Steatosis in Liver Transplantation: Current Limitations and Future Strategies

In parallel with the pandemic of obesity and diabetes, the prevalence of nonalcoholic fatty liver disease has progressively increased. Nonalcoholic steatohepatitis (NASH), a subtype of nonalcoholic fatty liver disease has also augmented considerably being currently cirrhosis due to NASH the second indication for liver transplantation in the United States. Innovative treatments for NASH have shown promising results in phase 2 studies and are being presently evaluated in phase 3 trials. On the other hand, the high mortality on the liver transplant waitlist and the organ shortage has obligated the transplant centers to consider suboptimal grafts, such as steatotic livers for transplantation. Fatty livers are vulnerable to preservation injury resulting in a higher rate of primary nonfunction, early allograft dysfunction and posttransplant vascular and biliary complications. Macrosteatosis of more than 30% in fact is an independent risk factor for graft loss. Therefore, it needs to be considered into the risk assessment scores. Growing evidence supports that moderate and severe macrosteatotic grafts can be successfully used for liver transplantation with careful recipient selection. Protective strategies, such as machine-based perfusion have been developed in experimental setting to minimize preservation-related injury and are now on the verge to move into the clinical implementation. This review focuses on the current and potential future treatment of NASH and the clinical practice in fatty liver transplantation, highlights its limitations and optimal allocation, and summarizes the advances of experimental protective strategies, and their potential for clinical application to increase the acceptance and improve the outcomes after liver transplantation with high-grade steatotic livers.