Cholesterol regulatory genes predict liver transplant outcomes

Liver transplantation, or LT, is a life-saving therapy for patients with end-stage liver disease. End-stage liver disease develops from chronic liver diseases like metabolic dysfunction-associated steatotic liver disease, or MASLD, and metabolic dysfunction-associated steatohepatitis, or MASH, which is an advanced form of MASLD.

Recent organ donation statistics show that 10,659 liver transplants were performed in 2023, and the 1-year and 5-year survival rates after LT are 85% and 75%, respectively. Because MASLD affects roughly one-quarter of the general population and MASH is the second leading cause of LT in the US, screening organ donors for these conditions before transplant is essential to ensure patient safety and outcomes.

In a recent study published in the Journal of Lipid Research, Anna Baulies, Carmen García-Ruiz and a team of researchers in Spain investigated lipid content and expression of cholesterol metabolic genes in liver grafts, healthy tissue used for transplant, before and after the procedure, to predict patient survival and health outcomes. They collected liver biopsy samples from patients undergoing LT and found that increased free cholesterol and free fatty acid levels, as well as increased expression of the cholesterol regulatory genes SREBF2 and HMGCR in liver grafts prior to transplant, increased the risk of early allograft dysfunction, graft loss and in some cases, even death after transplant.

The correlation between cholesterol regulatory genes and LT-related mortality can inform donor screening for chronic liver disease, ensuring that healthier donor organs are selected to increase transplant success and, in turn, improve outcomes for patients receiving life-saving livers.