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Tiwari P, Singh N, Sharma B. Long Term Treatment of Corticostreroids May Cause Hepatotoxicity and Oxidative Damage: A Case Controlled Study. Indian J Clin Biochem 2023; 39:1-9. [PMID: 37360645 PMCID: PMC10066027 DOI: 10.1007/s12291-023-01127-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 02/23/2023] [Indexed: 04/05/2023]
Abstract
Arthritis is a clinical condition, which mainly affects the structure and function joints. During this condition the joints gets swelled and stiffed resulting into development of pain and morbidity. Corticosteroids are frequently prescribed to manage various clinical conditions including the chronic inflammatory diseases such as arthritis. The steroidal drug also causes certain adverse effects depending on the dose, the route of administration and duration of treatment. However, a systematic investigation on the biochemical consequences of steroids as a therapeutic has not been carried out. In the present study we analyzed certain parameters associated to oxidative stress, liver function and energy metabolism has been done in the blood plasma of the arthritis patients who were using steroidal drugs (methylprednisolone and deflazacort) up to 168 days for the treatment of the disease. The results indicated increase in level of MDA and decrease in the activities of SOD, CAT and LDH. The activities of AST and ALT were found to be significantly enhanced over the increase in the treatment period. These results suggested that corticosteroids may induce lipid peroxidation, oxidative stress and liver toxicity in the arthritis patients in the dose and duration dependent manner. The use of antioxidants as supplements to the anti-arthritis agents could play a role in suppressing the oxidative stress mediated adverse effects. However, extensive research is required to explore for safer medication devoid of steroids to cure arthritis. Graphical Abstract
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Affiliation(s)
- Priyanka Tiwari
- Department of Biochemistry, Faculty of Science, University of Allahabad, Allahabad, 211002 India
| | - Nitika Singh
- Department of Biochemistry, Faculty of Science, University of Allahabad, Allahabad, 211002 India
| | - Bechan Sharma
- Department of Biochemistry, Faculty of Science, University of Allahabad, Allahabad, 211002 India
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Chen Y, Shi C, Zhan H, Yang B, Liu J, Rong P, Luo Y, Yang J. Drug-induced liver injury in COVID-19 patients during hospitalization. Medicine (Baltimore) 2023; 102:e33294. [PMID: 36930097 PMCID: PMC10018522 DOI: 10.1097/md.0000000000033294] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 02/24/2023] [Indexed: 03/18/2023] Open
Abstract
Since coronavirus disease 2019 (COVID-19) outbreaks in December 2019 in Wuhan, almost no studies have systematically described drug-induced liver injury (DILI) in COVID-19 patients. This study aimed to assess the characteristics of liver test abnormality or liver injury in patients with COVID-19, and further to explore DILI in COVID-19 patients during hospitalization. It was a single-center retrospective analysis of confirmed severe acute respiratory syndrome coronavirus 2 infected patients in the hospital from January 2020 to March 2020. Univariate and multivariate logistic regression analysis were used to assess the risk factors associated with liver test abnormality or liver injury. At admission, 148 (48.8%, 148/303) patients had abnormal liver test results and 7 (2.4%, 7/303) had liver injury, while 195 (64.4%, 195/303) had abnormal liver test results and 17 (5.6%, 17/303) had liver injury during hospitalization. After excluding these patients with liver disease and liver function abnormalities or liver injury at admission, 15 (11.1%, 15/135) patients developed DILI during hospitalization. Further regression analysis indicated that methylprednisolone (odds ratio = 4.177, 95% confidence interval [1.106-15.771], P = .035), but not Chinese herbal medicine or other used drug, was associated with DILI in patients during hospitalization. Abnormal liver function results were in more than half of patients with COVID-19, and the incidence of DILI in COVID-19 patients was 11.1% during hospitalization. Liver test abnormality or liver injury in patients might be directly caused by the viral infection at admission, but the detrimental effects on liver injury mainly related to certain medications used during hospitalization, particularly methylprednisolone. Severe COVID-19 could increase the occurrence of liver injury (P = .007) during hospitalization, but not a risk factor of liver injury. However, Chinese herbal medicine was a protective factor for liver injury.
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Affiliation(s)
- Ying Chen
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - Cai Shi
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - Haiyan Zhan
- Department of Pharmacy, Wuhan Jinyintan Hospital, Wuhan, China
| | - Boning Yang
- Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Jun Liu
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - Peipei Rong
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yi Luo
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jian Yang
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
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Ciciriello AJ, Surnar B, Medy GD, Su X, Dhar S, Dumont CM. Biomaterial-targeted precision nanoparticle delivery to the injured spinal cord. Acta Biomater 2022; 152:532-545. [PMID: 36087868 PMCID: PMC10551882 DOI: 10.1016/j.actbio.2022.08.077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 07/29/2022] [Accepted: 08/31/2022] [Indexed: 11/01/2022]
Abstract
Drug delivery requires precision in timing, location, and dosage to achieve therapeutic benefits. Challenges in addressing all three of these critical criteria result in poor temporal dexterity, widespread accumulation and off-target effects, and high doses with the potential for toxicity. To address these challenges, we have developed the BiomatErial Accumulating Carriers for On-demand Nanotherapy (BEACON) platform that utilizes an implantable biomaterial to serve as a target for systemically delivered nanoparticles (NPs). With the BEACON system, administered NPs are conjugated with a ligand that has high affinity for a receptor in the implanted biomaterial. To test BEACON, an in vivo spinal cord injury (SCI) model was used as it provides an injury model where the three identified criteria can be tested as it is a dynamic and complicated injury model with no currently approved therapies. Through our work, we have demonstrated temporal dexterity in NP administration by injecting 6 days post-SCI, decreased off-target accumulation with a significant drop in liver accumulation, and retention of our NPs in the target biomaterial. The BEACON system can be applied broadly, beyond the nervous system, to improve systemically delivered NP accumulation at an implanted biomaterial target. STATEMENT OF SIGNIFICANCE: Targeted drug delivery approaches have the potential to improve therapeutic regimens for patients on a case-by-case basis. Improved localization of a therapeutic to site of interest can result in increased efficacy and limit the need for repeat dosing. Unfortunately, targeted strategies can fall short when receptors on cells or tissues are too widespread or change over the course of disease or injury progression. The BEACON system developed herein eliminates the need to target a cell or tissue receptor by targeting an implantable biomaterial with location-controllable accumulation and sustained presentation over time. The targeting paradigm presented by BEACON is widely applicable throughout tissue engineering and regenerative medicine without the need to retool for each new application.
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Affiliation(s)
- Andrew J Ciciriello
- Department of Biomedical Engineering, University of Miami, 1251 Memorial Drive, Coral Gables, FL 33146, United States; Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute at the University of Miami (BioNIUM), University of Miami, 1951 NW 7th Avenue, Miami, Florida 33136, United States
| | - Bapurao Surnar
- Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute at the University of Miami (BioNIUM), University of Miami, 1951 NW 7th Avenue, Miami, Florida 33136, United States; Department of Biochemistry & Molecular Biology, University of Miami, 1011 NW 15th Street, Miami, Florida 33136, United States
| | - Giovanni D Medy
- Department of Biomedical Engineering, University of Miami, 1251 Memorial Drive, Coral Gables, FL 33146, United States
| | - Xiaoyu Su
- Department of Biomedical Engineering, University of Miami, 1251 Memorial Drive, Coral Gables, FL 33146, United States
| | - Shanta Dhar
- Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute at the University of Miami (BioNIUM), University of Miami, 1951 NW 7th Avenue, Miami, Florida 33136, United States; Department of Biochemistry & Molecular Biology, University of Miami, 1011 NW 15th Street, Miami, Florida 33136, United States; Sylvester Comprehensive Cancer Center, University of Miami, 1475 NW 12th Avenue, Miami, Florida 33136, United States
| | - Courtney M Dumont
- Department of Biomedical Engineering, University of Miami, 1251 Memorial Drive, Coral Gables, FL 33146, United States; Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute at the University of Miami (BioNIUM), University of Miami, 1951 NW 7th Avenue, Miami, Florida 33136, United States; Department of Biochemistry & Molecular Biology, University of Miami, 1011 NW 15th Street, Miami, Florida 33136, United States.
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Kim SJ, Ko WK, Han GH, Lee D, Lee Y, Sheen SH, Hong JB, Sohn S. Chirality-Dependent Anti-Inflammatory Effect of Glutathione after Spinal Cord Injury in an Animal Model. Pharmaceuticals (Basel) 2021; 14:ph14080792. [PMID: 34451889 PMCID: PMC8398565 DOI: 10.3390/ph14080792] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 08/09/2021] [Accepted: 08/10/2021] [Indexed: 12/18/2022] Open
Abstract
Neuroinflammation forms a glial scar following a spinal cord injury (SCI). The injured axon cannot regenerate across the scar, suggesting permanent paraplegia. Molecular chirality can show an entirely different bio-function by means of chiral-specific interaction. In this study, we report that d-chiral glutathione (D-GSH) suppresses the inflammatory response after SCI and leads to axon regeneration of the injured spinal cord to a greater extent than l-chiral glutathione (L-GSH). After SCI, axon regrowth in D-GSH-treated rats was significantly increased compared with that in L-GSH-treated rats (*** p < 0.001). Secondary damage and motor function were significantly improved in D-GSH-treated rats compared with those outcomes in L-GSH-treated rats (** p < 0.01). Moreover, D-GSH significantly decreased pro-inflammatory cytokines and glial fibrillary acidic protein (GFAP) via inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway compared with L-GSH (*** p < 0.001). In primary cultured macrophages, we found that D-GSH undergoes more intracellular interaction with activated macrophages than L-GSH (*** p < 0.001). These findings reveal a potential new regenerative function of chiral GSH in SCI and suggest that chiral GSH has therapeutic potential as a treatment of other diseases.
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Affiliation(s)
- Seong-Jun Kim
- Department of Biomedical Science, CHA University, Seongnam-si 13493, Korea; (S.-J.K.); (W.-K.K.); (G.-H.H.); (D.L.)
| | - Wan-Kyu Ko
- Department of Biomedical Science, CHA University, Seongnam-si 13493, Korea; (S.-J.K.); (W.-K.K.); (G.-H.H.); (D.L.)
| | - Gong-Ho Han
- Department of Biomedical Science, CHA University, Seongnam-si 13493, Korea; (S.-J.K.); (W.-K.K.); (G.-H.H.); (D.L.)
| | - Daye Lee
- Department of Biomedical Science, CHA University, Seongnam-si 13493, Korea; (S.-J.K.); (W.-K.K.); (G.-H.H.); (D.L.)
| | - Yuhan Lee
- Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA;
| | - Seung-Hun Sheen
- Department of Neurosurgery, CHA Bundang Medical Center, Seongnam-si 13496, Korea;
| | - Je-Beom Hong
- Department of Neurosurgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Korea;
| | - Seil Sohn
- Department of Neurosurgery, CHA Bundang Medical Center, Seongnam-si 13496, Korea;
- Correspondence: ; Tel.: +82-31-881-7966
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Cottin J, Pierre S, Pizzoglio V, Simon C, Durrieu G, Bleyzac N, Gouraud A, Dumortier J. Methylprednisolone-related liver injury: A descriptive study using the French pharmacovigilance database. Clin Res Hepatol Gastroenterol 2020; 44:662-673. [PMID: 31948782 DOI: 10.1016/j.clinre.2019.12.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 12/03/2019] [Accepted: 12/18/2019] [Indexed: 02/04/2023]
Abstract
PURPOSE Hepatotoxicity associated with methylprednisolone (MP) is rarely reported in the literature. The aim of the present study was to review the characteristics of acute liver injury associated with intravenous (IV) or oral MP registered in the French pharmacovigilance database (FPD). METHODS All cases with MP coded as suspected, concomitant, or interacting drug associated with liver injury as the adverse effect reported up to May 2016 were extracted from the FPD. Cases were identified using the "Drug related hepatic disorders" Standard Medical Query. RESULTS A total of 97 cases of liver injury associated with MP were analysed; 58.8% were women and the median age was 46 years (range: 1-91). MP was used for an autoimmune disease in 47.6% of cases including 26 cases of multiple sclerosis, and was IV in 79.4% of cases. Nearly three-quarters of patients (73,2%) had a hepatocellular type of injury, the severity of which was mainly mild (45%) or moderate (31%). Most patients (92%) spontaneously and fully recovered within a mean 38.4 days. A rechallenge using the IV route was performed in 13 patients and for 10 (76.9%) this was positive (the initial type of injury was hepatocellular for all these cases). Regarding IV route of administration (n=77), MP was coded as the only suspected drug in 22% of cases. DISCUSSION The results suggest that IV MP causality should be considered in case of acute liver injury while data for oral MP is insufficient; systematic liver monitoring for high-dose IV MP may be recommended.
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Affiliation(s)
- Judith Cottin
- Service Hospitalo-Universitaire de Pharmacotoxicologie, Centre de Pharmacovigilance, Hospices Civils de Lyon, CHU-Lyon, 69003 Lyon, France.
| | - Sabrina Pierre
- Service Hospitalo-Universitaire de Pharmacotoxicologie, Centre de Pharmacovigilance, Hospices Civils de Lyon, CHU-Lyon, 69003 Lyon, France
| | - Véronique Pizzoglio
- Service Hospitalo-Universitaire de Pharmacotoxicologie, Centre de Pharmacovigilance, Hospices Civils de Lyon, CHU-Lyon, 69003 Lyon, France
| | - Corinne Simon
- Service de Pharmacosurveillance, Centre Régional de Pharmacovigilance, CHRU Tours, 37044 Tours, France
| | - Geneviève Durrieu
- Service de Pharmacologie Médicale et Clinique, Centre Régional de PharmacoVigilance, de Pharmaco-épidémiologie et d'Informations sur le Médicament, INSERM U 1027, Faculté de Médecine, Centre Hospitalier Universitaire, 31000 Toulouse, France
| | - Nathalie Bleyzac
- Service Hospitalo-Universitaire de Pharmacotoxicologie, Centre de Pharmacovigilance, Hospices Civils de Lyon, CHU-Lyon, 69003 Lyon, France
| | - Aurore Gouraud
- Service Hospitalo-Universitaire de Pharmacotoxicologie, Centre de Pharmacovigilance, Hospices Civils de Lyon, CHU-Lyon, 69003 Lyon, France
| | - Jérôme Dumortier
- Service d'Hépato-gastro-entérologie, Hôpital Edouard-Herriot, Hospices Civils de Lyon, 69003 Lyon, France
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Zoubek ME, Pinazo-Bandera J, Ortega-Alonso A, Hernández N, Crespo J, Contreras F, Medina-Cáliz I, Sanabria-Cabrera J, Sanjuan-Jiménez R, González-Jiménez A, García-Cortés M, Lucena MI, Andrade RJ, Robles-Díaz M. Liver injury after methylprednisolone pulses: A disputable cause of hepatotoxicity. A case series and literature review. United European Gastroenterol J 2019; 7:825-837. [PMID: 31316787 DOI: 10.1177/2050640619840147] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Accepted: 02/17/2019] [Indexed: 01/29/2023] Open
Abstract
Background and Objectives Corticosteroids are often empirically used to treat idiosyncratic hepatotoxicity with severe features. Interestingly, intravenous methylprednisolone (MP) is increasingly being recognized as being responsible for liver injury. We aimed to characterize MP-induced liver injury by analyzing demographical, clinical, laboratory and outcome data of three MP-induced hepatotoxicity cases and compared this information with that of previously published cases. Case series Three females with multiple sclerosis (MS) were treated intravenously with MP, mean daily dose 767 mg. Liver damage occurred 2 to 6 weeks after exposure. Severity was mild to moderate. Two patients suffered positive rechallenge. Literature review We identified 50 published cases of MP hepatotoxicity. Most of these cases were female (86%) and main treatment indications were MS (29 cases) and Graves' ophthalmopathy (13 cases). Hepatocellular damage predominated and mean time to onset was 6 weeks. Four patients died and rechallenge occurred in 19 cases. Conclusion MP pulses can induce severe liver injury, often with an autoimmune phenotype, particularly in patients with MS and Graves' ophthalmopathy. Consequently, these patient groups should have liver tests monitored when treated with MP to provide safer patient care.
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Affiliation(s)
- Miguel Eugenio Zoubek
- UGC Digestivo y Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), H U Virgen de la Victoria, Malaga, Spain.,Department of Toxicology, School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
| | - José Pinazo-Bandera
- UGC Digestivo y Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), H U Virgen de la Victoria, Malaga, Spain
| | - Aida Ortega-Alonso
- UGC Digestivo y Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), H U Virgen de la Victoria, Malaga, Spain
| | - Nelia Hernández
- Hospital de Clínicas, Clínica Gastroenterología, F Medicina, Montevideo, Uruguay
| | - Javier Crespo
- Unidad de Gestión Clínica de Enfermedades Digestivas, Hospital Marqués de Valdecilla, Instituto de Investigación Biomédica Marques de Valdecilla (IDIVAL), Santander, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Madrid, Spain
| | - Fernando Contreras
- Departamento de Gastroenterología, National University Pedro Henríquez Ureña, Santo Domingo, Dominican Republic
| | - Inmaculada Medina-Cáliz
- UGC Digestivo y Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), H U Virgen de la Victoria, Malaga, Spain
| | - Judith Sanabria-Cabrera
- UGC Digestivo y Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), H U Virgen de la Victoria, Malaga, Spain.,Unidad Investigación Clínica y Ensayos ClÚcos (UICEC)-Instituto de Investigacióe Biomedicina de Málaga (IBIMA), Plataforma Spanish Clinical Research Network (SCReN), Málaga Spain
| | - Rocío Sanjuan-Jiménez
- UGC Digestivo y Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), H U Virgen de la Victoria, Malaga, Spain.,Unidad Investigación Clínica y Ensayos ClÚcos (UICEC)-Instituto de Investigacióe Biomedicina de Málaga (IBIMA), Plataforma Spanish Clinical Research Network (SCReN), Málaga Spain
| | - Andrés González-Jiménez
- UGC Digestivo y Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), H U Virgen de la Victoria, Malaga, Spain
| | - Miren García-Cortés
- UGC Digestivo y Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), H U Virgen de la Victoria, Malaga, Spain
| | - M Isabel Lucena
- UGC Digestivo y Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), H U Virgen de la Victoria, Malaga, Spain.,Unidad Investigación Clínica y Ensayos ClÚcos (UICEC)-Instituto de Investigacióe Biomedicina de Málaga (IBIMA), Plataforma Spanish Clinical Research Network (SCReN), Málaga Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Madrid, Spain
| | - Raúl J Andrade
- UGC Digestivo y Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), H U Virgen de la Victoria, Malaga, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Madrid, Spain
| | - Mercedes Robles-Díaz
- UGC Digestivo y Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), H U Virgen de la Victoria, Malaga, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Madrid, Spain
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Nociti V, Biolato M, De Fino C, Bianco A, Losavio FA, Lucchini M, Marrone G, Grieco A, Mirabella M. Liver injury after pulsed methylprednisolone therapy in multiple sclerosis patients. Brain Behav 2018; 8:e00968. [PMID: 29729087 PMCID: PMC5991562 DOI: 10.1002/brb3.968] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Revised: 03/06/2018] [Accepted: 03/11/2018] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVES High-dose pulsed methylprednisolone-related liver injury cases have been reported in the literature, but a prospective study in patients with multiple sclerosis (MS) has never been performed. The aim of this study was to evaluate the prevalence and severity of liver injury in patients with MS after pulsed methylprednisolone therapy. METHODS We performed a prospective observational single-center study on patients with MS treated with i.v. methylprednisolone 1,000 mg/day for 5 days. We tested the liver functionality before and 2 weeks after the treatment. In case of severe liver injury, defined according to "Hy's law," a comprehensive hepatologic workup was performed. RESULTS During a 12-month observation period, we collected data on 251 cycles of i.v. steroid treatment of 175 patients with MS. After excluding eight cycles presenting a basal alteration of the biochemical liver tests, we observed a prevalence of 8.6% of liver injury in MS patients treated with pulsed methylprednisolone for clinical and neuroradiological relapses. In 2.5% of the patients, the liver injury was severe according to Hy's law; after a comprehensive hepatologic workup, three of them received a diagnosis of drug-induced liver injury and the other three of autoimmune hepatitis. CONCLUSIONS Liver injury after pulsed methylprednisolone therapy in patients with MS is not infrequent, and a close monitoring of aminotransferase level before treatment and 2 weeks later seems advisable.
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Affiliation(s)
- Viviana Nociti
- Multiple Sclerosis CenterNeuroscience Area, Neuroscience, Aging, Head and Neck and Orthopaedics Sciences DepartmentFondazione Policlinico Universitario GemelliCatholic University of Sacred HeartRomeItaly
- Fondazione Don Gnocchi‐ONLUSMilanItaly
| | - Marco Biolato
- Liver Transplant Medicine UnitGastroenterological Area, Gastroenterological and Endocrino‐Metabolical Sciences DepartmentFondazione Policlinico Universitario GemelliCatholic University of Sacred HeartRomeItaly
| | - Chiara De Fino
- Multiple Sclerosis CenterNeuroscience Area, Neuroscience, Aging, Head and Neck and Orthopaedics Sciences DepartmentFondazione Policlinico Universitario GemelliCatholic University of Sacred HeartRomeItaly
| | - Assunta Bianco
- Multiple Sclerosis CenterNeuroscience Area, Neuroscience, Aging, Head and Neck and Orthopaedics Sciences DepartmentFondazione Policlinico Universitario GemelliCatholic University of Sacred HeartRomeItaly
| | - Francesco Antonio Losavio
- Multiple Sclerosis CenterNeuroscience Area, Neuroscience, Aging, Head and Neck and Orthopaedics Sciences DepartmentFondazione Policlinico Universitario GemelliCatholic University of Sacred HeartRomeItaly
| | - Matteo Lucchini
- Multiple Sclerosis CenterNeuroscience Area, Neuroscience, Aging, Head and Neck and Orthopaedics Sciences DepartmentFondazione Policlinico Universitario GemelliCatholic University of Sacred HeartRomeItaly
| | - Giuseppe Marrone
- Liver Transplant Medicine UnitGastroenterological Area, Gastroenterological and Endocrino‐Metabolical Sciences DepartmentFondazione Policlinico Universitario GemelliCatholic University of Sacred HeartRomeItaly
| | - Antonio Grieco
- Liver Transplant Medicine UnitGastroenterological Area, Gastroenterological and Endocrino‐Metabolical Sciences DepartmentFondazione Policlinico Universitario GemelliCatholic University of Sacred HeartRomeItaly
| | - Massimiliano Mirabella
- Multiple Sclerosis CenterNeuroscience Area, Neuroscience, Aging, Head and Neck and Orthopaedics Sciences DepartmentFondazione Policlinico Universitario GemelliCatholic University of Sacred HeartRomeItaly
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8
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Kim SJ, Ko WK, Jo MJ, Arai Y, Choi H, Kumar H, Han IB, Sohn S. Anti-inflammatory effect of Tauroursodeoxycholic acid in RAW 264.7 macrophages, Bone marrow-derived macrophages, BV2 microglial cells, and spinal cord injury. Sci Rep 2018; 8:3176. [PMID: 29453346 PMCID: PMC5816629 DOI: 10.1038/s41598-018-21621-5] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Accepted: 02/07/2018] [Indexed: 12/13/2022] Open
Abstract
This study aimed to investigate the anti-inflammatory effects of tauroursodeoxycholic acid (TUDCA) after spinal cord injury (SCI) in rats. We induced an inflammatory process in RAW 264.7 macrophages, BV2 microglial cells, and bone marrow-derived macrophages (BMM) using lipopolysaccharide (LPS). The anti-inflammatory effects of TUDCA on LPS-stimulated RAW 264.7 macrophages, BV2 microglial cells, and BMMs were analyzed using nitric oxide (NO) assays, quantitative real-time polymerase chain reactions (qRT-PCR), and enzyme-linked immunosorbent assays (ELISA). The pathological changes in lesions of the spinal cord tissue were evaluated by hematoxylin & eosin (H&E) staining, luxol fast blue/cresyl violet-staining and immunofluorescent staining. TUDCA decreased the LPS-stimulated inflammatory mediator, NO. It also suppressed pro-inflammatory cytokines of tumor necrosis factor-α (TNF-α), interleukin 1-β (IL-1β), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in both mRNA and protein levels. In addition, TUDCA decreased prostaglandin E2 (PGE2). After SCI, TUDCA supported the recovery of the injury site and suppressed the expression of inflammatory cytokines such as iNOS, CD68 and CD86. In addition, TUDCA induced the expression of anti-inflammatory cytokine, Arg-1. In conclusion, TUDCA inhibits inflammatory responses in RAW 264.7 macrophages, BV2 microglial cells, and BMMs. TUDCA can be a potential alternative drug for SCI.
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Affiliation(s)
- Seong Jun Kim
- Department of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Wan-Kyu Ko
- Department of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Min-Jae Jo
- Department of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Yoshie Arai
- Department of Biomedical Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Hyemin Choi
- Department of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Hemant Kumar
- Department of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - In-Bo Han
- Department of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, Gyeonggi-do, Republic of Korea.
| | - Seil Sohn
- Department of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, Gyeonggi-do, Republic of Korea.
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Dumortier J, Cottin J, Lavie C, Guillaud O, Hervieu V, Chambon-Augoyard C, Scoazec JY, Vukusic S, Vial T. Methylprednisolone liver toxicity: A new case and a French regional pharmacovigilance survey. Clin Res Hepatol Gastroenterol 2017; 41:497-501. [PMID: 28438569 DOI: 10.1016/j.clinre.2017.03.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Revised: 03/15/2017] [Accepted: 03/27/2017] [Indexed: 02/04/2023]
Abstract
Reported hepatotoxicity induced by corticosteroids is very rare, and the diagnosis is highly challenging in the context of auto-immune disease. We report here a case of high-dose methylprednisolone (MP)-induced acute hepatitis confirmed by liver histology in a patient with multiple sclerosis (MS) and a case series (n=4) notified to the French Pharmacovigilance center of Lyon. In all 5 cases, other common causes of hepatitis were excluded. The causal relationship with MP pulse therapy was supported by the fact that MP was the only culprit drug. In addition, 3 of these 5 patients underwent unintended single or multiple positive MP rechallenge. Our 5 patients scored a RUCAM score from 6 (probable) to 10 (highly probable). MP-induced liver injury is probably very rare, since only less than 30 cases have been reported in the literature. Nevertheless, our cases strongly illustrates that many cases could have been unrecognized; final diagnosis in 3 of 5 of our patients was made after the second or third episode of acute hepatitis. In conclusion, these cases we report here strongly illustrates that high-dose MP-induced liver injury can occur in patients treated for MS or auto-immune disorder. Unintended re-challenge can confirm the diagnosis and can help to distinguish it from autoimmune hepatitis. Performing liver function tests routinely both before and after MP administration would be beneficial, as the timely recognition of this complication and early drug withdrawal may prevent progression of severe necrosis hepatic injury.
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Affiliation(s)
- Jérôme Dumortier
- Service d'Hépato-gastro-entérologie, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France.
| | - Judith Cottin
- Centre de Pharmacovigilance, Service Hospitalo-Universitaire de Pharmacotoxicologie, Hospices Civils de Lyon, Lyon, France
| | - Caroline Lavie
- Université Claude Bernard Lyon 1, Lyon, France; Service de Neurologie A, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France
| | - Olivier Guillaud
- Service d'Hépato-gastro-entérologie, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Valérie Hervieu
- Université Claude Bernard Lyon 1, Lyon, France; Service d'anatomopathologie, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | | | - Jean-Yves Scoazec
- Service d'anatomopathologie, Institut Gustave Roussy, Villejuif, France
| | - Sandra Vukusic
- Université Claude Bernard Lyon 1, Lyon, France; Service de Neurologie A, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France
| | - Thierry Vial
- Centre de Pharmacovigilance, Service Hospitalo-Universitaire de Pharmacotoxicologie, Hospices Civils de Lyon, Lyon, France
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10
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Hidalgo de la Cruz M, Miranda Acuña JA, Lozano Ros A, Vega Catalina M, Salinero Paniagua E, Clemente Ricote G, De Andrés Frutos CD, Martínez Ginés ML. Hepatotoxicity after high-dose intravenous methylprednisolone in multiple sclerosis patients. Clin Case Rep 2017; 5:1210-1212. [PMID: 28781825 PMCID: PMC5538224 DOI: 10.1002/ccr3.1033] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Revised: 05/05/2017] [Accepted: 05/13/2017] [Indexed: 11/09/2022] Open
Abstract
Hepatotoxicity is a rare adverse event of methylprednisolone that should be considered in clinical practice. In patients at risk, we propose liver function surveillance, by measuring hepatic enzymes concentration 15-30 days after methylprednisolone administration. Additionally, we propose ACTH, dexamethasone, or plasma exchange as alternate treatment options for these patients.
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Affiliation(s)
| | | | - Alberto Lozano Ros
- Department of Neurology Gregorio Marañón General University Hospital Madrid Spain
| | - María Vega Catalina
- Department of Gastroenterology Gregorio Marañón General University Hospital Madrid Spain
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11
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Moleti M, Giuffrida G, Sturniolo G, Squadrito G, Campennì A, Morelli S, Puxeddu E, Sisti E, Trimarchi F, Vermiglio F, Marinò M. Acute liver damage following intravenous glucocorticoid treatment for Graves' ophthalmopathy. Endocrine 2016; 54:259-268. [PMID: 27003434 DOI: 10.1007/s12020-016-0928-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 03/14/2016] [Indexed: 12/17/2022]
Abstract
PURPOSE Over the last years, there have been several reports on the occurrence of acute liver damage (ALD) in patients affected with Graves' ophthalmopathy (GO) receiving intravenous glucocorticoids (ivGCs). This article is aimed at reviewing the literature on this specific topic and reporting two new cases of ALD occurring in GO patients while on ivGCs. METHODS The terms "glucocorticoid therapy" and "Graves' Ophthalmopathy"/"Graves' Orbitopathy"/"Thyroid eye disease" were used both separately and in conjunction with the terms "liver disease," "liver damage," "hepatotoxicity," "liver failure," to search MEDLINE for articles published since the first report of ALD in 2000 and up to 2015. RESULTS ALD [defined as an increase in alanine aminotransferase (ALT) >300 U/L] during or after completion of ivGCs has been so far reported in 17 fully documented cases. Overall, one-half of those patients were diagnosed as having autoimmune hepatitis (AIH) and in the vast majority of the remaining cases a diagnosis of methylprednisolone(MP)-induced hepatotoxicity was suspected. The clinical course of liver injury varied from asymptomatic hypertransaminasemia in the vast majority of patients to fatal hepatic failure in four patients receiving higher (>8 g) cumulative doses of MP. CONCLUSIONS The overall risk of ALD is relatively low (~1 %), and seems higher using a single dose >0.5 g and a cumulative dose >8.5 g MP. Whenever ivGC treatment is required, serum liver enzymes, viral hepatitis markers, and autoantibodies related to AIH should be obtained prior to ivGC administration. Liver function should be monitored during ivGC and up to 6 months after the end of treatment. Prolonging observation after 6 months is likely unnecessary, since all cases of ALD so far reported always occurred well within this term.
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Affiliation(s)
- Mariacarla Moleti
- Dipartimento di Medicina Clinica e Sperimentale, University of Messina, Messina, Italy.
| | - Giuseppe Giuffrida
- Dipartimento di Medicina Clinica e Sperimentale, University of Messina, Messina, Italy
| | - Giacomo Sturniolo
- Dipartimento di Medicina Clinica e Sperimentale, University of Messina, Messina, Italy
| | - Giovanni Squadrito
- Dipartimento di Patologia Umana dell'adulto e dell'età evolutiva, University of Messina, Messina, Italy
| | - Alfredo Campennì
- Dipartimento di Scienze Radiologiche, Sezione di Medicina Nucleare University of Messina, Messina, Italy
| | - Silvia Morelli
- Dipartimento di Medicina, University of Perugia, Perugia, Italy
| | - Efisio Puxeddu
- Dipartimento di Medicina, University of Perugia, Perugia, Italy
| | - Eleonora Sisti
- Dipartimento di Medicina Clinica e Sperimentale, University of Pisa, Pisa, Italy
| | - Francesco Trimarchi
- Dipartimento di Medicina Clinica e Sperimentale, University of Messina, Messina, Italy
| | - Francesco Vermiglio
- Dipartimento di Medicina Clinica e Sperimentale, University of Messina, Messina, Italy
| | - Michele Marinò
- Dipartimento di Medicina Clinica e Sperimentale, University of Pisa, Pisa, Italy
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12
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Kadle MAH, Mazurchik NV. Hepatotoxicity Induced by High Dose of Methylprednisolone Therapy in a Patient with Multiple Sclerosis: A Case Report and Brief Review of Literature. ACTA ACUST UNITED AC 2016. [DOI: 10.4236/ojgas.2016.65019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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13
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Davidov Y, Har-Noy O, Pappo O, Achiron A, Dolev M, Ben-Ari Z. Methylprednisolone-induced liver injury: Case report and literature review. J Dig Dis 2016; 17:55-62. [PMID: 26676833 DOI: 10.1111/1751-2980.12306] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Accepted: 12/13/2015] [Indexed: 12/11/2022]
Affiliation(s)
- Yana Davidov
- Liver Disease Center.,Institute of Gastroenterology
| | - Ofir Har-Noy
- Liver Disease Center.,Institute of Gastroenterology
| | | | - Anat Achiron
- Multiple Sclerosis Center, Sheba Medical Center, Tel HaShomer, Ramat Gan.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Mark Dolev
- Multiple Sclerosis Center, Sheba Medical Center, Tel HaShomer, Ramat Gan
| | - Ziv Ben-Ari
- Liver Disease Center.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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14
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Carrier P, Godet B, Crepin S, Magy L, Debette-Gratien M, Pillegand B, Jacques J, Sautereau D, Vidal E, Labrousse F, Gondran G, Loustaud-Ratti V. Acute liver toxicity due to methylprednisolone: consider this diagnosis in the context of autoimmunity. Clin Res Hepatol Gastroenterol 2013; 37:100-4. [PMID: 23318289 DOI: 10.1016/j.clinre.2012.10.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2012] [Revised: 10/07/2012] [Accepted: 10/17/2012] [Indexed: 02/04/2023]
Abstract
The occurrence of corticosteroid-induced hepatitis is a rare event that has been recently described in the literature. We report the case of an acute cytolytic hepatitis in a patient treated with methylprednisolone for multiple sclerosis associated with an autoimmune thyroid dysfunction. After ruling out other etiologies, we concluded that the acute liver injury was due to steroids, and we analyzed the specific circumstances in the literature where methylprednisolone may have been responsible for acute hepatitis.
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Affiliation(s)
- P Carrier
- Service d'hépato-gastroentérologie, CHU de Limoges, 2, avenue Martin-Luther-King, 87042 Limoges, France.
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15
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Xu HM, Chen Y, Xu J, Zhou Q, Yoon SK, Kim DG, You YK, Choi MG, Han SW. Drug-induced liver injury in hospitalized patients with notably elevated alanine aminotransferase. World J Gastroenterol 2012; 18:5972-8. [PMID: 23139615 PMCID: PMC3491606 DOI: 10.3748/wjg.v18.i41.5972] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2012] [Revised: 05/31/2012] [Accepted: 06/08/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify the proportion, causes and the nature of drug-induced liver injury (DILI) in patients with notably elevated alanine aminotransferase (ALT).
METHODS: All the inpatients with ALT levels above 10 times upper limit of normal range (ULN) were retrospectively identified from a computerized clinical laboratory database at our hospital covering a 12-mo period. Relevant clinical information was obtained from medical records. Alternative causes of ALT elevations were examined for each patient, including biliary abnormality, viral hepatitis, hemodynamic injury, malignancy, DILI or undetermined and other causes. All suspected DILI cases were causality assessed using the Council for International Organizations of Medical Sciences scale, and only the cases classified as highly probable, probable, or possible were diagnosed as DILI. Comments related to the diagnosis of DILI in the medical record and in the discharge letter for each case were also examined to evaluate DILI detection by the treating doctors.
RESULTS: A total of 129 cases with ALT > 10 ULN were identified. Hemodynamic injury (n = 46, 35.7%), DILI (n = 25, 19.4%) and malignancy (n = 21, 16.3%) were the top three causes of liver injury. Peak ALT values were lower in DILI patients than in patients with hemodynamic injury (14.5 ± 5.6 ULN vs 32.5 ± 30.7 ULN, P = 0.001). Among DILI patients, one (4%) case was classified as definite, 19 (76%) cases were classified as probable and 5 (20%) as possible according to the CIOMS scale. A hepatocellular pattern was observed in 23 (92%) cases and mixed in 2 (8%). The extent of severity of liver injury was mild in 21 (84%) patients and moderate in 4 (16%). Before discharge, 10 (40%) patients were recovered and the other 15 (60%) were improved. The improved patients tended to have a higher peak ALT (808 ± 348 U/L vs 623 ± 118 U/L, P = 0.016) and shorter treatment duration before discharge (8 ± 6 d vs 28 ± 12 d, P = 0.008) compared with the recovered patients. Twenty-two drugs and 6 herbs were found associated with DILI. Antibacterials were the most common agents causing DILI in 8 (32%) cases, followed by glucocorticoids in 6 (24%) cases. Twenty-four (96%) cases received treatment of DILI with at least one adjunctive drug. Agents for treatment of DILI included anti-inflammatory drugs (e.g., glycyrrhizinate), antioxidants (e.g., glutathione, ademetionine 1,4-butanedisulfonate and tiopronin), polyene phosphatidyl choline and herbal extracts (e.g., protoporphyrin disodium and silymarin). Diagnosis of DILI was not mentioned in the discharge letter in 60% of the cases. Relative to prevalent cases and cases from wards of internal medicine, incident cases and cases from surgical wards had a higher risk of missed diagnosis in discharge letter [odds ratio (OR) 32.7, 95%CI (2.8-374.1), and OR 58.5, 95%CI (4.6-746.6), respectively].
CONCLUSION: DILI is mostly caused by use of antibacterials and glucocorticoids, and constitutes about one fifth of hospitalized patients with ALT > 10 ULN. DILI is underdiagnosed frequently.
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16
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SHAHSHAHANI MM, AZIZAHARI S, SOORI T, MANAVI S, BALIGHI K, DANESHPAZHOOH M, DAVATCHI CS, ESMAILI N. Hepatotoxicity and liver enzyme alteration in patients with immunobullous diseases receiving immunosuppressive therapy. J Dermatol 2011; 38:1153-7. [DOI: 10.1111/j.1346-8138.2011.01278.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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17
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Liver Injury Induced by High-Dose Methylprednisolone Therapy: A Case Report and Brief Review of the Literature. HEPATITIS MONTHLY 2011. [DOI: 10.5812/kowsar.1735143x.641] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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18
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19
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Bolus de méthylprednisolone révélant une hépatite auto-immune chez une patiente atteinte de sclérose en plaques. ACTA ACUST UNITED AC 2009. [DOI: 10.1007/s12157-009-0116-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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20
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Toscano E, Cotta J, Robles M, Lucena MAI, Andrade RJ. [Hepatotoxicity induced by new immunosuppressants]. GASTROENTEROLOGIA Y HEPATOLOGIA 2009; 33:54-65. [PMID: 19889479 DOI: 10.1016/j.gastrohep.2009.07.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2009] [Accepted: 07/02/2009] [Indexed: 01/24/2023]
Abstract
Immunosuppressants are among the pharmacological agents with the greatest potential to cause adverse reactions, although induction of hepatotoxicity is paradoxical from the pathogenic point of view, since the response of the innate and acquired immune system is a key element in the chain of events leading to chemical liver damage. Hepatotoxicity induced by immunosuppressants is difficult to evaluate since these drugs are sometimes used to treat liver diseases, or in combination with other drugs that can also cause hepatotoxicity, or in the context of liver transplantation, in which rejection or biliary complications can act as confounding factors. In addition, immunosuppressant therapy can favor the development of infections, which by themselves can cause liver damage, or reactivate latent chronic viral hepatitis. Corticosteroids and calcineurin inhibitors only exceptionally cause hepatotoxicity. Methotrexate at high doses and in patients with risk factors can induce advanced fibrosis and cirrhosis. Thiopurine agents can cause a spectrum of hepatic lesions, including hepatocellular of cholestatic lesions, and hepatic vascular alterations. Leflunomide has high hepatotoxic potential, especially when combined with methotrexate. Anti-tumor necrosis factor-alpha agents have rarely been associated with hepatotoxicity, often with detectable autoantibodies, and most of the reactions - some severe - have been linked to infliximab, especially when used in patients with rheumatological diseases.
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Affiliation(s)
- Elena Toscano
- Departamento de Medicina, Universidad de Málaga, Málaga, España
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21
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Tajiri K, Shimizu Y. Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol 2009. [PMID: 19058303 DOI: 10.3748/wig.14.6774] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The spectrum of drug-induced liver injury (DILI) is both diverse and complex. The first step in diagnosis is a suspicion of DILI based on careful consideration of recent comprehensive reports on the disease. There are some situations in which the suspicion of DILI is particularly strong. Exclusion of other possible etiologies according to the pattern of liver injury is essential for the diagnosis. In patients with suspected DILI, diagnostic scales, such as the Councils for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM) scale, may be helpful for the final diagnosis. Early management of DILI involves prompt withdrawal of the drug suspected of being responsible, according to serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (T-Bil). However, as DILI patients may show resolution of liver injury without discontinuation of the drug, it should be carefully evaluated whether the suspected drug should be discontinued immediately with adequate consideration of the importance of the medication.
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Affiliation(s)
- Kazuto Tajiri
- Department of Gastroenterology and Hematology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan
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22
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Tajiri K, Shimizu Y. Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol 2008; 14:6774-6785. [PMID: 19058303 PMCID: PMC2773872 DOI: 10.3748/wjg.14.6774] [Citation(s) in RCA: 132] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2008] [Revised: 11/05/2008] [Accepted: 11/12/2008] [Indexed: 02/06/2023] Open
Abstract
The spectrum of drug-induced liver injury (DILI) is both diverse and complex. The first step in diagnosis is a suspicion of DILI based on careful consideration of recent comprehensive reports on the disease. There are some situations in which the suspicion of DILI is particularly strong. Exclusion of other possible etiologies according to the pattern of liver injury is essential for the diagnosis. In patients with suspected DILI, diagnostic scales, such as the Councils for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM) scale, may be helpful for the final diagnosis. Early management of DILI involves prompt withdrawal of the drug suspected of being responsible, according to serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (T-Bil). However, as DILI patients may show resolution of liver injury without discontinuation of the drug, it should be carefully evaluated whether the suspected drug should be discontinued immediately with adequate consideration of the importance of the medication.
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Affiliation(s)
- Kazuto Tajiri
- Department of Gastroenterology and Hematology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan
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23
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Tajiri K, Shimizu Y. Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol 2008. [PMID: 19058303 DOI: 10.4748/wjg.14.6774] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The spectrum of drug-induced liver injury (DILI) is both diverse and complex. The first step in diagnosis is a suspicion of DILI based on careful consideration of recent comprehensive reports on the disease. There are some situations in which the suspicion of DILI is particularly strong. Exclusion of other possible etiologies according to the pattern of liver injury is essential for the diagnosis. In patients with suspected DILI, diagnostic scales, such as the Councils for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM) scale, may be helpful for the final diagnosis. Early management of DILI involves prompt withdrawal of the drug suspected of being responsible, according to serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (T-Bil). However, as DILI patients may show resolution of liver injury without discontinuation of the drug, it should be carefully evaluated whether the suspected drug should be discontinued immediately with adequate consideration of the importance of the medication.
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Affiliation(s)
- Kazuto Tajiri
- Department of Gastroenterology and Hematology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan
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24
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Ah YM, Kim YM, Kim MJ, Choi YH, Park KH, Son IJ, Kim SG. Drug-induced Hyperbilirubinemia and the Clinical Influencing Factors. Drug Metab Rev 2008; 40:511-37. [DOI: 10.1080/03602530802341133] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Abstract
PURPOSE OF REVIEW To summarize the pertinent literature on the causes, epidemiology, prevalence, clinical features, evaluation and mechanisms of drug-induced liver injury reported during 2007. RECENT FINDINGS Although the frequency of drug-induced liver injury remains low, new data from the Centers for Disease Control and Prevention confirm that of the approximately 1600 new acute liver failure cases annually, acetaminophen hepatotoxicity accounts for 41%; among children with acute liver failure, acetaminophen was the second most common cause. Antimicrobials lead the list of non-acetaminophen causes of drug-induced liver injury. In Asia, herbal compounds are the most common causes of the condition. Pravastatin was shown to be safe in patients with nonalcoholic fatty liver disease or chronic hepatitis C. The US Food and Drug Administration issued a draft guidance document on the premarketing clinical evaluation and stopping rules of drug-induced liver injury signals, including Hy's Law cases in clinical trials. SUMMARY The year 2007 brought with it several reminders of the importance of drug-induced liver injury in the clinical trial as well as the clinical practice setting. There is additional evidence that statin drugs may be used safely in patients with chronic liver disease. Comments received by the US Food and Drug Administration to finalize their guidance document are eagerly awaited.
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26
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Loh CH, Liou SH, Chang YW, Chen HI, Perng WC, Ku HY, Chen YH. Hepatic injuries of hexachloroethane smoke inhalation: the first analytical epidemiological study. Toxicology 2008; 247:119-22. [PMID: 18417266 DOI: 10.1016/j.tox.2008.02.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2008] [Revised: 02/21/2008] [Accepted: 02/21/2008] [Indexed: 11/16/2022]
Abstract
UNLABELLED There has been no human epidemiological data regarding the hepatic injuries of hexachloroethane-zinc oxide (HC/ZnO) inhalation. This is the first epidemiological study to investigate whether HC/ZnO inhalation exposure can induce hepatic dysfunction in exposed soldiers. Twenty soldiers, exposed to high concentration of HC/ZnO smoke for 3-10 min in a narrow tunnel (0.6 m in width) during military training, were recruited as exposed group and they were divided into high-exposed group (n=10) and low-exposed group (n=10) by the distance from the explosion locale as a surrogate of exposure condition. Another 64 soldiers, not visiting the explosion areas, were recruited as referents. Venous blood was collected for liver function analyses. After log transformation of alanine aminotransferase (ALT) and adjustment for potential confounders, serum ALT in high-exposed soldiers was statistically significantly higher than those of referents for the 3 weeks following exposure. The serum ALT in low exposed soldiers was statistically significantly higher than those of referents at the 3rd week following exposure. The mean ALT levels also showed decreasing gradients by the distance from exposure locale. In addition, the proportions of abnormality on ALT (>40U/L) were also significantly different among three exposure conditions. Follow-up study showed that the hepatic dysfunction started from 1 to 2 weeks and peaked from 3rd to 5th week after exposure. ALT level was then returned to normal within 6-8 weeks after removing from HC/ZnO smoke exposure. No sequelas in hepatic dysfunction were found until 72 weeks follow-up. CONCLUSION We concluded that inhalation of HC/Zn smoke can induce acute, dose-dependent and definite temporal relationship hepatic dysfunction.
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Affiliation(s)
- Ching-Hui Loh
- Department of Family Medicine and Community Health, Tri-service General Hospital, National Defense Medical Center, No. 325, Cheng-Kung Road, Sec. 2, Neihu 114, Taipei, Taiwan.
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27
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Current World Literature. Curr Opin Rheumatol 2008; 20:111-20. [DOI: 10.1097/bor.0b013e3282f408ae] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Elefsiniotis IS, Liatsos GD, Stamelakis D, Moulakakis A. Case report: mixed cholestatic/hepatocellular liver injury induced by the herbicide quizalofop-p-ethyl. ENVIRONMENTAL HEALTH PERSPECTIVES 2007; 115:1479-1481. [PMID: 17938739 PMCID: PMC2022636 DOI: 10.1289/ehp.9968] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/08/2006] [Accepted: 08/23/2007] [Indexed: 05/25/2023]
Abstract
CONTEXT Quizalofop-p-ethyl is an often applied, slightly toxic herbicide for which no severe toxicity has been reported in humans. CASE PRESENTATION We present the case of a farmer exposed to quizalofop-p-ethyl who presented with obstructive cholestasis. A complete workup disclosed no other cause of liver pathology, but liver biopsy established drug-induced hepatotoxicity. The patient was treated with ursodeoxycholic acid and prednisolone, and was recovered fully 70 days after his exposure to the herbicide. The patient was followed for the next 9 months. CONCLUSION Quizalofop-p-ethyl can induce a mixed cholestatic/hepatocellular liver injury. We discuss possible mechanisms implicated in liver injury after exposure to quizalofop-p-ethyl. RELEVANCE TO CLINICAL OR PROFESSIONAL PRACTICE In patients presenting with mixed cholestatic/ hepatocellular liver injury, occupational exposure to quizalofop-p-ethyl in the course of agricultural use should be investigated.
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Affiliation(s)
| | - George D. Liatsos
- Address correspondence to G.D. Liatsos, Department of Internal Medicine, “Hippokration” General Hospital, Vasilissis Sofias 114, TK 11527, Athens, Greece. Telephone: 30-213-2088342. Fax: 30-210-7787807. E-mail:
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Abstract
PURPOSE OF REVIEW To identify the key publications of 2006 dealing with drug-induced liver injury. RECENT FINDINGS When given in therapeutic doses over 14 days, acetaminophen produced significant asymptomatic elevations in alanine aminotransferase among healthy volunteers, suggesting that subclinical injury may be more common than previously thought. Acute liver failure in children was shown to differ in several important respects from that seen in adults, notably a much lower incidence of acetaminophen toxicity with nearly half of all cases being indeterminate in origin. The first cases of hepatotoxicity with telithromycin, a new class of ketolide antibiotic, were described along with reports suggesting liver injury from ezetimibe among other agents. The potential for chronic injury to develop after acute drug-induced liver injury was analyzed in a large Swedish database; 5-6% of cases were judged to become chronic, with drugs causing cholestatic injury predominating. Among well described hepatotoxins, new reports appeared with highly active antiretroviral therapy agents, herbal therapies and several antibiotics. Finally, the safe use of pravastatin and pioglitazone was demonstrated in patients with chronic liver disease in controlled clinical trials. SUMMARY Drug-induced liver injury remains an important concern for many existing drugs as well as for agents in development.
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Affiliation(s)
- Cherinne Arundel
- Division of Gastroenterology, Section of Hepatology, Georgetown University Medical Center, Washington, DC 20007, USA
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John Wiley & Sons, Ltd.. Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiol Drug Saf 2007. [DOI: 10.1002/pds.1374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Loraschi A, Mauri M, Bono G, Lecchini S, Cosentino M. Two Cases of Hepatotoxicity Following High-Doses Methylprednisolone Therapy for Demyelinating Diseases. Drug Saf 2007. [DOI: 10.2165/00002018-200730100-00141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
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