A novel phenotype-based drug-induced liver injury causality assessment tool (DILI-CAT) allows for signal confirmation in early drug development.

ABSTRACT:

Background

Drug-induced liver injury (DILI) requires accurate case adjudication, with expert opinion being the current best practice.

Aim

We utilised a novel DILI causality assessment tool (DILI-CAT), which uses drug-specific liver injury phenotypes, to examine potential DILI in early phase ximelagatran clinical development.

Methods

We conducted a retrospective analysis of liver injury events from four Stroke Prevention using an ORal Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) trials, in which patients were randomised to receive oral ximelagatran or adjusted-dose warfarin. A stepwise process was used with iterative adjustments. The DILI phenotype was characterised by latency, R-value, and AST/ALT ratio. A scoring algorithm was applied to liver events to assess

SUBMITTER: Hermann RP 

PROVIDER: S-EPMC9164935 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature