On-Site PhD conferral Kim M.C. van Mierlo

Key words: postoperative liver failure, liver regeneration, chemotherapy-induced liver injury, composite endpoint

"Postoperative liver (dys)function: determinants and interventions"

This thesis investigated determinants of and interventions for liver (dys)function after liver surgery for liver cancer. Three main topics were addressed. Firstly, the impact of chemotherapy-associated liver injury on complications after liver surgery for colorectal liver metastases was assessed. It was shown that chemotherapy-associated liver injury led to an increased complication rate after liver surgery. Secondly, current endpoints to define and detect liver failure after liver surgery were investigated. Despite the broad use of definitions and surrogate endpoints, analysis of multiple studies showed that there is little evidence on their validity as true surrogates of clinical endpoints. Lastly, the role of bile salts in liver failure and liver regeneration after liver surgery was examined. Several studies showed that bile salts seem a culprit in liver failure, and that bile salt homeostasis during liver regeneration is already optimal in partial hepatectomy in rodents.

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