Hepatotoxicity

Drug-induced liver injury (DILI) is classified as: hepatocellular (elevated ALT >3× ULN, indicating hepatocyte damage), cholestatic (elevated ALP >2× ULN, indicating bile duct/flow impairment), or mixed pattern. Hy's Law (FDA) identifies cases at highest risk of severe outcomes: ALT >3× ULN + bilirubin >2× ULN without cholestasis or other cause — this combination predicts approximately 10-50% risk of fatal liver failure. Liver function monitoring (ALT, AST, ALP, bilirubin) is standard in clinical trials and post-marketing for most drugs. For peptide drugs, hepatotoxicity is less common than with small molecules because peptides are not metabolised by CYP450 enzymes (a major source of reactive metabolite-mediated liver injury). However, some peptide drugs affect liver-related pathways: somatostatin analogues can cause gallstones (inhibiting gallbladder contraction), and pasireotide can cause hyperglycaemia (hepatic glucose metabolism effects).