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 (NAFLD) has progressively increased. Non-alcoholic steatohepatitis (NASH), a subtype of NAFLD has also augmented considerably being currently cirrhosis due to NASH the second indication for liver transplantation in USA. 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 wait list and the organ shortage has obligated the transplant centres to consider suboptimal grafts, such as steatotic livers for transplantation. Fatty livers are vulnerable to preservation injury resulting in a higher rate of primary non-function, early allograft dysfunction and post-transplant 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. Authors contributed equally to this paper, Ivan Linares MD, Matyas Hamar MD. Correspondence author: Markus Selzner, MD, Associate Professor of Surgery, University of Toronto, General Surgery & Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, 585 University Avenue, 11 PMB 178, Toronto, ON M5G 2N2, Phone: 416-340-4800 ext. 5884 Fax: 416-340-5321, e-mail: markus.selzner@uhn.ca Authorship: -Ivan Linares participated in performance of research, research design and writing the paper (lin85ij@outlook.com) -Matyas Hamar participated in performance of research, research design and writing the paper (mahamar@gmail.com) -Nazia Selzner participated in research design and writing the paper (Nazia.Selzner@uhn.ca) -Markus Selzner participated in research design and writing the paper (Markus.Selzner@uhn.ca) Disclosure: The authors of this manuscript have no conflicts of interest to disclose as described by the Transplantation Journal. Funding: None Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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