Drug-induced liver injury

被引:553
作者
Andrade, Raul J. [1 ,2 ]
Chalasani, Naga [3 ]
Bjornsson, Einar S. [4 ,5 ]
Suzuki, Ayako [6 ,7 ]
Kullak-Ublick, Gerd A. [8 ,9 ]
Watkins, Paul B. [10 ,11 ]
Devarbhavi, Harshad [12 ]
Merz, Michael [8 ,13 ]
Isabel Lucena, M. [2 ,14 ]
Kaplowitz, Neil [15 ]
Aithal, Guruprasad P. [16 ,17 ]
机构
[1] Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Unidad Gest Clin Enfermedades Digest, Malaga, Spain
[2] Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
[3] Indiana Univ Sch Med, Div Gastroenterol, Indianapolis, IN 46202 USA
[4] Univ Iceland, Landspitali Univ Hosp Reykjav, Dept Gastroenterol, Reykjavik, Iceland
[5] Univ Iceland, Fac Med, Reykjavik, Iceland
[6] Duke Univ, Gastroenterol, Durham, NC USA
[7] Durham VA Med Ctr, Gastroenterol, Durham, NC USA
[8] Univ Zurich, Univ Hosp Zurich, Dept Clin Pharmacol & Toxicol, Zurich, Switzerland
[9] Novartis Pharmaceut, Mechanist Safety CMO & Patient Safety, Global Drug Dev, Basel, Switzerland
[10] Univ N Carolina, UNC Eshelman Sch Pharm, Chapel Hill, NC 27515 USA
[11] Univ N Carolina, Inst Drug Safety Sci, Chapel Hill, NC 27515 USA
[12] St Johns Med Coll Hosp, Dept Gastroenterol & Hepatol, Bangalore, Karnataka, India
[13] AstraZeneca, Patient Safety, Gaithersburg, MD USA
[14] Univ Malaga, Serv Farmacol Clin, Inst Invest Biomed Malaga IBIMA, Hosp Univ Virgen de la Victoria, Malaga, Spain
[15] Keck Sch Med, Div Gastroenterol & Liver Dis, Dept Med, Los Angeles, CA USA
[16] Nottingham Univ Hosp NHS Trust, Natl Inst Hlth Res, Nottingham Digest Dis Biomed Res Ctr, Nottingham, England
[17] Univ Nottingham, Nottingham, England
关键词
SALT EXPORT PUMP; STEVENS-JOHNSON SYNDROME; SINGLE-CENTER EXPERIENCE; CAUSALITY ASSESSMENT; IN-VITRO; RISK-FACTORS; ACETAMINOPHEN HEPATOTOXICITY; GLUTAMATE-DEHYDROGENASE; IDIOPATHIC AUTOIMMUNE; EPIDERMAL NECROLYSIS;
D O I
10.1038/s41572-019-0105-0
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
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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页数:22
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