Pharmacological advances in liver transplantation and resection

This thesis, which includes clinical and laboratory research, was meant to advance liver surgery thanks to pharmacology. Since immunosuppression, as well as rejection, is detrimental, we investigated in adult liver transplantation whether induction with depleting antibodies helps minimise immunosuppression after one year. Early histological rejection was attenuated. As organ shortage and increasing indications widen the gap between supply and demand, there is little alternative to live-donor liver transplantation. Managing a small-for-size liver in the donor or in recipient remains a challenge, where hypoxia-signalling pathways play a role. Can hypoxia gene signature be induced by means of a pharmacological stabilisation of its downstream transducers? We studied the histological and functional changes caused by roxadustat, a selective stabiliser of these transcription factors, in a model of liver resection. The drug reduced steatosis and ballooning, markers of hepatocellular injury.