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• W2604524922 abstract "Drug-induced liver injury (DILI) is a major concern for patients, care givers and the pharmaceutical industry. Interpretation of the serum biomarkers routinely used to detect and monitor DILI, which have not changed in almost 50 years, can be improved with recently proposed models employing quantitative systems pharmacology. In addition, several newer serum biomarkers are showing great promise. Studies in rodents indicate that the ratio of the caspase cleaved fragment of cytokeratin 18 to total K18 in serum (termed the “apoptotic index”) estimates the relative proportions of apoptosis vs necrosis during drug-induced liver injury. Glutamate dehydrogenase can reliably differentiate liver from muscle injury and, when serum is properly prepared, may also detect mitochondrial toxicity as a mechanism of liver injury. MicroRNA-122 is liver-specific, but recent data suggests it can be actively released from hepatocytes in the absence of overt toxicity limiting enthusiasm for it as a DILI biomarker. Finally, damage associated molecular patterns, particularly high mobility group box 1 and its various modified forms, are promising biomarkers of innate immune activation, which may be useful in distinguishing benign elevations in aminotransferases from those that portend clinically important liver injury. These new biomarkers are already being measured in early clinical trials, but broad acceptance will require widespread archiving of serum from diverse clinical trials and probably pre-competitive analysis efforts. We believe that utilization of a panel of traditional and newer biomarkers in conjunction with quantitative systems pharmacology modelling approaches will transform DILI detection and risk management." @default.
• W2604524922 created "2017-04-14" @default.
• W2604524922 creator A5014115297 @default.
• W2604524922 creator A5062878299 @default.
• W2604524922 date "2017-05-08" @default.
• W2604524922 modified "2023-10-16" @default.
• W2604524922 title "The transformation in biomarker detection and management of drug-induced liver injury" @default.
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• W2604524922 doi "https://doi.org/10.1111/liv.13441" @default.
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