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.

Keywords: Hepatotoxicity; Predictivity; Risk assessment; Safety

Core tip: The interest in drug-induced liver injury (DILI) is growing, especially in 2015-2016, with pioneering studies addressing DILI annotation, i.e., risk stratification of drugs capable of causing liver damage. The latest experiences from worldwide consortia provided promising data, although there is still room for improvement before reaching an algorithm capable of discriminating hepatotoxic from non-hepatotoxic compounds, or at least of classifying high, intermediate and low risk drugs within the same therapeutic class. We should take advantage of integration of real-world data (i.e., registries, healthcare databases, spontaneous reporting systems, literature) with cheminformatics to provide a comprehensive DILI risk score.