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Con: Liver Transplantation Should Not Be Performed in Patients With Acute Alcoholic Hepatitis

2019; Lippincott Williams & Wilkins; Volume: 13; Issue: 5 Linguagem: Inglês

10.1002/cld.779

2046-2484

Jamil S. Alsahhar, Ashwini Mehta, Rita Lepe,

Diet, Metabolism, and Disease

Watch a video presentation of this article When considering acute alcoholic hepatitis (AAH) as a new indication for LT, it is important to understand how this will impact the waiting list. Based on the 2015 Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients (OPTN/SRTR) annual data report, there is an average of 15,000 patients on the waiting list at the start of any given year, with an additional 10,000 patients added throughout the year1 (Fig. 1). Of those waiting, roughly 6,000 receive transplants each year. About 1700 patients die annually while waiting on the list, with an additional 1200 removed because of being too sick for transplantation. When considering transplanting patients with AAH, we have to recognize that those patients are sick with high Model for End-Stage Liver Disease (MELD) scores, and thus will get priority if listed. Given that organs are scarce, adding patients with AAH to the list will not affect the number of transplants performed, but the number of patients dying while waiting on the list and those removed because of illness will increase. Hence it is paramount that such a change to current practices be approached with caution and uses the best available scientific evidence. United Network for Organ Sharing has set ethical principles guiding transplantation, including utility, justice, and respect for individuals.2 Utility refers to the fact that allocation of organs should provide the greatest benefit to all patients, thereby incorporating the principles of beneficence and nonmaleficence. Justice implies fairness in the pattern of distribution of benefits, risks, and costs of an organ procurement and allocation program. Justice does not only apply to a single person, but to all those who are on the waiting list. Using the best scientific evidence available ensures that organ allocation is accomplished ethically. Potts et al.3 evaluated the long-term outcomes in 109 patients admitted with AAH. The mortality rate during the index admission was 21%, with a cumulative 5-year survival rate of 32%. But when alcohol relapse was taken into account, patients who remained abstinent after their initial admission had a 5-year survival rate of 79%, whereas those who relapsed had a survival rate of 21% (Fig. 2). The high mortality rate was the same for patients who had an initial abstinence, then relapsed into alcohol. Based on their analysis, abstinence was the only independent predictor of survival (hazard ratio, 0.37; 95% confidence interval: 0.168-0.818; P = 0.014). As can be seen from these data, alcohol relapse is the main driver of long-term mortality after AAH. Thus, sobriety after AAH should be the major focus of research and resources. Many studies have evaluated the rate of alcohol relapse after LT and the associated long-term consequencs. Dumortier et al.4 evaluated 712 patients transplanted for alcoholic liver disease between 1990 and 2007, and found that 128 (18%) had relapsed into severe alcohol use. Among the patients who relapsed, about a third experienced recurrent alcoholic cirrhosis (RAC), and 26 patients (63.4%) with RAC died (Fig. 3), mainly from graft failure. After further analysis, younger age at transplantation and shorter pretransplantation sobriety were the main factors associated with severe alcoholic relapse and recurrent cirrhosis, both of which are risk factors in the majority of patients with AAH. The major push for LT in AAH followed the publication in the New England Journal of Medicine by Mathurin et al.5 In this landmark trial, stringent criteria were made to select 26 patients with SAH to undergo transplantation versus a control group. We would like to draw attention to three major issues in this study. First, the 6-month survival rate in the LT group was 77%. This survival rate, although higher than the control group, is much lower than the national 95% survival rate for liver disease of other causes. Five of the deaths occurred within the first 2 weeks after surgery, the majority of which were related to aspergillosis. Are we willing to accept these inferior rates of survival, especially when up to 30% of patients who are listed die annually while waiting for a new liver? The second concern is that 3 of the 13 patients with available follow-up data by 2 years had relapsed into alcohol use. We have to take into account that this was a “highly selected” group of patients who had an extensive screening process prior to LT. After counseling by an addiction specialist, two patients continued with heavy daily use of alcohol, and one drank occasionally. We come to the last and most important concern, which is the study design. One of the requirements for patients to be transplanted was that AAH was the first liver decompensating event, meaning that patients were never told that they had liver disease prior to their admission for AAH. This was not a criteria used for the control group. This is significant because patients who relapse to alcohol use after an episode of alcoholic hepatitis can have a more severe episode with a higher mortality rate (60%).6 Thus, the transplanted group and control group were different, and the survival benefit noted in this study is likely overestimated. Similar findings and concerns are raised when evaluating the study by Im et al.,7 in which nine patients were transplanted for AAH and compared with a control group. The controls were also a group who had known liver disease, whereas those transplanted had no known liver disease prior to their AAH admission, and hence the outcomes are likely exaggerated. Due to a limited resource, more information is needed to justify that patients with AAH are transplanted quicker because of a MELD point advantage over those who have been listed and compliant with medical follow-up. The 6-month sobriety rule is not perfect, but it does help observe high-risk patients, and data regarding risk for relapse cannot be ignored. The data on transplanting patients with AAH are limited, and until we have more information, early transplantation for AAH is not ready for primetime.