Predicting Hepatotoxicity With The Liver-Chip

Join Dr. Jonathan Sexton in this informative webinar as he evaluates iPSC-derived human liver organoids (HLOs) for predicting drug-induced liver injury (DILI) risk. These HLOs autonomously generate hepatocytes, stellate, and Kupffer cells. The study uses Emulate Organ-Chips combined with a multi-omics approach—including metabolomics, single-cell RNA sequencing, and high-content imaging—to predict DILI risk and identify the mechanism of action.

Key findings include:

• HLOs on the Liver-Chip significantly increase albumin production and CYP450 expression.
• HLOs release ALT/AST when treated with DILI-causing drugs at clinically relevant concentrations.
• HLO Liver-Chips effectively evaluated inarigivir for hepatitis B, predicting hepatotoxicity in the tenofovir-inarigivir combination, which caused unexpected liver injury and death in a phase-III clinical study.
• This combination led to steatosis and mitochondrial perturbation in HLOs, mimicking the clinical and histological presentation of liver injury similar to fialuradine.

By watching webinar below, viewers will deepen their understanding of liver organoids and their pivotal role in enhancing DILI risk prediction through the use of advanced Organ-Chip technology.