Drug-induced liver injury

被引:0
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作者
Raul J. Andrade
Naga Chalasani
Einar S. Björnsson
Ayako Suzuki
Gerd A. Kullak-Ublick
Paul B. Watkins
Harshad Devarbhavi
Michael Merz
M. Isabel Lucena
Neil Kaplowitz
Guruprasad P. Aithal
机构
[1] Hospital Universitario Virgen de la Victoria,Unidad de Gestión Clínica de Enfermedades Digestivas, Instituto de Investigación Biomédica de Málaga
[2] Universidad de Málaga,IBIMA
[3] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd),Division of Gastroenterology
[4] Indiana University School of Medicine,Department of Gastroenterology
[5] Landspitali University Hospital Reykjavik,Faculty of Medicine
[6] University of Iceland,Gastroenterology
[7] University of Iceland,Gastroenterology
[8] Duke University,Department of Clinical Pharmacology and Toxicology
[9] Durham VA Medical Centre,Mechanistic Safety, CMO & Patient Safety, Global Drug Development
[10] University Hospital Zurich,UNC Eshelman School of Pharmacy
[11] University of Zurich,Department of Gastroenterology and Hepatology
[12] Novartis Pharma,Patient Safety
[13] University of North Carolina,Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga
[14] University of North Carolina Institute for Drug Safety Sciences,IBIMA, Hospital Universitario Virgen de la Victoria, UICEC SCReN
[15] Research Triangle Park,Division of Gastroenterology and Liver Diseases, Department of Medicine
[16] St. John’s Medical College Hospital,National Institute for Health Research (NIHR) Nottingham Digestive Diseases Biomedical Research Centre
[17] AstraZeneca,undefined
[18] Universidad de Málaga,undefined
[19] Keck School of Medicine,undefined
[20] Nottingham University Hospital NHS Trust and University of Nottingham,undefined
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摘要
Drug-induced liver injury (DILI) is an adverse reaction to drugs or other xenobiotics that occurs either as a predictable event when an individual is exposed to toxic doses of some compounds or as an unpredictable event with many drugs in common use. Drugs can be harmful to the liver in susceptible individuals owing to genetic and environmental risk factors. These risk factors modify hepatic metabolism and excretion of the DILI-causative agent leading to cellular stress, cell death, activation of an adaptive immune response and a failure to adapt, with progression to overt liver injury. Idiosyncratic DILI is a relative rare hepatic disorder but can be severe and, in some cases, fatal, presenting with a variety of phenotypes, which mimic other hepatic diseases. The diagnosis of DILI relies on the exclusion of other aetiologies of liver disease as specific biomarkers are still lacking. Clinical scales such as CIOMS/RUCAM can support the diagnostic process but need refinement. A number of clinical variables, validated in prospective cohorts, can be used to predict a more severe DILI outcome. Although no pharmacological therapy has been adequately tested in randomized clinical trials, corticosteroids can be useful, particularly in the emergent form of DILI related to immune-checkpoint inhibitors in patients with cancer.
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