Pharmacotherapies for Drug-Induced Liver Injury: A Current Literature Review

Drug-induced liver injury (DILI) has become a serious public health problem. For the management of DILI, discontinuation of suspicious drug or medicine is the first step, but the treatments including drugs and supporting approaches are needed. Reference to clinical patterns and disease severity grades of DILI, the treatment drugs were considered to summarize into hepatoprotective drugs (N-acetylcysteine and Glutathione, Glycyrrhizin acid preparation, Polyene phosphatidylcholine, Bicyclol, Silymarin), anticholestatic drug (Ursodeoxycholic acid, S-adenosylmethionine, Cholestyramine), immunosuppressants (Glucocorticoids) and specific treatment agents (L-carnitine, Anticoagulants). The current article reviewed the accumulated literature with evidence-based medicine researches for DILI in clinical practice. Also the drawbacks of the clinical studies involved in the article, unmet needs and prospective development for DILI therapy were discussed.

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Evidence-based selection of training compounds for use in the mechanism-based integrated prediction of drug-induced liver injury in man

Archives of Toxicology ◽

10.1007/s00204-016-1845-1 ◽

2016 ◽

Vol 90 (12) ◽

pp. 2979-3003 ◽

Cited By ~ 24

Author(s):

Sanja Dragovic ◽

Nico P. E. Vermeulen ◽

Helga H. Gerets ◽

Philip G. Hewitt ◽

Magnus Ingelman‐Sundberg ◽

...

Keyword(s):

Liver Injury ◽

Evidence Based ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Selection Of

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Performance of preclinical models in predicting drug-induced liver injury in humans: a systematic review

Scientific Reports ◽

10.1038/s41598-021-85708-2 ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Hubert Dirven ◽

Gunn E. Vist ◽

Sricharan Bandhakavi ◽

Jyotsna Mehta ◽

Seneca E. Fitch ◽

...

Keyword(s):

Liver Injury ◽

Adverse Events ◽

Adverse Drug Reactions ◽

Evidence Based ◽

Drug Reactions ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Vitro Data ◽

In Vitro Data

AbstractDrug-induced liver injury (DILI) causes one in three market withdrawals due to adverse drug reactions, causing preventable human suffering and massive financial loss. We applied evidence-based methods to investigate the role of preclinical studies in predicting human DILI using two anti-diabetic drugs from the same class, but with different toxicological profiles: troglitazone (withdrawn from US market due to DILI) and rosiglitazone (remains on US market). Evidence Stream 1: A systematic literature review of in vivo studies on rosiglitazone or troglitazone was conducted (PROSPERO registration CRD42018112353). Evidence Stream 2: in vitro data on troglitazone and rosiglitazone were retrieved from the US EPA ToxCast database. Evidence Stream 3: troglitazone- and rosiglitazone-related DILI cases were retrieved from WHO Vigibase. All three evidence stream analyses were conducted according to evidence-based methodologies and performed according to pre-registered protocols. Evidence Stream 1: 9288 references were identified, with 42 studies included in analysis. No reported biomarker for either drug indicated a strong hazard signal in either preclinical animal or human studies. All included studies had substantial limitations, resulting in “low” or “very low” certainty in findings. Evidence Stream 2: Troglitazone was active in twice as many in vitro assays (129) as rosiglitazone (60), indicating a strong signal for more off-target effects. Evidence Stream 3: We observed a fivefold difference in both all adverse events and liver-related adverse events reported, and an eightfold difference in fatalities for troglitazone, compared to rosiglitazone. In summary, published animal and human trials failed to predict troglitazone’s potential to cause severe liver injury in a wider patient population, while in vitro data showed marked differences in the two drugs’ off-target activities, offering a new paradigm for reducing drug attrition in late development and in the market. This investigation concludes that death and disability due to adverse drug reactions may be prevented if mechanistic information is deployed at early stages of drug development by pharmaceutical companies and is considered by regulators as a part of regulatory submissions.

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Leberschaden unter oraler Antikoagulation, Statin- und ACE-Hemmertherapie

Praxis ◽

10.1024/1661-8157/a000298 ◽

2010 ◽

Vol 99 (21) ◽

pp. 1259-1265 ◽

Cited By ~ 2

Author(s):

Bruggisser ◽

Terraciano ◽

Rätz Bravo ◽

Haschke

Keyword(s):

Liver Injury ◽

Wird Eine ◽

Drug Induced ◽

Drug Induced Liver Injury

Ein 71-jähriger Patient stellt sich mit Epistaxis und ikterischen Skleren auf der Notfallstation vor. Der Patient steht unter einer Therapie mit Phenprocoumon, Atorvastatin und Perindopril. Anamnestisch besteht ein langjähriger Alkoholabusus. Laborchemisch werden massiv erhöhte Leberwerte (ALAT, Bilirubin) gesehen. Der INR ist unter oraler Antikoagulation und bei akuter Leberinsuffizienz >12. Die weiterführenden Abklärungen schliessen eine Virushepatitis und eine Autoimmunhepatitis aus. Nachdem eine Leberbiopsie durchgeführt werden kann, wird eine medikamentös-toxische Hepatitis, ausgelöst durch die Komedikation von Atorvastatin, Phenprocoumon und Perindopril bei durch Alkohol bereits vorgeschädigter Leber diagnostiziert. Epidemiologie, Pathophysiologie und Klink der medikamentös induzierten Leberschäden (drug induced liver injury, DILI), speziell von Coumarinen, Statinen und ACE-Hemmern werden im Anschluss an den Fallbericht diskutiert.

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