Novel in vitro model for combined effects of irinotecan and free fatty acids on hepatocellular lipid accumulation and inflammation

Preoperative chemotherapy with irinotecan is associated with the development of chemotherapy-associated steatohepatitis (CASH). Epidemiological studies have shown that irinotecan-treated obese patients have a higher risk to develop CASH and subsequent related mortality. However, the underlying mechanisms of these aggravated effects of irinotecan in hepatic steatosis are still unknown. The aim of this study was to establish an in vitro model of irinotecan-induced CASH in normal and steatotic hepatocytes and to unravel the molecular mechanisms of this phenomenon. Methods and Results: Initially, we determined the d…