] [Indexed: 02/27/2024] Open
Abstract
Drug-induced liver injury (DILI) is a major problem in the United States, commonly leading to hospital admission. Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between drug exposure and liver injury and a thorough work up for other causes. In addition, DILI has a very variable clinical and histologic presentation that can mimic many different etiologies of liver disease. Objective scoring systems can assess the probability that a drug caused the liver injury but liver biopsy findings are not part of the criteria used in these systems. This review will address some of the recent updates to the scoring systems and the role of liver biopsy in the diagnosis of DILI.
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Affiliation(s)
- Taqwa Ahmed
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
| | - Jawad Ahmad
- Department of Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
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10
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Dong R, Chang D, Luo Z, Zhang M, Guan Q, Shen C, Chen Y, Huang P, Wang J. The burden of HEV-related acute liver failure in Bangladesh, China and India: a systematic review and meta-analysis. BMC Public Health 2023; 23:2369. [PMID: 38031080 PMCID: PMC10688087 DOI: 10.1186/s12889-023-17302-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 11/22/2023] [Indexed: 12/01/2023] Open
Abstract
BACKGROUND Hepatitis E can potentially progress to HEV-related acute liver failure (HEV-ALF). East and South Asia bear a substantial burden of HEV infection, with Bangladesh, China, and India facing the most severe threat in this region. Therefore, we conducted a systematic review and meta-analysis to evaluate the burden of HEV-ALF in these three high-risk countries. METHODS A systematic literature search was performed utilizing PubMed, the Cochrane Library, Medline, Embase, and Web of Science databases. Studies in English or Chinese that reported data on the burden of HEV-ALF in Bangladesh, China and India were included. Outcomes were pooled with meta-analysis utilizing R software. Estimates were calculated with random-effects models, and subgroup analysis and sensitivity analysis were conducted to address heterogeneity. Egger's test and Begg's test were performed to assess publication bias. RESULTS A total of 20 eligible studies were included in this study. The pooled HEV-attributable proportion of viral-related acute liver failure was estimated to be 40.0% (95% CI: 0.28-0.52), 30.0% (95% CI: 0.18-0.44), and 61.0% (95% CI: 0.49-0.72) among non-pregnant individuals in India, China and Bangladesh, while in Indian pregnant females, it was 71.0% (95% CI: 0.62-0.79). The combined prevalence among non-pregnant HEV-infected participants was 28.0% (95% CI: 0.20-0.37) and 10.0% (95% CI: 0.01-0.28) in India and China, and it was 34.0% (95% CI: 0.27-0.42) in Indian pregnant females with HEV infection. The overall mortality of HEV-ALF was estimated to be 32.0% (95% CI: 0.23-0.42) and 64.0% (95% CI: 0.50-0.77) among the non-pregnant and the pregnant participants in India, and it was 23.0% (95% CI: 0.14-0.34) in Chinese non-pregnant participants. CONCLUSIONS The burden of HEV-ALF in Bangladesh, China, and India is non-negligible despite geographic and population heterogeneity. The prevention of HEV infection and early recognition of HEV-ALF are of great significance, especially in high-risk countries and populations. REGISTRATION PROSPERO registration ID is CRD42022382101.
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Affiliation(s)
- Rui Dong
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, Jiangsu, China
| | - Dongchun Chang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, Jiangsu, China
| | - Zhenghan Luo
- East China Institute of Biomedical Technology, Nanjing, China
| | - Mengting Zhang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, Jiangsu, China
| | - Qing Guan
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, Jiangsu, China
| | - Chao Shen
- Nanjing Municipal Center for Disease Control and Prevention, Nanjing, China
| | - Yue Chen
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, Jiangsu, China
| | - Peng Huang
- Department of Epidemiology, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, Jiangsu, China.
| | - Jie Wang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, Jiangsu, China.
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11
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Rafique Q, Rehman A, Afghan MS, Ahmad HM, Zafar I, Fayyaz K, Ain Q, Rayan RA, Al-Aidarous KM, Rashid S, Mushtaq G, Sharma R. Reviewing methods of deep learning for diagnosing COVID-19, its variants and synergistic medicine combinations. Comput Biol Med 2023; 163:107191. [PMID: 37354819 PMCID: PMC10281043 DOI: 10.1016/j.compbiomed.2023.107191] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 05/28/2023] [Accepted: 06/19/2023] [Indexed: 06/26/2023]
Abstract
The COVID-19 pandemic has necessitated the development of reliable diagnostic methods for accurately detecting the novel coronavirus and its variants. Deep learning (DL) techniques have shown promising potential as screening tools for COVID-19 detection. In this study, we explore the realistic development of DL-driven COVID-19 detection methods and focus on the fully automatic framework using available resources, which can effectively investigate various coronavirus variants through modalities. We conducted an exploration and comparison of several diagnostic techniques that are widely used and globally validated for the detection of COVID-19. Furthermore, we explore review-based studies that provide detailed information on synergistic medicine combinations for the treatment of COVID-19. We recommend DL methods that effectively reduce time, cost, and complexity, providing valuable guidance for utilizing available synergistic combinations in clinical and research settings. This study also highlights the implication of innovative diagnostic technical and instrumental strategies, exploring public datasets, and investigating synergistic medicines using optimised DL rules. By summarizing these findings, we aim to assist future researchers in their endeavours by providing a comprehensive overview of the implication of DL techniques in COVID-19 detection and treatment. Integrating DL methods with various diagnostic approaches holds great promise in improving the accuracy and efficiency of COVID-19 diagnostics, thus contributing to effective control and management of the ongoing pandemic.
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Affiliation(s)
- Qandeel Rafique
- Department of Internal Medicine, Sahiwal Medical College, Sahiwal, 57040, Pakistan.
| | - Ali Rehman
- Department of General Medicine Govt. Eye and General Hospital Lahore, 54000, Pakistan.
| | - Muhammad Sher Afghan
- Department of Internal Medicine District Headquarter Hospital Faislaabad, 62300, Pakistan.
| | - Hafiz Muhamad Ahmad
- Department of Internal Medicine District Headquarter Hospital Bahawalnagar, 62300, Pakistan.
| | - Imran Zafar
- Department of Bioinformatics and Computational Biology, Virtual University Pakistan, 44000, Pakistan.
| | - Kompal Fayyaz
- Department of National Centre for Bioinformatics, Quaid-I-Azam University Islamabad, 45320, Pakistan.
| | - Quratul Ain
- Department of Chemistry, Government College Women University Faisalabad, 03822, Pakistan.
| | - Rehab A Rayan
- Department of Epidemiology, High Institute of Public Health, Alexandria University, 21526, Egypt.
| | - Khadija Mohammed Al-Aidarous
- Department of Computer Science, College of Science and Arts in Sharurah, Najran University, 51730, Saudi Arabia.
| | - Summya Rashid
- Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj, 11942, Saudi Arabia.
| | - Gohar Mushtaq
- Center for Scientific Research, Faculty of Medicine, Idlib University, Idlib, Syria.
| | - Rohit Sharma
- Department of Rasashastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
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Takakusagi S, Kakizaki S, Takagi H. The Diagnosis, Pathophysiology, and Treatment of Chronic Hepatitis E Virus Infection-A Condition Affecting Immunocompromised Patients. Microorganisms 2023; 11:1303. [PMID: 37317277 PMCID: PMC10220693 DOI: 10.3390/microorganisms11051303] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 05/01/2023] [Accepted: 05/13/2023] [Indexed: 06/16/2023] Open
Abstract
Hepatitis E is a zoonosis caused by hepatitis E virus (HEV), which was first discovered 40 years ago. Twenty million HEV infections worldwide are estimated each year. Most hepatitis E cases are self-limiting acute hepatitis, but the virus has been recognized to cause chronic hepatitis. Following the first case report of chronic hepatitis E (CHE) in a transplant recipient, CHE has recently been identified as associated with chronic liver damage induced by HEV genotypes 3, 4, and 7-usually in immunocompromised patients such as transplant recipients. In addition, patients infected with HIV and those receiving chemotherapy for malignancy, along with patients with rheumatic disease and COVID-19, have recently been reported as having CHE. CHE can be easily misdiagnosed by usual diagnostic methods of antibody response, such as anti-HEV IgM or IgA, because of the low antibody response in the immunosuppressive condition. HEV RNA should be evaluated in these patients, and appropriate treatments-such as ribavirin-should be given to prevent progression to liver cirrhosis or liver failure. While still rare, cases of CHE in immunocompetent patients have been reported, and care must be taken not to overlook these instances. Herein, we conduct an overview of hepatitis E, including recent research developments and management of CHE, in order to improve our understanding of such cases. The early diagnosis and treatment of CHE should be performed to decrease instances of hepatitis-virus-related deaths around the world.
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Affiliation(s)
- Satoshi Takakusagi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22 Fujioka, Fujioka 375-0024, Gunma, Japan;
| | - Satoru Kakizaki
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki 370-0829, Gunma, Japan
| | - Hitoshi Takagi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22 Fujioka, Fujioka 375-0024, Gunma, Japan;
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13
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Okumura H, Miyamoto A, Suzuki F, Takaya H. Acute Hepatitis E Infection during Chemotherapy for Lung Cancer: A Case Report. Chemotherapy 2023; 68:155-159. [PMID: 37166305 DOI: 10.1159/000530802] [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: 12/31/2022] [Accepted: 04/17/2023] [Indexed: 05/12/2023]
Abstract
Acute hepatitis E, one of the causes of acute liver injury, has been increasingly diagnosed in developed countries in recent years. Misdiagnosis of acute hepatitis E virus (HEV) infection as drug-induced liver injury (DILI) may lead to discontinuation of effective chemotherapy. Thus, viral hepatitis, including hepatitis E, must be ruled out in the diagnosis of DILI. A 78-year-old woman with lung adenocarcinoma and multiple bone metastases received maintenance therapy with pemetrexed + pembrolizumab for a year. Increased aspartate aminotransferase and alanine aminotransferase levels, indicating acute liver injury, were observed. Initially, DILI was suspected, and she was given medications to lower the levels of hepatic enzymes. She was later admitted to the hospital with the chief complaint of general malaise and anorexia. Serum aspartate aminotransferase and alanine aminotransferase levels were markedly elevated (381 and 854 U/L, respectively). Acute HEV infection was diagnosed based on the detection of serum HEV immunoglobulin A antibodies. The patient received liver support therapy, and the serum hepatic enzymes recovered to normal levels. Chemotherapy was resumed without any subsequent relapse of hepatic enzyme elevation. When DILI is suspected during chemotherapy, exclusion of viral hepatitis is mandatory, which can be achieved by measuring markers of hepatitis viruses, including HEV, and examining the patient's detailed medical history.
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Affiliation(s)
- Hiroki Okumura
- Department of Respiratory Medicine, Toranomon Hospital (Branch), Kawasaki-shi, Japan
| | - Atsushi Miyamoto
- Department of Respiratory Medicine, Toranomon Hospital (Branch), Kawasaki-shi, Japan
- Department of Respiratory Medicine, Respiratory Centre, Toranomon Hospital, Minato-ku, Tokyo, Japan
| | - Fumitaka Suzuki
- Department of Hepatology, Toranomon Hospital, Minato-ku, Tokyo, Japan
| | - Hisashi Takaya
- Department of Respiratory Medicine, Toranomon Hospital (Branch), Kawasaki-shi, Japan
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14
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Fontana RJ, Liou I, Reuben A, Suzuki A, Fiel MI, Lee W, Navarro V. AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury. Hepatology 2023; 77:1036-1065. [PMID: 35899384 PMCID: PMC9936988 DOI: 10.1002/hep.32689] [Citation(s) in RCA: 78] [Impact Index Per Article: 39.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 07/07/2022] [Indexed: 12/14/2022]
Affiliation(s)
- Robert J. Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Iris Liou
- University of Washington, Seattle, Washington, USA
| | - Adrian Reuben
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Ayako Suzuki
- Division of Gastroenterology, Duke University, Durham, North Carolina, USA
| | - M. Isabel Fiel
- Department of Pathology, Mount Sinai School of Medicine, New York City, New York, USA
| | - William Lee
- Division of Gastroenterology, University of Texas Southwestern, Dallas, Texas, USA
| | - Victor Navarro
- Department of Medicine, Einstein Healthcare Network, Philadelphia, Pennsylvania, USA
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15
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Zhu L, Luo M, Zhang Y, Fang F, Li M, An F, Zhao D, Zhang J. Free radical as a double-edged sword in disease: Deriving strategic opportunities for nanotherapeutics. Coord Chem Rev 2023. [DOI: 10.1016/j.ccr.2022.214875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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16
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Samala N, Wang RY, Auh S, Balla AK, Dakhoul L, Alter HJ, Farci P, Ghabril M, Lucey MR, Rangnekar AS, Reddy KR, Ghany MG. Hepatitis E prevalence and infection in solid-organ transplant recipients in the United States. J Viral Hepat 2022; 29:1134-1142. [PMID: 36036116 DOI: 10.1111/jvh.13739] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 04/27/2022] [Accepted: 07/19/2022] [Indexed: 12/29/2022]
Abstract
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. An increased risk for HEV infection has been reported in organ-transplant recipients, mainly from Europe. Prospective data on HEV prevalence in the United States (U.S.) organ transplant population are limited. To determine the prevalence and factors associated with HEV infection among solid organ transplant-recipients, we conducted a prospective, cross-sectional, multicentre study among transplant-recipients and age- and organ-matched waitlist patients. Participants answered a risk-exposure questionnaire and were tested for HEV-RNA (in-house PCR), HEV-IgG, and IgM (ELISA, Wantai). Among 456 participants, 224 were transplant-recipients, and 232 were waitlist patients. The mean age was 58 years, 35% female, and 74% White. HEV seroprevalence of the entire cohort was 20.2% and associated with older age (p < 0.0001) and organ transplantation (p = 0.02). The HEV seropositivity was significantly higher among transplant-recipients compared with waitlist patients (24% vs. 16.4%, p = 0.042). Among transplant recipients, relative-risk of being HEV seropositive increased with older age (RR = 3.4 [1.07-10.74] in patients >70 years compared with ≤50 years, p = 0.037); history of graft hepatitis (2.2 [1.27-3.72], p = 0.005); calcineurin inhibitor use (RR = 1.9 [1.03-3.34], p = 0.02); and kidney transplantation (2.4 [1.15-5.16], p = 0.02). HEV-RNA, genotype 3 was detected in only two patients (0.4%), both transplant-recipients. HEV seroprevalence was higher among transplant-recipients than waitlist patients. HEV should be considered in transplant-recipients presenting with graft hepatitis. Detection of HEV-RNA was rare, suggesting that progression to chronic HEV infection is uncommon in transplant-recipients in the U.S.
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Affiliation(s)
- Niharika Samala
- Division of Gastroenterology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Richard Y Wang
- Department of Transfusion Medicine, National Institutes of Health, Bethesda, Maryland, USA
| | - Sungyoung Auh
- Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Abdalla Kara Balla
- MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - Lara Dakhoul
- Division of Gastroenterology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Harvey J Alter
- Department of Transfusion Medicine, National Institutes of Health, Bethesda, Maryland, USA
| | - Patrizia Farci
- Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Marwan Ghabril
- Division of Gastroenterology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Michael R Lucey
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Amol S Rangnekar
- MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
| | - K Rajender Reddy
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Marc G Ghany
- Liver Disease Branch (LDB), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
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17
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Sayed IM, Abdelwahab SF. Is Hepatitis E Virus a Neglected or Emerging Pathogen in Egypt? Pathogens 2022; 11:1337. [PMID: 36422589 PMCID: PMC9697431 DOI: 10.3390/pathogens11111337] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 11/04/2022] [Accepted: 11/08/2022] [Indexed: 09/02/2023] Open
Abstract
Though Egypt ranks among the top countries for viral hepatitis and death-related liver disease, Hepatitis E virus (HEV) is a neglected pathogen. Living in villages and rural communities with low sanitation, use of underground well water and contact with animals are the main risk factors for HEV infection. Domestic animals, especially ruminants and their edible products, are one source of infection. Contamination of water by either human or animal stools is the main route of infection. In addition, HEV either alone or in coinfection with other hepatotropic viruses has been recorded in Egyptian blood donors. HEV seropositivity among Egyptian villagers was 60-80%, especially in the first decade of life. Though HEV seropositivity is the highest among Egyptians, HEV infection is not routinely diagnosed in Egyptian hospitals. The initial manifestations of HEV among Egyptians is a subclinical infection, although progression to fulminant hepatic failure has been recorded. With the improvement in serological and molecular approaches and increasing research on HEV, it is becoming clear that HEV represents a threat for Egyptians and preventive measures should be considered to reduce the infection rate and possible complications.
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Affiliation(s)
- Ibrahim M. Sayed
- Department of Biomedical and Nutritional Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Sayed F. Abdelwahab
- Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
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18
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Yan T, Sakai Y, Terada K, Okano S, Kawasaki S, Kashiwagi T, Iwabu M. A Case of Hepatitis E Virus Infection: One of Differential Diagnosis of Liver Injury in Patients Undergoing Peritoneal Dialysis. Int Med Case Rep J 2022; 15:557-561. [PMID: 36245962 PMCID: PMC9562814 DOI: 10.2147/imcrj.s385393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 10/06/2022] [Indexed: 11/17/2022] Open
Abstract
Background There are numerous causes of liver function disorder in patients undergoing peritoneal dialysis (PD). Infection with the Hepatitis E virus (HEV) is a rare cause of liver injury, and the behavior of HEV in patients with PD is unclear. Since patients undergoing dialysis are frequently polypharmatic, liver injury caused by HEV infection may be misdiagnosed as drug-induced liver injury. Case Presentation A 61-year-old woman with PD developed abrupt elevation of blood transaminase levels on a routine outpatient session. Since the patient has been receiving tolvaptan as the only new medication, we suspected tolvaptan induced liver injury. In further investigating the cause of liver injury, the blood screening test was found to be positive for HEV-IgA. The patient was diagnosed with HEV infection, and had a self-limited course. Conclusion When encountered with patients developing liver injury during PD, HEV infection should be included in the differential diagnosis.
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Affiliation(s)
- Tomohiro Yan
- Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Yukinao Sakai
- Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan,Correspondence: Yukinao Sakai, Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan, Tel +81-03-3822-2131, Fax +81-3-3822-4865, Email
| | - Kohsuke Terada
- Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Sho Okano
- Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Sayuri Kawasaki
- Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Tetsuya Kashiwagi
- Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Masato Iwabu
- Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
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19
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Fontana RJ, Engle RE, Hayashi PH, Gu J, Kleiner DE, Nguyen H, Barnhart H, Hoofnagle JH, Farci P. Incidence of Hepatitis E Infection in American Patients With Suspected Drug-Induced Liver Injury Is Low and Declining: The DILIN Prospective Study. Am J Gastroenterol 2022; 117:1462-1470. [PMID: 35973149 PMCID: PMC9437122 DOI: 10.14309/ajg.0000000000001869] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 06/07/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Hepatitis E virus (HEV) infection rarely causes icteric hepatitis, yet 10%-40% of adult Americans have serological evidence of previous infection. The aim of this study was to investigate the incidence, presentation, and outcome of acute and previous HEV infection in a large cohort of patients with suspected drug-induced liver injury (DILI). METHODS Serum samples from 2012 patients enrolled in the DILI Network were tested for anti-HEV immunoglobulin G (IgG). Those with detectable anti-HEV IgG underwent testing for anti-HEV IgM; those with detectable anti-HEV immunoglobulin m (IgM) were tested for HEV RNA. RESULTS Anti-HEV IgG was detected in 407 (20%) patients and associated with increasing subject age and earlier year of enrollment. The median age of seropositive subjects was more than a decade higher than seronegative subjects (59.8 vs 48.7 years). The overall prevalence of anti-HEV declined from 22% (2004-2011) to 18% (2012-2019), suggestive of a cohort effect. The frequency of acute hepatitis E (median ALT = 1231 IU/L) also decreased from 3% (2004-2008) to 1.2% (2009-2013) to 0.6% (2014-2019). These results suggest that acute HEV infection is usually subclinical and was much more frequent in this cohort before 2004. DISCUSSION Acute HEV infection accounts for less than 1% of suspected American DILI cases and is more frequent in older men. Previous HEV infection is also most commonly seen in older individuals. Clinicians should consider testing for unsuspected acute HEV infection in older adult patients with acute hepatocellular DILI and jaundice.
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Affiliation(s)
- Robert John Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Ronald E Engle
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - Paul H Hayashi
- Food and Drug Administration, Silver Spring, Maryland, USA
| | - Jiezhun Gu
- Duke Clinical Research Institute, Durham, North Carolina, USA
| | - David E Kleiner
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Hahn Nguyen
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - Huiman Barnhart
- Duke Clinical Research Institute, Durham, North Carolina, USA
| | - Jay H Hoofnagle
- Department of Medicine, Ohio State University, Columbus, Ohio, USA
- National Institute of Diabetes and Digestive and Kidney-Diseases, Bethesda, Maryland, USA
| | - Patrizia Farci
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
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20
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Plüß M, Tampe D, Schwörer H, Bremer SCB, Tampe B. Case report: Kinetics of human leukocyte antigen receptor HLA-DR during liver injury induced by potassium para-aminobenzoate as assessed for causality using the updated RUCAM. Front Pharmacol 2022; 13:966910. [PMID: 36059975 PMCID: PMC9428317 DOI: 10.3389/fphar.2022.966910] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 07/25/2022] [Indexed: 11/13/2022] Open
Abstract
Potassium para-aminobenzoate (POTABA) is used to treat Peyronie’s disease by decreasing fibrosis and plaque size progression. Among potential side effects, drug-induced liver injury (DILI) attributed to POTABA administration has been reported in a few cases and inferred to immune hypersensitivity. In the present case, we investigated clinical, biochemical, and serological features as well as searched for non-drug-related causes, and applied the updated Roussel Uclaf Causality Assessment Method (RUCAM) confirming a highly probable causality of POTABA-induced liver injury. Moreover, we here observed specific activated CD3+ T lymphocytes during the acute phase of liver injury by monitoring of human leukocyte antigen receptor (HLA-DR) expression. Furthermore, improvement of biochemical markers of liver injury after POTABA withdrawal was associated with a rapid decline of CD3+ HLA-DR+ immune cells. In contrast, CD14+ monocytes expressing HLA-DR remained stable during recovery from liver injury. These observations implicate a specific involvement of activated T lymphocytes in liver injury mediated by POTABA. Clinicians should be aware of POTABA-induced liver injury, and measurement of activated immune cells by assessment of HLA-DR could provide pathomechanistic insights enabling biomonitoring of recovery from DILI.
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Affiliation(s)
- Marlene Plüß
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
| | - Désirée Tampe
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
| | - Harald Schwörer
- Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Göttingen, Göttingen, Germany
| | | | - Björn Tampe
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
- *Correspondence: Björn Tampe,
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21
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Damiris K, Aghaie Meybodi M, Niazi M, Pyrsopoulos N. Hepatitis E in immunocompromised individuals. World J Hepatol 2022; 14:482-494. [PMID: 35582299 PMCID: PMC9055194 DOI: 10.4254/wjh.v14.i3.482] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/15/2021] [Accepted: 02/12/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) originally identified as a cause of acute icteric hepatitis in developing countries has grown to be a cause of zoonotic viral hepatitis in developed countries such as the United States. While there are eight identified genotypes to date, genotype 1 (HEV1), HEV2, HEV3, HEV4 are the most common to infect humans. HEV1 and HEV2 are most common in developing countries including Latina America, Africa and Asia, and are commonly transmitted through contaminated water supplies leading to regional outbreaks. In contrast HEV3 and HEV4 circulate freely in many mammalian animals and can lead to occasional transmission to humans through fecal contamination or consumption of undercooked meat. The incidence and prevalence of HEV in the United States is undetermined given the absence of FDA approved serological assays and the lack of commercially available testing. In majority of cases, HEV infection is a self-limiting hepatitis requiring only symptomatic treatment. However, this is not the case in immunocompromised individuals, including those that have undergone solid organ or stem cell transplantation. In this subset of patients, chronic infection can be life threatening as hepatic insult can lead to inflammation and fibrosis with subsequent cirrhosis and death. The need for re-transplantation as a result of post-transplant hepatitis is of great concern. In addition, there have been many reported incidents of extrahepatic manifestations, for which the exact mechanisms remain to be elucidated. The cornerstone of treatment in immunocompromised solid organ transplant recipients is reduction of immunosuppressive therapies, while attempting to minimize the risk of organ rejection. Subsequent treatment options include ribavirin, and pegylated interferon alpha in those who have demonstrated ribavirin resistance. Further investigation assessing safety and efficacy of anti-viral therapy is imperative given the rising global health burden. Given this concern, vaccination has been approved in China with other investigations underway throughout the world. In this review we introduce the epidemiology, diagnosis, clinical manifestations, and treatment of HEV, with emphasis on immunocompromised individuals in the United States.
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Affiliation(s)
- Konstantinos Damiris
- Department of Medicine, Rutgers - New Jersey Medical School, Newark, NJ 07103, United States.
| | - Mohamad Aghaie Meybodi
- Department of Medicine, Rutgers - New Jersey Medical School, Newark, NJ 07103, United States
| | - Mumtaz Niazi
- Department of Medicine - Gastroenterology and Hepatology, Rutgers - New Jersey Medical School, Newark, NJ 07103, United States
| | - Nikolaos Pyrsopoulos
- Department of Medicine - Gastroenterology and Hepatology, Rutgers - New Jersey Medical School, Newark, NJ 07103, United States
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22
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Huang YS, Tseng SY, Chen WW, Chang TT, Peng CY, Lo GH, Hsu CW, Hu CT, Huang YH. Clinical characteristics and outcomes of drug-induced liver injury in Taiwan: With emphasis on the impact of chronic hepatitis B infection. J Chin Med Assoc 2022; 85:286-294. [PMID: 34698694 DOI: 10.1097/jcma.0000000000000648] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Whether hepatitis B virus (HBV) infection can affect the outcomes of drug-induced liver injury (DILI) is controversial. This study aimed to evaluate the characteristics and outcomes of DILI in Taiwan, with an emphasis on the impact of HBV infection. METHODS We prospectively recruited patients with DILI from multiple centers in Taiwan from 2010 to 2018. RESULTS A total of 1,014 patients were enrolled. The leading culprit drug category was antimicrobials (481, 47.4%), followed by nonsteroidal anti-inflammatory drugs, anticonvulsants, and statins. Among the antimicrobials, antituberculosis agents were most likely to induce liver injury (257, 25.3%), followed by antibacterial, antifungal, and antiviral agents. The liver-related mortality rate was 8.2% (83/1,014). The patients who died had higher rates of hepatocellular-type liver injury, elevated liver biochemical tests, preexisting liver cirrhosis, jaundice, chronic HBV infection, and antituberculosis drug-induced liver injury (ATDILI) than the survivors. A total of 131 patients (12.9%) with DILI were HBV carriers, of whom 23 (17.6%) died of hepatic failure. The rate of HBV-DNA > 2000 IU/mL was higher in the patients who died (47.8% vs. 26.9%, p = 0.047) than in the survivors. After adjusting for possible risk factors, active HBV infection with HBV-DNA > 2000 IU/mL was the most significant risk factor for liver-related mortality (adjusted HR, 4.40, 95% CI, 2.31%-8.38%, p < 0.001). The other independent risk factors for mortality were ATDILI and albumin-bilirubin (ALBI) score (adjusted HR, 1.25 and 4.09, respectively, p < 0.003). CONCLUSION Antituberculosis agents were the leading cause of DILI in Taiwanese, and they were associated with poorer outcomes than other drug categories. Active HBV infection, ATDILI and ALBI score were independent risk factors for fatal DILI. Close monitoring of liver tests and timely antiviral therapy should be implemented in HBV carriers during the administration of high-risk drugs, such as antituberculosis agents.
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Affiliation(s)
- Yi-Shin Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
| | - Shao-Yu Tseng
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
| | - Wen-Wen Chen
- Taiwan Drug Relief Foundation, Taipei, Taiwan, ROC
| | - Ting-Tsung Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
| | - Cheng-Yuan Peng
- Department of Internal Medicine, Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan, ROC
| | - Gin-Ho Lo
- Department of Medical Research, Digestive Center, E-DA Hospital, Kaohsiung, Taiwan, ROC
| | - Chao-Wei Hsu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Lin-Kou, Chang Gung University College of Medicine, Taoyuan, Taiwan, ROC
| | - Chi-Tan Hu
- Division of Gastroenterology and Hepatology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, ROC
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
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23
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Picchi G, Ricciardi A, Marola L, Di Norcia M, D'alessandro M, Mariani R, Cacciatore P, Sozio F, Necozione S, Cofini V, Parruti G, Villano U, Madonna E, Marcantonio C, Bruni R, Mataj E, Grimaldi A, Ciccaglione AR. Prevalence of HEV infection in acute non-ABC hepatitis and prognostic role of extrahepatic manifestations. LE INFEZIONI IN MEDICINA 2022; 31:70-78. [PMID: 36908387 PMCID: PMC9994827 DOI: 10.53854/liim-3101-10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 02/08/2023] [Indexed: 03/07/2023]
Abstract
Background HEV-3 and HEV-4 are emerging cause of zoonotic acute hepatitis in high-income countries. In Europe the disease is underdiagnosed but hyperendemic areas have been identified. We describe a population with acute non-ABC (n-ABC) hepatitis in Abruzzo, the Italian region with the highest seroprevalence reported. The study was included in the surveillance of acute hepatitis E by the Italian Institute of Public Health started in 2004 and implemented in 2015. Methods Patients with n-ABC hepatitis during 2004-2018 in all Abruzzo Infectious Disease Departments were tested for HEV-IgM (Wantai®) and HEV-RNA (ORF3). Positive samples were sequenced (Beckman Coulter®) and phylogenetic tree (MEGA 6.06 software) obtained. Clinical data were retrospectively collected and an alimentary risk factors-questionnaire was administered. Categorical and quantitative variables were compared (Chi square test or Fisher test and Wilcoxon test). Results 97 hospitalized patients were tested, most cases (91.7%) after 2015. Overall, HEV-IgM resulted positive in 36% and HEV-RNA detectable in 33.3%. All 24 sequences obtained were HEV-3, with two small groups of closely related strands. L'Aquila was the Province with higher positivity rate (44%). Retrospective clinical data were acquired in 86.5% of patients, no one having liver failure. Higher ALT-levels (1282.34 vs 893.25, p=0.0139) and extrahepatic symptoms (OR 16.69, p=0.0018) were strongly associated with HEV-IgM presence. Two small outbreaks are described. Conclusions More than one third of n-ABC hepatitis in all Abruzzo are HEV-related. Extrahepatic symptoms correlate with HEV aetiology. Implementing surveillance is mandatory to really understand the extent of the disease.
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Affiliation(s)
- Giovanna Picchi
- Infectious Diseases Department, Ospedale Regionale "San Salvatore", L'Aquila, Italy
| | - Alessandra Ricciardi
- Infectious Diseases Department, IRCCS Fondazione Policlinico "San Matteo", Pavia, Italy
| | - Lara Marola
- Department of Clinical Medicine, Life, Health & Environmental Sciences-MESVA, University of L'Aquila, Italy
| | - Monica Di Norcia
- Infectious Diseases Department, Ospedale Regionale "San Salvatore", L'Aquila, Italy
| | | | - Rinalda Mariani
- Infectious Disease Department, Ospedale Civile "SS. Nicola e Filippo", Avezzano, Italy
| | | | - Federica Sozio
- Infectious Disease Department, Ospedale "S. Spirito", Pescara, Italy
| | - Stefano Necozione
- Department of Clinical Medicine, Life, Health & Environmental Sciences-MESVA, University of L'Aquila, Italy
| | - Vincenza Cofini
- Department of Clinical Medicine, Life, Health & Environmental Sciences-MESVA, University of L'Aquila, Italy
| | - Giustino Parruti
- Infectious Disease Department, Ospedale "S. Spirito", Pescara, Italy
| | - Umbertina Villano
- Viral Hepatitis and Oncovirus and Retrovirus Diseases Unit, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Elisabetta Madonna
- Viral Hepatitis and Oncovirus and Retrovirus Diseases Unit, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Cinzia Marcantonio
- Viral Hepatitis and Oncovirus and Retrovirus Diseases Unit, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Roberto Bruni
- Viral Hepatitis and Oncovirus and Retrovirus Diseases Unit, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Elida Mataj
- Instituti i Shendetit Publik (ISHP), Tirana, Albania
| | - Alessandro Grimaldi
- Infectious Diseases Department, Ospedale Regionale "San Salvatore", L'Aquila, Italy
| | - Anna Rita Ciccaglione
- Viral Hepatitis and Oncovirus and Retrovirus Diseases Unit, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
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El-Mokhtar MA, Ramadan HKA, Thabet MM, Abd-Elkader AS, Fouad M, Sallam MM, Elgohary EA, Abd El-Hafeez AA, Mohamed ME, Sayed IM. The Unmet Needs of Hepatitis E Virus Diagnosis in Suspected Drug-Induced Liver Injury in Limited Resource Setting. Front Microbiol 2021; 12:737486. [PMID: 34690979 PMCID: PMC8533821 DOI: 10.3389/fmicb.2021.737486] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 09/06/2021] [Indexed: 12/27/2022] Open
Abstract
Background: Currently, there are no specific biomarkers for drug-induced liver injury (DILI), and the diagnosis of DILI is based mainly on the exclusion of other causes of liver dysfunction and the recognition of potential causative drugs. Hepatitis E virus (HEV) diagnosis is not routinely enrolled in many countries, and HEV infection could be misdiagnosed as DILI. Methodology: We retrospectively analyzed plasma samples (n = 80) collected from suspected DILI for HEV markers such as anti-HEV IgM, anti-HEV IgG, and HEV RNA. Anti-HEV antibodies were assessed using commercial ELISA kits. HEV RNA was tested by RT-qPCR targeting HEV ORF2/3, the receiver operating characteristic (ROC) curve was plotted, and a putative threshold for liver function parameters was determined. Results: Out of 80 samples, 12 samples were positive for anti-HEV IgM and anti-HEV IgG, and HEV RNA was detected in seven samples. The median viral load was 3.46 × 103 IU/ml, and the isolated viruses belonged to HEV genotype 1. The level of liver enzymes such as alanine transaminase (ALT) and aspartate transaminase (AST), but not alkaline phosphatase (ALP), was significantly higher in HEV confirmed cases than in non-HEV confirmed cases. We identified a plasma ALT level of at least 415.5 U/L and AST level of at least 332 U/L; ALT/ALP ratio of at least 5.08 could be used as a guide for the patients diagnosed as DILI to be tested for HEV infection. The previous liver function parameters showed high sensitivity and good specificity. Conclusion: Hepatitis E virus was detected in suspected DILI cases. The diagnosis of DILI is not secure until HEV testing is done. Liver function parameters can be used as a guide for HEV testing in suspected DILI cases in countries with limited resources.
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Affiliation(s)
- Mohamed A El-Mokhtar
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Asyut, Egypt.,Microbiology and Immunology Department, Faculty of Pharmacy, Sphinx University, Asyut, Egypt
| | - Haidi Karam-Allah Ramadan
- Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Asyut, Egypt
| | - Marwa M Thabet
- Department of Clinical pathology, Faculty of Medicine, Assiut University, Asyut, Egypt
| | - Alaa S Abd-Elkader
- Department of Clinical pathology, Faculty of Medicine, Assiut University, Asyut, Egypt
| | - Magdy Fouad
- Hepato-Gastroenterology Unit, Tropical Medicine Department, Faculty of Medicine, El-Minia University, Minya, Egypt
| | - Mohammad M Sallam
- Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Elsayed A Elgohary
- Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Amer Ali Abd El-Hafeez
- Pharmacology and Experimental Oncology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.,Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, CA, United States
| | - Mona Embarek Mohamed
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Asyut, Egypt
| | - Ibrahim M Sayed
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Asyut, Egypt
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Bessone F, Hernandez N, Tagle M, Arrese M, Parana R, Méndez-Sánchez N, Ridruejo E, Mendizabal M, Dagher L, Contreras F, Fassio E, Pessoa M, Brahm J, Silva M. Drug-induced liver injury: A management position paper from the Latin American Association for Study of the liver. Ann Hepatol 2021; 24:100321. [PMID: 33609753 DOI: 10.1016/j.aohep.2021.100321] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 01/18/2021] [Accepted: 01/18/2021] [Indexed: 02/06/2023]
Abstract
Idiosyncratic drug-induced liver injury (DILI) caused by xenobiotics (drugs, herbals and dietary supplements) is an uncommon cause of liver disease presenting with a wide range of phenotypes and disease severity, acute hepatitis mimicking viral hepatitis to autoimmune hepatitis, steatosis, fibrosis or rare chronic vascular syndromes. Disease severity ranges from asymptomatic liver test abnormalities to acute liver failure. DILI has been traditionally classified in predictable or intrinsic (dose-related) or unpredictable (not dose-related) mechanisms. Few prospective studies are assessing the real prevalence and incidence of hepatotoxicity in the general population. DILI registries represent useful networks used for the study of liver toxicity, aimed at improving the understanding of causes, phenotypes, natural history, and standardized definitions of hepatotoxicity. Although most of the registries do not carry out population-based studies, they may provide important data related to the prevalence of DILI, and also may be useful to compare features from different countries. With the support of the Spanish Registry of Hepatotoxicity, our Latin American Registry (LATINDILI) was created in 2011, and more than 350 DILI patients have been recruited to date. This position paper describes the more frequent drugs and herbs-induced DILI in Latin America, mainly focusing on several features of responsible medicaments. Also, we highlighted the most critical points on the management of hepatotoxicity in general and those based on findings from our Latin American experience in particular.
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Affiliation(s)
- Fernando Bessone
- Hospital Provincial del Centenario, Facultad de Medicina, Universidad Nacional de Rosario, Rosario, Argentina.
| | | | - Martin Tagle
- Universidad Peruana Cayetano Heredia, Lima, Peru
| | - Marco Arrese
- Pontificia Universidad Católica de chile, Santiago de Chile, Chile
| | | | - Nahum Méndez-Sánchez
- Liver Research Unit, Medica Sur Clinic & Foundation, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico; Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico
| | - Ezequiel Ridruejo
- Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno "CEMIC", Buenos Aires, Argentina
| | | | - Lucy Dagher
- Policlínica Metropolitana y CMDLT, Caracas, Venezuela
| | | | - Eduardo Fassio
- Hospital Nacional Prof. Alejandro Posadas, Provincia de Buenos Aires, Argentina
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Yao L, Nisar MF, Yan T, Wan C(C. Potential Effects of Dietary Isoflavones on Drug-Induced Liver Injury. J FOOD QUALITY 2021; 2021:1-10. [DOI: 10.1155/2021/2870969] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Numerous prescribed drugs and herbal and dietary supplements have been reported to cause drug-induced acute liver injury, which is a frequent cause of acute liver failure (ALF). It is a tremendous challenge with ever-increasing drug application in the medication system for huge populations. Drug-induced acute liver injury can lead to diverse pathologies similar to acute and chronic hepatitis, acute liver failure, biliary obstruction, fatty liver disease, and so on. Recently, extensive work demonstrated that isoflavones play an essential and protecting role in drug-induced liver injury (DILI). The isoflavones mediated hepatoprotection by modulating specific genes linked with control of cellular redox homeostasis and inflammatory responses. Isoflavones upregulate oxidative stress-responsive nuclear factor erythroid 2-like 2 (Nrf2), downregulate inflammatory nuclear factor-κB (NF-κB) signaling pathways, and modulate a balance between cell survival and death. Moreover, isoflavones actively inhibit the expression of cytochromes P450 (CYPs) enzyme during drug metabolism. Moreover, isoflavones are also linked with farnesoid X receptor (FXR) activation and signal transducer and activator of transcription factor 3 (STAT3) phosphorylation in hepatoprotection DILI. In vivo and in vitro studies clearly stated that isoflavones bear strong antioxidant potential and promising agents for hepatotoxicity prevention and stressed their potential role as therapeutic supplements in DILI. The current review will elaborate on isoflavones’ preventive and therapeutic potential concisely and highlight various molecular targets to exert a protective effect on DILI.
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Affiliation(s)
- Liangliang Yao
- Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330006, China
| | - Muhammad Farrukh Nisar
- Jiangxi Key Laboratory for Postharvest Technology and Nondestructive Testing of Fruits & Vegetables, College of Agronomy, Jiangxi Agricultural University, Nanchang 330045, China
- Department of Physiology and Biochemistry, Cholistan University of Veterinary and Animal Sciences (CUVAS), Bahawalpur 63100, Pakistan
| | - Tingdong Yan
- School of Pharmacy, Nantong University, Nantong 226019, China
| | - Chunpeng (Craig) Wan
- Jiangxi Key Laboratory for Postharvest Technology and Nondestructive Testing of Fruits & Vegetables, College of Agronomy, Jiangxi Agricultural University, Nanchang 330045, China
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Huang YS, Chang TT, Peng CY, Lo GH, Hsu CW, Hu CT, Huang YH. Herbal and dietary supplement-induced liver injury in Taiwan: comparison with conventional drug-induced liver injury. Hepatol Int 2021; 15:1456-1465. [PMID: 34382132 DOI: 10.1007/s12072-021-10241-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 07/20/2021] [Indexed: 10/25/2022]
Abstract
BACKGROUND AND AIMS Whether herbal and dietary supplements (HDS) are safer than Western conventional drugs is controversial. The aim of this study was to explore the characteristics and risk factors for HDS-induced liver injury (HILI) in Taiwan. METHODS This is a 9-year multi-center prospective study conducted in Taiwan from 2011 to 2019. Patients with HILI were compared to those with conventional drug-induced liver injury (CILI). RESULTS A total of 1,297 patients were enrolled, of whom 285 (22.0%) had HILI and 1,012 (78.0%) had CILI. Compared to the CILI group, the HILI group had higher initial serum alanine aminotransferase, alkaline phosphatase (ALP), peak ALP and bilirubin levels, and higher rates of jaundice, ascites, encephalopathy, coagulopathy, sepsis and acute liver failure. In addition, the HILI group had a higher mortality rate than the CILI group (12.6 vs. 8.0%, p = 0.016). Hepatitis B carrier status, elevated baseline liver biochemical tests and the use of crude herbs (without processing) were associated with an increased risk of HILI-related mortality (adjusted hazard ratios [95% confidence intervals]: 2.90 [1.43-5.99], 2.40 [1.01-5.68] and 2.94 [1.45-5.97], respectively). CONCLUSIONS HDS are popular and incriminated in more than one-fifth of drug-induced liver injuries in Taiwan. The patients with HILI were more severe than those with CILI in terms of liver biochemical tests, complications and mortality. Hepatitis B carriers, those with elevated baseline liver tests and crude herb users may have a higher risk of HILI-related mortality. The prudent use of HDS is suggested in these high-risk subjects.
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Affiliation(s)
- Yi-Shin Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, and National Yang Ming Chiao Tung University School of Medicine, 201, Section 2, Shi-Pai Road, Taipei, 11217, Taiwan.
| | - Ting-Tsung Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Cheng-Yuan Peng
- Department of Internal Medicine, Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Gin-Ho Lo
- Department of Medical Research, Digestive Center, E-DA Hospital, Kaohsiung, Taiwan
| | - Chao-Wei Hsu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Lin-Kou, and Chang Gung University College of Medicine, Lin-Kou, Taiwan
| | - Chi-Tan Hu
- Division of Gastroenterology and Hepatology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, and National Yang Ming Chiao Tung University School of Medicine, 201, Section 2, Shi-Pai Road, Taipei, 11217, Taiwan
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Boeckmans J, Rombaut M, Demuyser T, Declerck B, Piérard D, Rogiers V, De Kock J, Waumans L, Magerman K, Cartuyvels R, Rummens JL, Rodrigues RM, Vanhaecke T. Infections at the nexus of metabolic-associated fatty liver disease. Arch Toxicol 2021; 95:2235-2253. [PMID: 34027561 PMCID: PMC8141380 DOI: 10.1007/s00204-021-03069-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 04/29/2021] [Indexed: 02/07/2023]
Abstract
Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease that affects about a quarter of the world population. MAFLD encompasses different disease stadia ranging from isolated liver steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma. Although MAFLD is considered as the hepatic manifestation of the metabolic syndrome, multiple concomitant disease-potentiating factors can accelerate disease progression. Among these risk factors are diet, lifestyle, genetic traits, intake of steatogenic drugs, male gender and particular infections. Although infections often outweigh the development of fatty liver disease, pre-existing MAFLD could be triggered to progress towards more severe disease stadia. These combined disease cases might be underreported because of the high prevalence of both MAFLD and infectious diseases that can promote or exacerbate fatty liver disease development. In this review, we portray the molecular and cellular mechanisms by which the most relevant viral, bacterial and parasitic infections influence the progression of fatty liver disease and steatohepatitis. We focus in particular on how infectious diseases, including coronavirus disease-19, hepatitis C, acquired immunodeficiency syndrome, peptic ulcer and periodontitis, exacerbate MAFLD. We specifically underscore the synergistic effects of these infections with other MAFLD-promoting factors.
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Affiliation(s)
- Joost Boeckmans
- Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
- Clinical Laboratory, Jessa Hospital, Stadsomvaart 11, 3500, Hasselt, Belgium.
| | - Matthias Rombaut
- Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
| | - Thomas Demuyser
- Department of Microbiology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
- Center for Neurosciences, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
| | - Baptist Declerck
- Department of Microbiology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
| | - Denis Piérard
- Department of Microbiology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
| | - Vera Rogiers
- Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
| | - Joery De Kock
- Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
| | - Luc Waumans
- Clinical Laboratory, Jessa Hospital, Stadsomvaart 11, 3500, Hasselt, Belgium
| | - Koen Magerman
- Clinical Laboratory, Jessa Hospital, Stadsomvaart 11, 3500, Hasselt, Belgium
- Department of Immunology and Infection, Hasselt University, Martelarenlaan 42, 3500, Hasselt, Belgium
| | - Reinoud Cartuyvels
- Clinical Laboratory, Jessa Hospital, Stadsomvaart 11, 3500, Hasselt, Belgium
| | - Jean-Luc Rummens
- Clinical Laboratory, Jessa Hospital, Stadsomvaart 11, 3500, Hasselt, Belgium
| | - Robim M Rodrigues
- Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
| | - Tamara Vanhaecke
- Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
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Sanabria-Cabrera J, Sanjuán-Jiménez R, Clavijo E, Medina-Cáliz I, González-Jiménez A, García-Cortés M, Ortega-Alonso A, Jiménez-Pérez M, González-Grande R, Stephens C, Robles-Díaz M, Lucena MI, Andrade RJ. Incidence and prevalence of acute hepatitis E virus infection in patients with suspected Drug-Induced Liver Injury in the Spanish DILI Registry. Liver Int 2021; 41:1523-1531. [PMID: 33107176 DOI: 10.1111/liv.14713] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 09/23/2020] [Accepted: 10/16/2020] [Indexed: 02/13/2023]
Abstract
BACKGROUND AND AIMS Drug-induced liver injury (DILI) presents with a wide phenotypic spectrum requiring an extensive differential diagnosis. Hepatitis E virus (HEV) is not systematically ruled out during acute hepatitis assessment in Spain. The aims of this study were to establish the role of HEV infection and its phenotypic presentation in patients initially suspected of DILI and to determine the anti-HEV seroprevalence rate. METHODS An analysis of 265 patients with suspected DILI and considered for enrolment in the Spanish DILI Registry and 108 controls with normal liver profiles was undertaken. Anti-HEV Immunoglobulin (Ig) G antibodies were analysed in serum from all subjects. In those with serum samples extracted within 6 months from liver damage onset (n = 144), HEV antigen (Ag) and anti-HEV IgM antibodies were tested in duplicate by ELISA. In addition, RT-PCR was performed externally in eight patients. RESULTS Out of 144 patients, 12 (8%) were positive for anti-HEV IgM, mean age was 61 years. Underlying hepatic diseases (OR = 23.4, P < .001) and AST peak >20 fold upper limit of normal (OR = 10.9, P = .002) were associated with the diagnosis of acute hepatitis E. The overall anti-HEV IgG seroprevalence rate was 35%, evenly distributed between patients with suspected DILI (34%), and controls (39%). CONCLUSIONS HEV seroprevalence and acute hepatitis E rates are relatively high in Spain. A search for active HEV infection is therefore advised in patients assessed for suspicion of DILI, particularly in patients with underlying liver diseases and high transaminase levels.
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Affiliation(s)
- Judith Sanabria-Cabrera
- UICEC IBIMA, Plataforma SCReN (Spanish Clinical Research Network), Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Universidad de Malaga, Málaga, Spain
- Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain
| | - Rocío Sanjuán-Jiménez
- UICEC IBIMA, Plataforma SCReN (Spanish Clinical Research Network), Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Universidad de Malaga, Málaga, Spain
- Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain
| | - Encarnación Clavijo
- Servicio de Microbiología, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain
| | - Inmaculada Medina-Cáliz
- Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain
| | - Andrés González-Jiménez
- Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain
| | - Miren García-Cortés
- Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain
- CIBERehd (Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas), Madrid, Spain
| | - Aida Ortega-Alonso
- Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain
| | - Miguel Jiménez-Pérez
- Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Regional de Málaga, Málaga, Spain
| | - Rocío González-Grande
- Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Regional de Málaga, Málaga, Spain
| | - Camilla Stephens
- Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain
- CIBERehd (Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas), Madrid, Spain
| | - Mercedes Robles-Díaz
- Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain
- CIBERehd (Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas), Madrid, Spain
| | - M Isabel Lucena
- UICEC IBIMA, Plataforma SCReN (Spanish Clinical Research Network), Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Universidad de Malaga, Málaga, Spain
- CIBERehd (Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas), Madrid, Spain
| | - Raúl J Andrade
- Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain
- CIBERehd (Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas), Madrid, Spain
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Katturajan R, Evan Prince S. A role of connexin 43 on the drug-induced liver, kidney, and gastrointestinal tract toxicity with associated signaling pathways. Life Sci 2021; 280:119629. [PMID: 34004253 DOI: 10.1016/j.lfs.2021.119629] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 05/04/2021] [Accepted: 05/11/2021] [Indexed: 12/25/2022]
Abstract
Drug-induced organ toxicity/injury, especially in the liver, kidney, and gastrointestinal tract, is a systematic disorder that causes oxidative stress formation and inflammation resulting in cell death and organ failure. Current therapies target reactive oxygen species (ROS) scavenging and inhibit inflammatory factors in organ injury to restore the functions and temporary relief. Organ cell function and tissue homeostasis are maintained through gap junction intercellular communication, regulating connexin hemichannels. Mis-regulation of such connexin, especially connexin (Cx) 43, affects a comprehensive process, including cell differentiation, inflammation, and cell death. Aim to describe knowledge about the importance of connexin role and insights therapeutic targeting. Cx43 misregulation has been implicated in recent decades in various diseases. Moreover, in recent years there is increasing evidence that Cx43 is involved in the toxicity process, including hepatic, renal, and gastrointestinal disorders. Cx43 has the potential to initiate the immune system to cause cell death, which has been activated in the acceleration of apoptosis, necroptosis, and autophagy signaling pathway. So far, therapies targeting Cx43 have been under inspection and are subjected to clinical trial phases. This review elucidates the role of Cx43 in drug-induced vital organ injury, and recent reports compromise its function in the major signaling pathways.
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Affiliation(s)
- Ramkumar Katturajan
- Department of Biomedical Sciences, School of Biosciences and Technology, VIT, Vellore, Tamil Nadu, India.
| | - Sabina Evan Prince
- Department of Biomedical Sciences, School of Biosciences and Technology, VIT, Vellore, Tamil Nadu, India.
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ACG Clinical Guideline: Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury. Am J Gastroenterol 2021; 116:878-898. [PMID: 33929376 DOI: 10.14309/ajg.0000000000001259] [Citation(s) in RCA: 192] [Impact Index Per Article: 48.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 01/25/2021] [Indexed: 12/11/2022]
Abstract
Idiosyncratic drug-induced liver injury (DILI) is common in gastroenterology and hepatology practices, and it can have multiple presentations, ranging from asymptomatic elevations in liver biochemistries to hepatocellular or cholestatic jaundice, liver failure, or chronic hepatitis. Antimicrobials, herbal and dietary supplements, and anticancer therapeutics (e.g., tyrosine kinase inhibitors or immune-checkpoint inhibitors) are the most common classes of agents to cause DILI in the Western world. DILI is a diagnosis of exclusion, and thus, careful assessment for other etiologies of liver disease should be undertaken before establishing a diagnosis of DILI. Model for end-stage liver disease score and comorbidity burden are important determinants of mortality in patients presenting with suspected DILI. DILI carries a mortality rate up to 10% when hepatocellular jaundice is present. Patients with DILI who develop progressive jaundice with or without coagulopathy should be referred to a tertiary care center for specialized care, including consideration for potential liver transplantation. The role of systemic corticosteroids is controversial, but they may be administered when a liver injury event cannot be distinguished between autoimmune hepatitis or DILI or when a DILI event presents with prominent autoimmune hepatitis features.
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Dinis-Oliveira RJ. Pharmacokinetics, toxicological and clinical aspects of ulipristal acetate: insights into the mechanisms implicated in the hepatic toxicity. Drug Metab Rev 2021; 53:375-383. [PMID: 33905271 DOI: 10.1080/03602532.2021.1917599] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Ulipristal acetate is a drug used as emergency contraceptive (30 mg) and for the treatment of moderate to severe symptoms of uterine myomas (5 mg). After commercialization, and although the exact number is unknown, serious cases implying ulipristal acetate 5 mg as a contributing factor of liver injury, some leading to transplantation, were reported. These cases prompted to a restrict use of the drug in January 2021 by the European Medicines Agency. This work aimed to fully review pharmacokinetic aspects, namely focusing in the ulipristal acetate metabolism and other hypothetical toxicological underlying mechanisms that may predispose to drug-induced liver injury (DILI). The high lipophilicity, the extensive hepatic metabolism, the long half-life of the drug and of its major active metabolite, the long-term course of treatment, and possibility due to the formation of epoxide reactive may be contributing factors. Scientific results also points evidence to consider monitorization of liver function during ulipristal acetate treatment.
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Affiliation(s)
- Ricardo Jorge Dinis-Oliveira
- IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), Advanced Polytechnic and University Cooperative (CESPU), CRL, Gandra, Portugal.,Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, Porto, Portugal.,UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
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Gao E, Hercun J, Heller T, Vilarinho S. Undiagnosed liver diseases. Transl Gastroenterol Hepatol 2021; 6:28. [PMID: 33824932 DOI: 10.21037/tgh.2020.04.04] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 03/19/2020] [Indexed: 02/06/2023] Open
Abstract
The landscape of chronic liver disease has drastically changed over the past 20 years, largely due to advances in antiviral therapy and the rise of metabolic syndrome and associated non-alcoholic fatty liver disease (NAFLD). Despite advances in the diagnosis and treatment of a variety of liver diseases, the burden of chronic liver disease is increasing worldwide. The first step to addressing any disease is accurate diagnosis. Here, we discuss liver diseases that remain undiagnosed, either because they are difficult to diagnose or due to hepatic manifestations of an unrecognized systemic disease. Additionally, their underlying etiology may remain unknown or they represent previously uncharacterized and therefore novel liver diseases. Our goal is to provide a framework for approaching undiagnosed liver diseases which elude standard hepatic diagnostic work-up and whose patterns of disease are often overlooked.
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Affiliation(s)
- Emily Gao
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA
| | - Julian Hercun
- Translational Hepatology Section, National Institute of Diabetes & Digestive & Kidney Diseases, National Institute of Health, Bethesda, MD, USA
| | - Theo Heller
- Translational Hepatology Section, National Institute of Diabetes & Digestive & Kidney Diseases, National Institute of Health, Bethesda, MD, USA
| | - Sílvia Vilarinho
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA.,Department of Pathology, Yale School of Medicine, New Haven, CT, USA
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Obeidat AE, Monti G, Sae-Ow W, Shinoda H, Lim H. Hepatitis E Virus Superinfection: an Underrecognized Trigger of Acute Hepatitis B Virus Flare. Cureus 2021; 13:e13809. [PMID: 33859880 PMCID: PMC8038892 DOI: 10.7759/cureus.13809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Hepatitis E virus (HEV) infection is a significant cause of acute hepatitis in endemic areas, such as parts of Asia, Africa, and Mexico, though HEV prevalence in the United States has been estimated between 6% and 20%. Chronic hepatitis B virus (HBV) infection affects about 1 per 1.4 million people in North America. Although well documented in Asia, HBV flare secondary to HEV superinfection is rarely reported in the United States. Here, we present a case of chronic undiagnosed HBV infection with acute flare secondary to HEV superinfection.
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Affiliation(s)
| | - Gabriel Monti
- School of Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, USA
| | - Wichit Sae-Ow
- Pathology, The Queen's Medical Center, Honolulu, USA
| | | | - Herbert Lim
- Gastroenterology and Hepatology, The Queen's Medical Center, Honolulu, USA
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Grama A, Pop TL. Etiology of acute liver failure in children. PEDIATRU.RO 2021; 3:22. [DOI: 10.26416/pedi.63.3.2021.5483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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The histologic presentation of hepatitis E reflects patients' immune status and pre-existing liver condition. Mod Pathol 2021; 34:233-248. [PMID: 32572157 PMCID: PMC7806507 DOI: 10.1038/s41379-020-0593-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 05/27/2020] [Accepted: 05/27/2020] [Indexed: 02/08/2023]
Abstract
Infection with the hepatitis E virus (HEV) is one of the main causes of acute hepatitis worldwide. Given that, the histopathology of hepatitis E is relatively poorly characterized, and it is unclear what exactly determines its remarkable variability. The aim of our study was a systematic analysis of hepatitis E histology, especially with regard to the clinical setting. Fifty-two liver samples (48 biopsies, 1 liver explant, 3 autopsy livers) from 41 patients with molecularly proven hepatitis E (28 HEV genotype (gt) 3, three gt 1, one gt 4 and 9 undetermined gt) were systematically evaluated for 33 histopathologic features. Following one approach, the biopsies were assigned to one of five generic histologic patterns. In another approach, they were subjected to hierarchical clustering. We found that 23/41 (56%) patients were immunocompromised, whereas 18 (44%) had no known immunosuppression. Five patients (12%) had pre-existing liver disease (LD). The histopathologic spectrum ranged from almost normal to acute, chronic, and steato-hepatitis to subtotal necrosis, and was thus distributed across all five generic patterns. Hierarchical clustering, however, identified three histopathologic clusters (C1-C3), which segregated along the immune status and pre-existing LD: C1 comprised mostly patients with pre-existing LD; histology mainly reflected the respective LD without pointing to the additional hepatitis E. C2 comprised mostly immunocompetent patients; histology mainly displayed florid hepatitis. C3 comprised mostly immunocompromised patients; histology mainly displayed smoldering hepatitis. Accordingly, C1-C3 differed markedly with respect to their clinical and histopathologic differential diagnoses. Hierarchical clustering suggests three groups with distinct histopathologies, indicating biologically different manifestations of hepatitis E. The association of histopathologic changes with the patient's immune status and pre-existing LD plausibly explains the diversity of hepatitis E histopathology, and suggests that these factors are the crucial underlying determinants. We expect our results to improve patient management by guiding the clinico-pathologic diagnosis of hepatitis E.
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Houron C, Danielou M, Mir O, Fromenty B, Perlemuter G, Voican CS. Multikinase inhibitor-induced liver injury in patients with cancer: A review for clinicians. Crit Rev Oncol Hematol 2020; 157:103127. [PMID: 33161366 DOI: 10.1016/j.critrevonc.2020.103127] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 09/29/2020] [Accepted: 10/05/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Multikinase inhibitors (MKI) are targeted molecular agents that have revolutionized cancer management. However, there is a paucity of data concerning MKI-related liver injury risk and clinical guidelines for the management of liver toxicity in patients receiving MKI for cancer are scarce. DESIGN We conducted a PubMed search of articles in English published from January 2000 to December 2018 related to hepatotoxicity of the 29 FDA-approved MKIs at doses used in clinical practice. The search terms were the international non-proprietary name of each agent cross-referenced with «hepatotoxicity», «hepatitis», «hepatic adverse event», or «liver failure», and «phase II clinical trial», «phase III clinical trial», or «case report». RESULTS Following this search, 140 relevant studies and 99 case reports were considered. Although asymptomatic elevation of aminotransferase levels has been frequently observed in MKI clinical trials, clinically significant hepatotoxicity is a rare event. In most cases, the interval between treatment initiation and the onset of liver injury is between one week and two months. Liver toxicity is often hepatocellular and less frequently mixed. Life-threatening MKI-induced hepatic injury has been described, involving fulminant liver failure or death. Starting from existing data, a description of MKI-related liver events, grading of hepatotoxicity risk, and recommendations for management are also given for various MKI molecules. CONCLUSION All MKIs can potentially cause liver injury, which is sometimes irreversible. As there is still no strategy available to prevent MKI-related hepatotoxicity, early detection remains crucial. The surveillance of liver function during treatment may help in the early detection of hepatotoxicity. Furthermore, the exclusion of potential causes of hepatic injury is essential to avoid unnecessary MKI withdrawal.
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Affiliation(s)
- Camille Houron
- Faculté de Médecine Paris-Saclay, Université Paris-Saclay, F-94276, Le Kremlin-Bicêtre, France; INSERM U996, DHU Hepatinov, Labex LERMIT, F-92140, Clamart, France
| | - Marie Danielou
- Faculté de Médecine Paris-Saclay, Université Paris-Saclay, F-94276, Le Kremlin-Bicêtre, France; Service d'Hépato-Gastroentérologie et Nutrition, Hôpital Antoine-Béclère, AP-HP, Université Paris-Saclay, F-92140, Clamart, France
| | - Olivier Mir
- Gustave Roussy Cancer Campus, Department of Ambulatory Care, F-94805, Villejuif, France
| | - Bernard Fromenty
- INSERM, INRAE, Univ Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), UMR_A 1341, UMR_S 1241, F-35000, Rennes, France
| | - Gabriel Perlemuter
- Faculté de Médecine Paris-Saclay, Université Paris-Saclay, F-94276, Le Kremlin-Bicêtre, France; INSERM U996, DHU Hepatinov, Labex LERMIT, F-92140, Clamart, France; Service d'Hépato-Gastroentérologie et Nutrition, Hôpital Antoine-Béclère, AP-HP, Université Paris-Saclay, F-92140, Clamart, France.
| | - Cosmin Sebastian Voican
- Faculté de Médecine Paris-Saclay, Université Paris-Saclay, F-94276, Le Kremlin-Bicêtre, France; INSERM U996, DHU Hepatinov, Labex LERMIT, F-92140, Clamart, France; Service d'Hépato-Gastroentérologie et Nutrition, Hôpital Antoine-Béclère, AP-HP, Université Paris-Saclay, F-92140, Clamart, France
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Fontana RJ, Engle RE, Gottfried M, Hammed B, Hanje J, Durkalski V, Kleiner DE, Nguyen H, Nishimura N, Lee WM, Farci P. Role of Hepatitis E Virus Infection in North American Patients With Severe Acute Liver Injury. Clin Transl Gastroenterol 2020; 11:e00273. [PMID: 33259165 PMCID: PMC7665257 DOI: 10.14309/ctg.0000000000000273] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 10/07/2020] [Indexed: 12/17/2022] Open
Abstract
INTRODUCTION The aim of this study was to determine the role of hepatitis E virus (HEV) infection in a large cohort of prospectively enrolled patients with severe acute liver injury (ALI). METHODS Serum samples from 594 consecutive adults enrolled between 2008 and 2018 in the US Acute Liver Failure Study Group ALI registry were tested for anti-HEV IgM and anti-HEV IgG levels. Those with detectable anti-HEV IgM underwent further testing for HEV RNA using real-time polymerase chain reaction. RESULTS The median age of patients was 38 years; 41% were men and 72% Caucasian. Etiologies of ALI included acetaminophen hepatotoxicity (50%), autoimmune hepatitis (8.9%), hepatitis B virus (8.9%), and idiosyncratic drug-induced liver injury (7.9%). Overall, 62 patients (10.4%) were negative for anti-HEV IgM but positive for IgG, whereas only 3 men (0.5%) were positive for both anti-HEV IgM and IgG. These 3 cases were initially diagnosed as having indeterminate, HEV, and hepatitis B virus-related ALI. One of these patients had detectable HEV RNA genotype 3, and another anti-HEV IgM+ patient had detectable HEV antigens by immunohistochemistry on liver biopsy. On multivariate modeling, older (odds ratio: 1.99) and non-Caucasian subjects (odds ratio: 2.92) were significantly more likely to have detectable anti-HEV IgG (P < 0.0001). DISCUSSION Acute HEV infection is an infrequent cause of ALI in hospitalized North American adults. The anti-HEV IgG+ patients were significantly older and more likely to be non-Caucasian. These data are consistent with other population-based studies that indicate exposure to HEV in the general US population is declining over time and might reflect a cohort effect.
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Affiliation(s)
- Robert J. Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Ronald E. Engle
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - Michelle Gottfried
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Bilal Hammed
- Department of Medicine, UCSF, San Francisco, California, USA
| | - James Hanje
- Department of Medicine, Ohio State University, Columbus, Ohio, USA
| | - Valerie Durkalski
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - David E. Kleiner
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Hanh Nguyen
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - Norihisa Nishimura
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - William M. Lee
- Department of Medicine, University of Texas Southwestern, Dallas, Texas, USA
| | - Patrizia Farci
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
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Aslan AT, Balaban HY. Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment. World J Gastroenterol 2020; 26:5543-5560. [PMID: 33071523 PMCID: PMC7545399 DOI: 10.3748/wjg.v26.i37.5543] [Citation(s) in RCA: 110] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 08/11/2020] [Accepted: 09/09/2020] [Indexed: 02/06/2023] Open
Abstract
The hepatitis E virus (HEV) is the fifth known form of viral hepatitis and was first recognized as the cause of an epidemic of unexplained acute hepatitis in the early 1980s. Globally, it is one of the most frequent causes of acute viral hepatitis. The majority of HEV infections are asymptomatic and lead to the spontaneous clearance of the virus. Among the eight different genotypes identified to date, HEV genotype 1 (HEV1), HEV2, HEV3, and HEV4 are the most frequent genotypes causing infections in humans. HEV1 and HEV2 are prevalent in developing regions and able to result in large-scale outbreaks originating from contaminated water supplies. They are also responsible for severe hepatitis in pregnant patients and infants. In contrast, HEV3 and HEV4 are zoonotic, and the transmission of these genotypes to humans occurs mainly through the fecal contamination of water and consumption of contaminated meat from infected animals. Their main reservoir is the pig, and they are mostly encountered in developed countries. The major risk groups for HEV infection and its ensuing adverse consequences are pregnant women, infants, older people, immunocompromised individuals, patients with underlying chronic liver diseases, and workers that come into close contact with HEV-infected animals. In the clinical perspective, HEV infections have diverse clinical manifestations including acute and self-limiting hepatitis, acute-on-chronic liver disease, chronic hepatitis, cirrhosis, and liver failure. Although HEV mainly results in acute self-limiting infection, chronic HEV infection may occur among immunocompromised patients (e.g., solid-organ transplant recipients). Additionally, HEV-associated extrahepatic manifestations involving various organs have been reported in the last decade, although the causal link for many of them still needs to be proven. Ribavirin and interferon-alpha are the most widely used agents for the treatment of HEV infections with a certain level of success. However, ribavirin is contraindicated in pregnant patients, and interferon-alpha cannot be used in most transplant recipients. Therefore, there is an urgent need for novel antiviral compounds that are safe and effective particularly for patients having contraindications for ribavirin or interferon-alpha and infected by the ribavirin-resistant HEV. In this review article, a literature search using PubMed and MEDLINE databases was performed, up to March 2020. Only the articles published in English were reviewed.
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Affiliation(s)
| | - Hatice Yasemin Balaban
- Department of Gastroenterology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey
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Abstract
Kratom (Mitragyna speciosa) leaves contain the mu opioid partial agonists mitragynine and 7-hydroxymitragynine. The US Drug Enforcement Agency considers it a 'drug of concern', and the US FDA is reviewing kratom, but there is a paucity of information regarding health effects. Liver injury is often cited as a potential health consequence, however the same few case reports are repeatedly referenced, without a broader context. Furthermore, reports have largely lacked standardized causality assessment methods. The objective is to evaluate causality in kratom liver injury, through a comprehensive scoping review of human cases, and by reviewing epidemiologic, animal, and mechanistic reports that relate to kratom liver injury. Hepatotoxicity causality was systematically examined using the Roussel Uclaf Causality Assessment Method (RUCAM) for case reports. Biopsy findings, potential pathophysiologic mechanisms, and management options are discussed. This review identified 26 case reports and abstracts, in addition to 7 cases reported from the Drug-Induced Liver Injury Network, 25 in FDA databases, and 27 in internet user forums. Latency periods to symptom onset had a median of 20.6 days and mean of 21 days (range 2-49). Common presenting signs and symptoms were abdominal discomfort, jaundice, pruritis, and dark urine. Histologic findings were predominantly cholestatic, although, biochemically, the condition was heterogenous or mixed; the median R ratio was 3.4 and the mean was 4.6 (range 0.24-10.4). Kratom likely causes liver injury based on the totality of low-quality human evidence, and, in the context of epidemiologic, animal, and mechanistic studies. It remains unclear which subgroups of users are at heightened risk.
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Affiliation(s)
- Jonathan Schimmel
- Department of Emergency Medicine, Division of Medical Toxicology, Mount Sinai Hospital Icahn School of Medicine, New York, NY, USA.
| | - Richard C Dart
- Rocky Mountain Poison and Drug Safety, Denver Health and Hospital Authority, Denver, CO, USA
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Mendoza-Lopez C, Lopez-Lopez P, Atienza-Ayala S, Rivero-Juarez A, Benito R. Parsonage-Turner syndrome associated with hepatitis E infection in immunocompetent patients. Virus Res 2020; 290:198165. [PMID: 33007343 DOI: 10.1016/j.virusres.2020.198165] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 09/03/2020] [Accepted: 09/08/2020] [Indexed: 02/08/2023]
Abstract
Introduction The hepatitis E virus (HEV) is the leading cause of acute hepatitis around the world. In recent years, knowledge has increased concerning extrahepatic manifestations caused by HEV, including neurological manifestations such as Parsonage-Turner syndrome (PTS). PTS is characterized by severe shoulder or arm pain and patchy paresis with muscle weakness. The aim of the present study was to assess the association between HEV and PTS. Materials and Methods We reported two cases of PTS associated with HEV, which were diagnosed in a short period of time in the same village. PTS was diagnosed by physical examination and electrophysiological studies, and serology testing for IgM, low-avidity IgG, and RNA of HEV established the diagnosis of acute HEV infection. Results A 44-year-old man who presented cervicobrachial pain accompanied by paresthesia, dyspnea, and isolated derangement of liver enzymes and 57-year-old women with cervical pain radiated to upper limbs, paresthesia, and liver cytolysis, although, this patient was initially diagnosed as having drug-induced hepatitis. Finally, the diagnosis was Parsonage- Turner syndrome associated with hepatitis e virus. In both patients, symptoms were bilateral and they required hospital admission. Both consumed vegetables are grown in a local patch and the phylogenetic analysis showed genotype 3f. Then, we reviewed the literature on PTS and HEV and we found 62 previously described cases that were more likely to be men (86.20 %) with more frequent bilateral symptoms (85.71 %). Genotype 3 is the most commonly associated. Three of those cases were diagnosed in Spain. Conclusions According to our findings, HEV should be considered in patients with neuralgic amyotrophy, including those with the absence of liver cytolysis.
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Affiliation(s)
- Claudia Mendoza-Lopez
- Microbiology Department, University Clinical Lozano Blesa Hospital, Zaragoza, Spain.
| | - Pedro Lopez-Lopez
- Infectious Diseases Unit, Clinical Virology and Zoonoses Unit, Maimonides Institute for Biomedical Research, Reina Sofia Hospital, University of Cordoba, Cordoba, Spain
| | - Saida Atienza-Ayala
- Neurology Department, University Clinical Lozano Blesa Hospital, Zaragoza, Spain
| | - Antonio Rivero-Juarez
- Infectious Diseases Unit, Clinical Virology and Zoonoses Unit, Maimonides Institute for Biomedical Research, Reina Sofia Hospital, University of Cordoba, Cordoba, Spain
| | - Rafael Benito
- Microbiology Department, University Clinical Lozano Blesa Hospital, Zaragoza, Spain
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Bourhia M, Ullah R, S Alqahtani A, Ibenmoussa S. Evidence of drug-induced hepatotoxicity in the Maghrebian population. Drug Chem Toxicol 2020; 45:985-989. [PMID: 32715778 DOI: 10.1080/01480545.2020.1797088] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Drug-induced hepatotoxicity is one of the most challenging hepatic diseases faced nowadays due to a large number of drugs currently used in clinical practice, the enormous dietary supplements which are potentially hepatotoxic, as well as the ability to appear with different clinical symptoms and the absence of specific markers. The current research survey was conducted to investigate drug-induced hepatotoxicity and demographic characteristics of patients with liver damage in the general Maghrebian population between 1992 and 2018. To achieve this goal a questionnaire was adopted to report details on the undesirable effects of drugs and demographic characteristics of affected patients. The results obtained in the current survey showed that 1001 in 25 093 cases of drug-induced toxicity were registered with drug-induced liver damage between 1992 and 2018. Regarding demographic characteristics of affected patients, the most affected age group was 18 to 44-years-old with a percentage of 45.70% followed by the age group 45 to 64-year-old with a percentage of 27.20%. Females were the most frequently affected by the hepatic side effects of drugs vs. males. Paracetamol, isoniazid, rifampicin, and pyrazinamide were the main responsible drugs for liver damage in the study population. Alteration of biological parameters and subclinical phenomena were used as clinical manifestations of liver damage in the study population. The outcome of the present study suggests paying more attention to drugs used for medication and the involvement of rigorous clinical monitoring to prevent or to minimize the side effects of drugs.
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Affiliation(s)
- Mohammed Bourhia
- Faculty of Medicine and Pharmacy, Laboratory of Chemistry-Biochemistry, Environment, Nutrition, and Health, Hassan II University, Casablanca, Morocco
| | - Riaz Ullah
- Department of Pharmacognosy (Medicinal Aromatic and Poisonous Plants Research Center), College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Ali S Alqahtani
- Department of Pharmacognosy (Medicinal Aromatic and Poisonous Plants Research Center), College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Samir Ibenmoussa
- Faculty of Medicine and Pharmacy, Laboratory of Chemistry-Biochemistry, Environment, Nutrition, and Health, Hassan II University, Casablanca, Morocco
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Wu G, Win S, Than TA, Chen P, Kaplowitz N. Gut Microbiota and Liver Injury (I)-Acute Liver Injury. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1238:23-37. [PMID: 32323178 DOI: 10.1007/978-981-15-2385-4_3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Over the last few decades, intestinal microbial communities have been considered to play a vital role in host liver health. Acute liver injury (ALI) is the manifestation of sudden hepatic injury and arises from a variety of causes. The studies of dysbiosis in gut microbiota provide new insight into the pathogenesis of ALI. However, the relationship of gut microbiota and ALI is not well understood, and the contribution of gut microbiota to ALI has not been well characterized. In this chapter, we integrate several major pathogenic factors in ALI with the role of gut microbiota to stress the significance of gut microbiota in prevention and treatment of ALI.
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Affiliation(s)
- Guangyan Wu
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, N.No 1838 Guangzhou Ave., Guangzhou, 510515, China
| | - Sanda Win
- USC Research Center for Liver Disease, Department of Medicine, Keck School of Medicine of USC, Los Angeles, CA, 90089, USA
| | - Tin A Than
- USC Research Center for Liver Disease, Department of Medicine, Keck School of Medicine of USC, Los Angeles, CA, 90089, USA
| | - Peng Chen
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, N.No 1838 Guangzhou Ave., Guangzhou, 510515, China
| | - Neil Kaplowitz
- USC Research Center for Liver Disease, Department of Medicine, Keck School of Medicine of USC, Los Angeles, CA, 90089, USA.
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Whitsett M, Feldman DM, Jacobson I. Hepatitis E Virus Infection in the United States: Current Understanding of the Prevalence and Significance in the Liver Transplant Patient Population and Proposed Diagnostic and Treatment Strategies. Liver Transpl 2020; 26:709-717. [PMID: 32061053 DOI: 10.1002/lt.25732] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 01/28/2020] [Indexed: 02/07/2023]
Abstract
Hepatitis E virus (HEV), of the family Herpesviridae, is a virus that infects nearly 20 million people per year throughout the world. HEV is most commonly transmitted via the fecal-oral route and has long been described as a virus that afflicts only those in resource-poor countries. However, HEV has been detected in numerous animal carriers, various food sources, and even in human blood products in resource-rich regions of the world. HEV is of importance in the transplant patient population because of its ability to cause chronic viral infection in these patients can lead to graft loss and cirrhosis. In this review, we discuss the current knowledge of HEV as it pertains to the liver transplant patient population and discuss diagnosis and treatment of this infection.
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Affiliation(s)
- Maureen Whitsett
- Department of Gastroenterology and Hepatology, NYU Langone Health, NYU Grossman School of Medicine, New York University, New York, NY
| | - David M Feldman
- Department of Gastroenterology and Hepatology, NYU Langone Health, NYU Grossman School of Medicine, New York University, New York, NY
| | - Ira Jacobson
- Department of Gastroenterology and Hepatology, NYU Langone Health, NYU Grossman School of Medicine, New York University, New York, NY
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Mendizabal M, Haddad L, Marciano S, Ganem FO, Paz S, Gruz F, Ridruejo E, Lurbet MF, Fernandez N, Descalzi V, Anders M, Gadano A, Martínez A, Silva YM. Hepatitis E infection is an infrequent cause of acute hepatitis in the metropolitan area of Buenos Aires. J Clin Virol 2020; 126:104309. [PMID: 32155452 DOI: 10.1016/j.jcv.2020.104309] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 03/01/2020] [Accepted: 03/05/2020] [Indexed: 12/17/2022]
Abstract
UNLABELLED Background Argentina is considered a region of low seroprevalence of hepatitis E virus (HEV), however; no studies have evaluated its burden among acute hepatitis cases. OBJECTIVES We aimed to estimate the proportion of acute HEV and outcome in a cohort of patients with acute hepatitis from 6 liver units in the Metropolitan area of Buenos Aires (MABA). STUDY DESIGN We performed a prospective cohort study including patients ≥18 years with acute hepatitis (increase in transaminases x 5 ULN) fromJuly 2016 to May 2018. Severe hepatitis was defined as acute hepatitis + INR> 1.5 and acute liver failure as severe hepatitis + encephalopathy. In patients in whom other etiologies were excluded, HEV tests were performed: anti-HEV IgM/G and HEV-RNA in serum and feces. RESULTS Overall, 268 patients with acute hepatitis were included in the study. The most frequent etiologies of acute hepatitis were hepatitis B (67patients, 25 %), hepatotoxicity (65, 24 %) and autoimmune hepatitis (26, 10 %). Acute HEV infection was confirmed in 8 (2.98 %; 95 %CI 1.25-5.63) patients who tested positive for anti-HEV IgM. A total of 63 (23.5 %) patients were hospitalized and 9 (3.3 %) patients died. Overall, 48 (18 %) patients developed severe hepatitis, 6 (2.2 %) have acute liver failure, 6 (1.9 %) underwent liver transplantation and 9 (3.4 %) patients died. CONCLUSIONS the proportion of acute HEV in MABA was low during the period studied. We believe our findings will aid physicians prioritize other etiologies of acute hepatitis over HEV in order to optimize diagnostic resources and offer better care to their patients.
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Affiliation(s)
- Manuel Mendizabal
- Unidad de Hígado y Trasplante Hepático, Hospital Universitario Austral, Pilar, Argentina; Latin American Liver Research, Educational and Awareness Network (LALREAN).
| | - Leila Haddad
- Sección Hepatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Sebastián Marciano
- Sección Hepatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Departamento de Investigación, Hospital Italiano de Buenos Aires, Argentina
| | | | - Silvina Paz
- Unidad de Hígado, Hospital Británico, Buenos Aires, Argentina
| | - Fernando Gruz
- Hospital Italiano de La Plata, Buenos Aires, Argentina
| | - Ezequiel Ridruejo
- Unidad de Hígado y Trasplante Hepático, Hospital Universitario Austral, Pilar, Argentina; Latin American Liver Research, Educational and Awareness Network (LALREAN); Sección Hepatología, Centro de Educación Médica e Investigaciones Clínicas "CEMIC", Buenos Aires, Argentina
| | - María Fernanda Lurbet
- Sección Hepatología, Centro de Educación Médica e Investigaciones Clínicas "CEMIC", Buenos Aires, Argentina
| | - Nora Fernandez
- Latin American Liver Research, Educational and Awareness Network (LALREAN); Unidad de Hígado, Hospital Británico, Buenos Aires, Argentina
| | - Valeria Descalzi
- Latin American Liver Research, Educational and Awareness Network (LALREAN); Unidad de Hígado y Trasplante Hepático, Fundación Favaloro, Buenos Aires, Argentina
| | - Margarita Anders
- Latin American Liver Research, Educational and Awareness Network (LALREAN); Unidad de Hígado y Trasplante Hepático, Hospital Alemán, Buenos Aires, Argentina
| | - Adrián Gadano
- Sección Hepatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Departamento de Investigación, Hospital Italiano de Buenos Aires, Argentina
| | - Alfredo Martínez
- Laboratorio de Virología, Centro de Educación Médica e Investigaciones Clínicas "CEMIC", Buenos Aires, Argentina
| | - Y Marcelo Silva
- Unidad de Hígado y Trasplante Hepático, Hospital Universitario Austral, Pilar, Argentina; Latin American Liver Research, Educational and Awareness Network (LALREAN)
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Sooryanarain H, Meng XJ. Swine hepatitis E virus: Cross-species infection, pork safety and chronic infection. Virus Res 2020; 284:197985. [PMID: 32333941 DOI: 10.1016/j.virusres.2020.197985] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 04/11/2020] [Accepted: 04/17/2020] [Indexed: 12/12/2022]
Abstract
Swine hepatitis E virus (swine HEV) belongs to the species Orthohepevirus A within the genus Orthohepevirus in the family Hepeviridae. Four different genotypes of swine HEV within the species Orthohepevirus A have been identified so far from domesticated and wild swine population: genotypes 3 (HEV-3) and 4 (HEV-4) swine HEVs are zoonotic and infect humans, whereas HEV-5 and HEV-6 are only identified from swine. As a zoonotic agent, swine HEV is an emerging public health concern in many industrialized countries. Pigs are natural reservoir for HEV, consumption of raw or undercooked pork is an important route of foodborne HEV transmission. Occupational risks such as direct contact with infected pigs also increase the risk of HEV transmission in humans. Cross-species infection of HEV-3 and HEV-4 have been documented under experimental and natural conditions. Both swine HEV-3 and swine HEV-4 infect non-human primates, the surrogates of man. Swine HEV, predominantly HEV-3, can establish chronic infection in immunocompromised patients especially in solid organ transplant recipients. The zoonotic HEV-3, and to lesser extent HEV-4, have also been shown to cause neurological diseases and kidney injury. In this review, we focus on the epidemiology of swine HEV, host and viral determinants influencing cross-species HEV infection, zoonotic infection and its associated pork safety concern, as well as swine HEV-associated chronic infection and neurological diseases.
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Affiliation(s)
- Harini Sooryanarain
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Xiang-Jin Meng
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
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Larrue H, Abravanel F, Péron JM. Hepatitis E, what's the real issue? Liver Int 2020; 40 Suppl 1:43-47. [PMID: 32077607 DOI: 10.1111/liv.14351] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Accepted: 12/26/2019] [Indexed: 12/25/2022]
Abstract
Hepatitis E Virus (HEV) infection is a worldwide disease and the primary cause of acute viral hepatitis in the world with an estimated 20 million cases every year and 70 000 deaths. Hepatitis E is a waterborne infection in the developing countries. In these countries, HEV genotypes 1 and 2 cause large outbreaks and affect young subjects, resulting in significant mortality in pregnant women and patients with cirrhosis. In the developed countries, HEV genotypes 3 and 4 are responsible for autochthonous, sporadic hepatitis and transmission is zoonotic. Parenteral transmission by the transfusion of blood products has been identified as a potential new mode of transmission. The prevalence of positive HEV viraemia in blood donors in Europe ranges from 1/600 to 1/2500 in highly endemic European countries. HEV can cause neurological disorders and chronic infections in immunocompromised patients. The progression of acute hepatitis E is usually asymptomatic and resolves spontaneously. Diagnostic tools include anti-HEV IgM antibodies in serum and/or viral RNA detection in the blood or the stools by PCR. Ribavirin is used to treat chronic infection. A vaccine has been developed in China.
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Affiliation(s)
- Hélène Larrue
- Service d'hépatologie Hôpital Rangueil CHU Toulouse, Université Paul Sabatier III, Toulouse, France
| | - Florence Abravanel
- Laboratoire de Virologie Hôpital Purpan CHU Toulouse, Université Paul Sabatier III, Toulouse, France
| | - Jean-Marie Péron
- Service d'hépatologie Hôpital Rangueil CHU Toulouse, Université Paul Sabatier III, Toulouse, France
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Andrade RJ, Robles-Díaz M. Diagnostic and prognostic assessment of suspected drug-induced liver injury in clinical practice. Liver Int 2020; 40:6-17. [PMID: 31578817 DOI: 10.1111/liv.14271] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2019] [Revised: 09/17/2019] [Accepted: 09/19/2019] [Indexed: 02/13/2023]
Abstract
Idiosyncratic drug-induced liver injury (DILI) is a challenging liver disorder because it can present with a range of phenotypes, mimicking almost every other hepatic disease, and lacks specific biomarkers for its diagnosis. Hence, a confident DILI diagnosis is seldom possible as it relies on the precise establishment of a temporal sequence between the exposure to a given prescription drug or sometimes hidden herbal product/over the counter medication as well as the exclusion of other aetiologies of liver disease. However, an accurate diagnosis is of most importance, as prompt withdrawal of the causative agent is essential in DILI management. Indeed, DILI can be severe and even fatal or in a fraction of cases evolve to chronic damage, but specific biomarkers for predicting mortality/liver transplantation or a chronic outcome in the very early phases of DILI are not yet available. In this article, we discuss the best diagnostic and prognostic approach of a DILI suspicion by judiciously choosing and interpreting the standard tests currently used in clinical practice.
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Affiliation(s)
- Raúl J Andrade
- Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Universidad de Málaga, Malaga, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Mercedes Robles-Díaz
- Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Universidad de Málaga, Malaga, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
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