Drug-induced liver injury drugs

Boelsterli, U. A. 1993. Specific targets of covalent drug-protein interactions and their toxicological significance in drug-induced liver injury. Drug Metabolism Review 25 395 51. 

Ekins S, WiUiams AJ, Xu JJ (2010) A predictive ligand-based Bayesian model for human drug-induced liver injury. Drug Metab Dispos 38, 2302—8. 

Pessayre D, Fromenty B, Berson A, Robin MA, Letteron P, Moreau R, Mansouri A (2012) Central role of mitochondria in drug-induced liver injury. Drug Metab Rev 44, 34-87. 

Corsini, A., et al.. Current challenges and controversies in drug-induced liver injury. Drug Saf, 2012. 35(12) p. 1099-117. 

D. (1991). The decrease of superoxide dismutase activity and depletion of sulfhydryl compounds in ethanol-induced liver injury. Drug Alcohol Depend. 28, 291-294. 

Reprinted from J Gin Epidemiol, Vol 46, Danan C, Benichou C. Causality assessment of adverse reactions to drugs-4. A novel method based on the conclusions of international consensus meetings- Application to drug-induced liver injuries pages 1323-1330, Copyright 1993, with permission from Elsevier. 

We call attention also to the web site for the Drug-Induced Liver Injury Network (DILIN) sponsored since 2003 by the National Institutes of Health (NIH), Liver Disease Branch of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). 

Lammert, C., Einarsson, S., Saha, C Niklasson, A., Bjornsson, E. and Chalasani, N. (2008) Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury search for signals. Hepatology (Baltimore, Md), 47, 2003-2009. 

The best clinical evidence that BSEP is involved in hepatotoxicity is provided by human genetic studies which found four highly conserved non-synonymous mutations in two hepatobiliary transporters (BSEP and MDR3) that were specific for drug-induced liver injury [118]. Recently, a consortium of investigators identified a remarkable 82 different ABCBll mutations in 109 families that caused severe BSEP deficiency [119]. It is therefore expected that at least some of these genetic mutations and polymorphisms will put patients at an increased risk of drug-induced cholestasis. Does this justify the implementation of a simple BSEP inhibition screen for all new chemical entities The answer is not quite that simple. 

Many patients have underlying liver disease with liver function abnormalities. It may be difficult to determine superimposed drug-induced liver injury in patients with viral hepatitis, passive congestion of the liver from heart failure, fatty liver... 

Lang, C. et al. (2007) Mutations and polymorphisms in the bde salt e5q)ort pump and the multidrug resistance protein 3 assodated with drug-induced liver injury. Pharmacogenet Genomics,... 

EDA (2007) Guidance for Industry Drug-Induced Liver Injury Premarketing Clinical Evaluation (draft document). 

Bleibel, W., Kim, S., D Silva, K. and Lemmer, E.R. (2007) Drug-induced liver injury review article. Digestive Disease and Sciences, 52, 2463—2471. 

The incidence of drug-induced liver injury with rosiglitazone has been calculated at 0.02% for alanine transaminase activity 10 times the upper end of the reference range and 0.001% for jaundice (120). The above case report is unusual because, although liver damage is rare, hepatic necrosis occurs more commonly than cholestatic hepatitis. 

Slavin DE, Schlichting CL, Freston JW. Rating the severity of the medical consequences of drug-induced liver injury. Regulatory Toxicol Pharmacol 2005 43 134-40. 

Mitchell, J.R., et al. Metabolic activation - Biochemical basis for many drug-induced liver injuries. Prog Liver Dis, 1976 5 259-279... 

Table 3.4 Examples of types of drug-induced liver injury and associated drugs...

Weden [27] described a protracted cholestasis which was thought to be induced by the use of a COC. The patient s liver biopsy revealed changes including eosinophilia and sinusoidal dilatation, which could be linked to a drug-induced liver injury. The cholestasis gradually disappeared, but an elevated serum alkaline phosphatase level continued for up to ten years after discontinuation of the COC [27]. Another paper has discussed oestrogen-induced cholestasis and highlights the link between the use of COCs and intrahepatic cholestasis... 

Watkins, P.B., Seef, L.B. (2006). Drug-induced liver injury summary of a single topic clinical research committee. Hepatology 43 618-31. 

DIAGNOSIS AND MANAGEMENT OF DRUG-INDUCED LIVER INJURY... 

Sasada T, Koizumi M, Matsumoto M, Takegawa T, Kikukawa M, Oku K, Kitazawa T, Nishimura K, Kosima H, Vemura M, Fukui H. A case of drug-induced liver injury caused by mequitazine. Acta Hepatol Jpn 1999 40 541-5. 

Penicillin-induced hepatotoxicity may not be as uncommon as has been thought. There have been three reviews. The first was a comparison of the assessment of drug-induced liver injury obtained by two different methods, the Council for International Organizations of Medical Sciences (CIOMS) scale and the Maria Victorino (M V) clinical scale (66). Three independent experts evaluated 215 cases of hepatotoxicity reported using a structured reporting form. There was absolute agreement between the two scales in 18% of cases, but there was no agreement in cases of fulminant hepatitis or death. The authors concluded that the CIOMS instrument is more likely to lead to a conclusion compatible with the specialist s empirical approach. 

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