Grant: Operating Grant

Minimal hepatic encephalopathy (MHE) is a serious complication of liver disease characterized by cognitive, psychiatric and motor disturbances that can lead to coma and death. As much as 80% of patients with cirrhosis suffer from MHE, of which the burden is immense, considering its impact on the patients, their families and society. To date, liver transplantation (LT) is the only curative treatment that has demonstrated to prolong the lives of patients with end-stage liver disease. However, the development of neurological complications (NC) following LT is an arising problem in transplanted patients. We hypothesize that the presence of MHE at the time of LT is an important factor involved in NC observed post-LT. In addition, given that LT is a major surgical procedure associated with excessive blood loss that leads to hypotension, the latter may be responsible for the neurological impairment that develops post-LT in patients with MHE. Thus, we argue that patients with MHE may be more susceptible to cerebral damage following a hypotensive insult. In view of this, we will study the metabolism of lactate, brain edema and the newly identified lactate G-protein-coupled receptor (GPR81), and conduct a prospective study of patients with end-stage liver disease who are to receive a new liver, in order to better evaluate the impact of MHE and the pathogenic factors on neurological impairment following LT. Results of this study will clarify the respective roles of lactate, brain edema and GPR81 in the pathogenesis of MHE-sensitive neurological damage resulting from hypotension, and emphasize the importance of treating MHE before LT. Finally, as the pathogenic factors are identified, insights for new therapeutic strategies will be uncovered, not only to help improve the quality of life of liver disease patients with MHE on the LT waiting list, but also to lead to a better neurological outcome after following LT.