Drug-induced liver injury: Towards early prediction and risk stratification

Abstract

Drug-induced liver injury (DILI) is a hot topic for clinicians, academia, drug companies and regulators, as shown by the steadily increasing number of publications and agents listed as causing liver damage (http://livertox.nih.gov/). As it was the case in the past decade with drug-induced QT prolongation/arrhythmia, there is an urgent unmet clinical need to develop tools for risk assessment and stratification in clinical practice and, in parallel, to improve prediction of pre-clinical models to support regulatory steps and facilitate early detection of liver-specific adverse drug events. Although drug discontinuation and therapy reconciliation still remain the mainstay in patient management to minimize occurrence of DILI, especially acute liver failure events, different multidisciplinary attempts have been proposed in 2016 to predict and assess drug-related risk in individual patients; these promising, albeit preliminary, results strongly support the need to pursue this innovative pathway.

Species differences in bile acids I. Plasma and urine bile acid composition

“…Similar to liver diseases, BA accumulation due to alterations of various aspects of their homeostasis by some drugs is proposed to be one of the major mechanisms underlying DILI (De Valle et al, ; Wagner et al, ). However, currently used in vitro and in vivo preclinical models of BA homeostasis fail to predict DILI in humans (Raschi & De Ponti, ). The marked differences in BA metabolism and homeostasis, and therefore their composition and toxicity between preclinical safety models and humans may explain the poor prediction of DILI at earlier stages of drug discovery and development.…”

Drug Induced Liver Disease

“…Host factors seem to have influence on DILD occurrence. DILD induced by DOACs therapy of venous thromboembolism in surgical patients is reported more frequently then atrial fibrilation [27].…”

Effectiveness of apixaban in warfarin hepatotoxicity: A case report

“…The mechanisms of warfarin and apixaban induced liver damage is unknown but has been suggested to be an idiosyncratic reaction [11,12].…”