Hepatotoxicity

Hepatotoxicity describes liver injury caused by drugs, chemicals, or biological agents, ranging from mild elevations in liver enzymes to severe liver failure requiring transplantation. This toxicity may arise through direct cellular damage, immune-mediated mechanisms, mitochondrial dysfunction, or formation of reactive metabolites. Hepatotoxicity represents a leading cause of clinical trial failure and post-market withdrawals.

The pharmaceutical industry prioritises hepatotoxicity assessment throughout development due to its significant safety implications. Preclinical studies evaluate liver effects through histopathology, clinical chemistry markers, and mechanistic assays predicting injury risk. Clinical trials monitor liver function tests closely, applying stopping rules and risk management strategies when signals emerge. Drug-induced liver injury investigation requires careful causality assessment and consideration of class effects. Regulatory agencies expect robust hepatic safety monitoring plans and appropriate labelling for identified risks. As predictive toxicology advances through human-relevant models and biomarkers, hepatotoxicity management remains central to developing safe therapies.