| Summary: | Over 80% of patients undergoing bariatric surgery have non-alcoholic fatty liver diseas (NAFLD), including a third with steatohepatitis. Fatty livers are vulnerable to toxic insults, including ischaemia-reperfusion injury (IRI) and inflammation. The induction of pneumoperitoneum and retraction of the liver during laparoscopic surgery causes an acute inflammatory response and IRI. In this thesis, twenty patients were recruited to a randomised controlled trial of N9 acetylcysteine (NAC), an antioxidant, given before and during laparoscopic sleeve gastrectomy (LSG) to reduce liver injury and post-operative inflammatory response. The acute effects of LSG were investigated, with measurement of cytokines, markers of hepatocyte death and oxidative stress. The results showed that NAC did not significantly reduce the rise in liver enzymes or improve clinical outcomes. Further assays demonstrated that a significant inflammatory and oxidative stress insult occurs, with increases in markers such as C-reactive protein, IL-6, superoxide dismutase and cytokeratin-18 (CK-18) fragments, indicative of hepatocyte death. These markers returned to baseline within 48 hours. The patients were followed for 6 months and the result of longitudinal changes are described, showing significant reduction in BMI, along with reductions in insulin resistance, inflammatory markers and CK-18. Bile acid (BA) metabolism was also studied, showing a significant increase in fibroblast growth factor 19 levels, indicating a likely increase in bile delivery to the terminal ileum after LSG, which was associated with significant changes in four conjugated BA, although total BA was unchanged. These changes correlated with reduction in inflammatory markers and hepatocyte death. In onclusion, LSG is associated with a short-term inflammatory response and liver injury. After 6 months, the relevant markers fall below baseline, indicating improvement in inflammatory profile, glycaemic control and extent of NAFLD. Further work is needed to understand these relationships in a larger sample of patients undergoing a variety of bariatric operations.
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