Living donor liver transplantation (LDLT) has been developed to provide an alternative source of grafts to overcome the problem of organ shortages. Although the donor selection and evaluation process and the surgical techniques are completely different for LDLT and deceased donor liver transplantation, it is generally agreed that recipients' disease indications should be similar. Nonetheless, there are some controversial indications for LDLT, and among these indications, acute liver failure (ALF) has generated several debatable issues. First, several initial reports (mainly from Western countries) showed inferior outcomes with LDLT in high-urgency situations. Second, in countries in which deceased organ donation is well developed, patients with ALF, who are given top priority on the waiting list, have a high chance of receiving a liver graft in time. The role and justification of LDLT are thus questionable. Third, there are serious concerns about (1) the coercion of donors in such urgent situations and (2) possible increases in risks to donors due to the limited time for thorough evaluations.
These 3 issues have to be discussed in the context of the availability of deceased organ donors. The marked differences in the organ donation rates of Western and Asian countries have driven the development of LDLT in different directions, and this partly accounts for the debates about LDLT. The number of deceased donors per million people is less than 6 in most Asian countries, but in the West, the number is 3 to 4 times higher (or even more). LDLT accounts for less than 5% of liver transplants in the United States and Europe but for more than 90% of liver transplants in Asia (excluding mainland China).1 Japan has the lowest number of brain-dead donors in Asia, and a study by the Kyoto group2 has indicated that there is frequently a perceived reality of no choice among living liver donors; this is particularly true in the desperately urgent situation of ALF.
In this issue of Liver Transplantation, Yamashiki et al.3 report the largest cohort of patients undergoing LDLT for ALF (n = 209), and they address the issue of long-term outcomes. These patients were identified from a nationwide survey database of 1090 patients with ALF in Japan over a period of 11 years, and the survival data were extracted from a separate database of the Japan Liver Transplantation Registry. The outcomes were excellent and included 1- and 5-year patient survival rates of 79% and 74%, respectively; these rates were comparable to national data on deceased donor liver transplantation for ALF in Western countries.4 Yamashiki et al. also confirmed on a larger scale the excellent outcomes of previous case series of LDLT for ALF from individual high-volume centers in Asia5-7 as well as the multicenter Adult-to-Adult Living Donor Liver Transplantation Cohort Study in the United States.8 Multicenter studies using national databases are important for determining whether the experiences of individual high-volume centers can be generalized. In addition, this study has the advantage of a larger case number, which increased its power for statistical analyses such as the identification of prognostic factors. By now, there should be enough evidence to refute the suggestion that partial grafts from living donors are marginal and may result in inferior outcomes for high-urgency patients with ALF.
Yamashiki et al.3 did not specifically address the role and justification of LDLT for ALF. Previous studies from Korea and Hong Kong,5, 9 however, have shown that less than 10% of listed patients with ALF in Asia will receive a deceased donor liver transplant. The overall wait-list mortality rate is 45% to 60%, and this rate is markedly reduced if there is a potential living donor who has undergone an evaluation. Japan has an even lower deceased donor rate than Hong Kong and Korea. There were only 3 deceased donor liver transplants for ALF over an 11-year period, and 209 of 212 transplants (98.6%) for ALF came from living donors: this strongly indicates that there is no choice but LDLT in Japan. This contrasts sharply with the findings of the Adult-to-Adult Living Donor Liver Transplantation Cohort Study from the United States,8 which recorded only 10 LDLT procedures for ALF in 9 liver transplant centers over a 9-year period. LDLT for ALF is rarely needed in the West.
The third issue of concern—the coercion and safety of living donors—is important because the average time from listing to LDLT was only 4 days in the current study from Japan. Experienced liver transplant programs in Asia that perform emergency LDLT for ALF have developed protocols and logistics for fast-track evaluations of living donors; these include, for example, 24-hour radiology, endoscopy, and clinical psychology assessments and even legal support for fulfilling the requirements of law. To allow extra time for the process, the discussion of LDLT and the preliminary donor evaluation may start early, even before the criteria for transplantation are fulfilled. To prevent any additional risks for the donor, it is crucial to adhere closely to such protocols and criteria for donor evaluations with few exceptions.
LDLT is a strategy that allows the optimal timing of transplantation for ALF, and it may potentially lead to better outcomes. The rapidly progressive course of ALF provides only a very narrow window for liver transplantation, and even in the United States, there is a wait-list mortality rate greater than 20%.10 The timing of deceased donor liver transplantation is dictated entirely by the availability of a liver graft, which may come too early or too late. In addition, because of the urgency, high-risk marginal grafts are frequently used with poor outcomes. In contrast, LDLT not only permits early transplantation and thus can prevent wait-list mortality but also allows better control of the timing of the transplant operation. If the donor evaluation and the preparation for transplantation can be finished before the patient is listed, a graft can conceivably be in hand and the transplant can be performed at the first sign of deterioration. Furthermore, the quality of a living donor graft is uniformly good, and this allows the rapid reversal of the acute disease process. Such a strategy may prove to be advantageous for patients with ALF even in countries in which deceased donor liver transplantation is more readily available. LDLT for ALF has developed in Asia because there is no choice. Is it possible that it may in fact be a better choice?