Autophagy impairment and ERK and p38 activation are central mediators of irinotecan-induced steatohepatitis

Treatment with irinotecan is associated with the development of chemotherapy-associated steatohepatitis (CASH), which significantly increases the risk of perioperative morbidity and mortality. The aim of this study was to unravel the molecular mechanisms of this phenomenon. Methods: Mechanisms of irinotecan induced steatohepatitis were studied in primary human hepatocytes in vitro, irinotecan treated mice and liver specimens from irinotecan-treated patients. Results: Irinotecan dose-dependently induced accumulation of free fatty acids and triglycerides, formation of reactive oxygen species (ROS), pro-inflammator…