Development of an in vitro liver model for prediction of drug-induced liver injury

MPS World Summit 2026 -- Drug-induced liver injury (DILI) remains a critical challenge in pharmaceutical development, frequently leading to clinical trial failure and post-market drug withdrawal. Preclinical animal models often fail to predict human hepatotoxicity, with estimates suggesting that nearly half of DILI-related drug failures are not anticipated during preclinical testing. New approach methodologies (NAMs) are designed to improve human-relevant toxicity assessment. Recent regulatory initiatives further encourage the adoption of alternatives to animal testing. Different in vitro hepatocyte models are available ranging from 2D cell line to complex 3D systems. In this study, a HepG2 2D cell line was used to differentiate compounds with varying DILI risk. Six compounds were assessed, four hepatotoxins and two non‑hepatotoxic compounds. Compounds were classified into three DILI severity categories: most DILI concern, less DILI concern, and no DILI concern.