Metabolic biomarkers as predictors of Nash recurrence after liver transplant

In recent years, non-alcoholic fatty liver disease (NALFD) emerged as one of the most common chronic diseases in the United States. NAFLD can range from simple hepatic steatosis to the more severe nonalcoholic steatohepatitis (NASH), which can result in fibrosis and cirrhosis. Since NASH was assigned a diagnostic category for transplant in 2001, it has demonstrated the greatest increase of new liver transplant (LT) waitlist registrants and is currently a leading indication for LT. Redevelopment of steatosis after LT occurs in up to 40% of LT recipients; however, there is still a lack of knowledge on the prevalence and risk factors of steatosis in LT recipients transplanted for NASH. Thus, increasing our understanding on these predictors is critical to the development of clinical practice guidelines to improve patient monitoring and prevent disease recurrence in NASH patients in the post-transplant setting. My previous work identified a significant role crosstalk of lipid subspecies between the liver and adipose tissue that is critical for the development NASH in rodents. This established a causal role of ceramides, a lipid species with signaling capabilities, in driving the accumulation of lipids in the liver and hepatic insulin resistance. In this proposal, I will build on my previous studies and test the hypothesis that 1) serum lipid species are a biomarker of hepatic health and a predictor or disease recurrence risk post-LT, and 2) adipose tissue health is a critical determinant of recurrence of hepatic steatosis following LT. The proposed analyses will uncover a link between lipid species, adipose tissue metabolic health, and liver disease recurrence post-LT that will inform future steatosis prevention and clinical management practices post-LT.