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How to make steatotic livers suitable for transplantation

Improvements in the surgical and nonsurgical care of patients with end-stage liver disease have led to an expansion of the indications for liver transplantation, resulting in an increasing shortage of donor organs. Despite many attempts to expand the donor pool, such as utilizing split or living donor liver transplants, the amount of available organs is insufficient to meet the demand. Alternatives to human organs, such as bioartificial organs, xenotransplantation, or stem-cell technology do not appear to have widespread clinical applicability in the foreseeable future. It seems logical, therefore, to focus attention on organs from compromised donors—organs that are at a higher risk of postoperative complications, such as initial poor graft function (or even primary nonfunction) or biliary complications. Although there is no general consensus on the definition of a compromised, or extended-criteria, donor, most would include donors who are older ( 60 years), and who have diabetes mellitus, hypertension, renal insufficiency, or hepatic steatosis in this category. Obesity, diabetes mellitus, the metabolic syndrome, and associated nonalcoholic fatty liver disease are reaching epidemic proportions throughout the world. A recent survey has indicated that up to 30% of the population in Western societies has a certain degree of hepatic steatosis. In case of advanced degrees of steatosis, this condition may preclude certain individuals as liver donors. Although some controversy about whether all steatotic livers should be excluded from transplantation remains, and some groups have reported reasonable outcomes utilizing livers with a certain degree of steatosis, livers that are deemed steatotic are frequently discarded. The reason not to utilize a potential liver is frequently based on subjective findings of hepatic steatosis during the procurement of postmortem organs, and in most programs, potential living donors are excluded when hepatic steatosis is detected during routine preoperative evaluation. There is a growing body of evidence to argue that steatotic livers are more susceptible to ischemia-reperfusion injury and, following transplantation, have less favorable outcomes than nonsteatotic livers. Hence, if manipulations, in vivo or ex vivo, could increase the quality of these organs and improve their outcome following transplantation, the number of livers available for transplantation would increase and, thereby, reduce current waiting lists for liver transplantation. These manipulations can be divided into 2 groups, the first focusing on reversing hepatic steatosis. If reversal cannot be achieved, the other group can focus on protecting the liver from ischemia-reperfusion injury associated with steatosis. In this issue of Liver Transplantation, Bessems et al. present their data on hypothermic machine preservation of fatty livers in a rodent model of hepatic steatosis. On the basis of an elegant and well-documented study, the authors conclude that less liver damage is observed following machine preservation of steatotic livers in comparison to conventional storage and that hepatobiliary function is superior in livers preserved with machine perfusion. Although the experiments