Liver Transplantation for Acute Liver Failure: Not Too Early But Never Too Late

Acute liver failure is a catastrophic illness that can rapidly progress to death in a previously healthy person with no known liver disease. Treatment is generally supportive, but the outcome is unpredictable. Although a variable proportion of patients can recover spontaneously, others may continue to deteriorate, and in such cases, liver transplantation is the only effective treatment. The rapidly progressive course of the disease, however, allows only a very narrow window for the application of liver transplantation. In order to avoid unnecessary transplants in those who would survive and to prevent unavailable transplants in those who would not survive, liver transplantation needs to be done at the optimal time, not too early but never too late. A2ALL, Adult-to-Adult Living Donor Liver Transplantation; LDLT, living donor liver transplantation. Unfortunately, the timing of deceased donor liver transplantation is dictated entirely by the availability of a liver graft. Various prognostic indicators have been suggested for the prediction of the outcome of acute liver failure to allow early identification and listing of those who would not survive without a transplant. In addition, patients with acute liver failure are generally given the top priority for graft allocation. Nonetheless, every transplant team must have faced the dilemma of whether to transplant an available graft into a patient with acute liver failure who has not yet fulfilled the criteria for transplantation or who has deteriorated to the point at which transplantation may be futile. Furthermore, as a last resort to save desperately ill patients, high-risk grafts such as extremely marginal or ABO-incompatible ones are frequently used, and this partly contributes to the inferior outcome of transplantation in these patients. In countries such as those in Asia where deceased organ donors are scarce, deceased donor liver transplantation is simply not an option at all. It was under such circumstances that the Hong Kong group initiated adult living donor liver transplantation (LDLT) using right lobe grafts in 1996.1 Since then, acute liver failure has generally been accepted as the prime indication for LDLT in Asia2-4 because it provides a unique opportunity for early transplantation and for controlling the timing of the transplant operation. Donor evaluation and preparation for transplant can be done at an early stage even before the criteria for transplantation are fulfilled and a graft is in hand so that the operation can be performed at the first sign of deterioration. Such a strategy may prove to be advantageous for critical patients with acute liver failure even in countries in which deceased donor liver transplantation is readily available. Furthermore, the quality of a living donor graft is uniformly good, allowing rapid reversal of the acute disease process. In this issue of Liver Transplantation, Campsen and colleagues5 report the outcome of patients with acute liver failure who were evaluated for LDLT within the Adult-to-Adult Living Donor Liver Transplantation (A2ALL) Cohort Study in the United States. Of the 1201 patients on the list for liver transplantation who had at least 1 potential living donor evaluated for liver donation at 9 liver transplant centers over a 9-year period, only 14 (1%) had a diagnosis of acute liver failure. Ten patients received LDLT, 3 underwent deceased donor liver transplantation, and 1 recovered spontaneously. Seven of 10 patients survived after LDLT, and 2 of 3 patients survived after deceased donor liver transplantation. There was no mortality in living donors, but 50% developed complications. The authors concluded that LDLT is rarely performed for acute liver failure in the United States but could be performed with acceptable recipient and donor outcomes. LDLT in adults is a novel operation full of controversy, and the A2ALL Study Group should be commended for its collaborative effort in accurately presenting the outcome of LDLT and critically evaluating its role in the United States. In this publication of the A2ALL Cohort Study, which is focused on the special indication of acute liver failure, the most striking finding is the rarity of patients with acute liver failure being considered for LDLT in the United States. Acute liver failure was the indication for transplantation in only 1% of the patients evaluated for LDLT in the current study versus about 5% of those who actually received liver transplantation in the United States.6 Because LDLT accounted for less than 5% of all liver transplants in the United States, the role of LDLT in the management of patients with acute liver failure was minimal. In fact, from 2002 to 2006, only 4 patients with acute liver failure were evaluated, and there was 1 and only 1 LDLT performed for acute liver failure in these 9 transplant centers over 5 years. This contrasted sharply with the role of LDLT for acute liver failure in Asia, where LDLT accounts for >90% of the liver transplants,7 and fulminant hepatic failure was the indication for transplantation in 5.7% of the adult LDLT series reported by the Asan group,4 in 12% of the series reported by the Hong Kong group,8 and in 14.6% of the series reported by the Kyoto group.9 Although this study shows a very minor role of LDLT for acute liver failure in the United States versus Asia, it provides support for the safety and efficacy of LDLT for acute liver failure, as previously reported from Asia. Donor morbidity was not excessive. The zero mortality on the waiting list was most remarkable in comparison with the 22% mortality rate reported in a prospective multicenter study in the United States10 and was undoubtedly attributable to the alternative option of LDLT. The average time from listing to donor evaluation of 2 days and then from donor evaluation to transplant of 2 days also demonstrated the ability of LDLT to reduce waiting time and provide optimal timing of transplantation. In experienced centers in Asia, the donor workups can even be completed in half a day.3 It has been suggested that the outcome of LDLT is inferior to that of deceased donor liver transplantation in high-urgency patients, and this has been attributed to the smaller size of a partial liver graft. Nonetheless, experience from Asia has indicated that if a graft with minimum volume and adequate venous drainage can be achieved, the survival after LDLT is at least comparable to that after deceased donor liver transplantation.2, 3 In fact, compared to patients with decompensated chronic liver disease, patients with acute liver failure might tolerate smaller grafts because there is no preexisting portal hypertension, and successful adult LDLT for acute liver failure using a graft of about 25% of the recipient's estimated standard liver volume has been reported.3 Concerns about both the added donor risk and inferior recipient outcome, which have led to the proscription of acute liver failure as an indication for LDLT in the New York Department of Health's guidelines, were not borne out in this A2ALL study. Nonetheless, the number of patients was small, and the power of the study was probably too low to generate enough assurance to change these guidelines. LDLT, as a strategy that potentially allows optimal timing of liver transplantation for acute liver failure, will continue to have a limited role in the United States.