Non-Alcoholic Fatty Liver Disease: Investigating the Impact of Bariatric Care and the Role of Immune Function

Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis (SS) to nonalcoholic steatohepatitis (NASH) and cirrhosis. It is one of the most common causes of chronic liver disease resulting from obesity. 74-98% of morbidly obese individuals have NAFLD at the time of bariatric surgery. Post-bariatric surgery, NAFLD significantly improves but some patients continue to have persistent disease, particularly fibrosis. The pathogenesis of NAFLD is complex. In addition to insulin resistance, recent research suggests a potential role for liver immune function and intestinal microbiota (IM). The objectives of this research were 1) to prospectively evaluate the impact of bariatric care on metabolic and liver histology parameters by studying two bariatric care interventions: the routinely prescribed pre-operative very-low calorie diet (VLCD) and the Roux-en-Y gastric bypass (RYGB); and 2) to explore in a cross-sectional study whether there are differences in liver immune cells between NAFLD and healthy subjects and whether there are associations with intestinal microbiota (IM). Specifically, the plan was to assess: 1) liver histology post-VLCD and factors associated with NAFLD; 2) the effects of RYGB on liver histology and the factors associated with persistent NAFLD at 12-months post-RYGB; 3) liver immune cell counts in NAFLD compared to controls and the association between these cell counts and IM. We found that at the time of surgery (post-VLCD), the prevalence of NAFLD was low, likely due to the effect of the VLCD. Those with NASH had higher insulin resistance and presence of diabetes prior to the diet. At 12-months post-RYGB there were further improvements in anthropometry, metabolic measurements and liver histology. However, those with persistent NAFLD had less improvement in waist circumference and glycemic control. The cross-sectional study showed that specific liver immune cells, namely CD163, CD20 and CD45 were significantly increased in NAFLD versus controls and that immune cell counts were significantly correlated with specific bacterial taxa. In conclusion, both VLCD and RYGB have beneficial effects on metabolic and histological parameters but those with persistent NAFLD are more metabolically impaired despite similar interventions. Other potential mechanisms, such as a potential interplay between IM and liver immune cells, require further investigation.Ph.D