Correspondence
Early Liver Transplantation for Severe Alcoholic Hepatitis
N Engl J Med 2012; 366:477-479February 2, 2012
- Article
To the Editor:
The study reported by Mathurin et al. (Nov. 10 issue)1 could have a strong impact on living-donor liver transplantation.
Mandatory alcohol abstinence before deceased-donor liver transplantation serves two purposes: evaluation of compliance, including the likelihood of recidivism, and reassurance to the public that the candidate has earned the right to a graft.2 Mathurin and colleagues challenged the former purpose, but not the latter, which concerns moral perceptions beyond evidence-based arguments.
In Far East regions, including Japan, deceased-donor organs remain scarce. Living-donor liver transplantation remains the mainstream approach, and the use of this procedure is different in the Far East than elsewhere. Without public restraints regarding the organ shortage, the expansion of indications is tempting, as shown in the case of hepatocellular carcinoma.3 Because abstinence has been mandated4 to establish compliance rather than to evoke a sense of justice, the study by Mathurin et al. calls for a reevaluation of the grounds of our current approach in living-donor liver transplantation, adding a further burden to the dilemma of living-donor liver transplantation.
Sumihito Tamura, M.D.
Yasuhiko Sugawara, M.D.
Norihiro Kokudo, M.D.
University of Tokyo Graduate School of Medicine, Tokyo, Japan
yasusugatky@yahoo.co. jp No potential conflict of interest relevant to this letter was reported.
4 References1
Mathurin P ,Moreno C ,Samuel D , et al. Early liver transplantation for severe alcoholic hepatitis. N Engl J Med 2011;365:1790-1800
Full Text | Web of Science | Medline2
Neuberger J ,Webb K . Liver transplantation for alcoholic liver disease: knowing the future informs the present. Am J Transplant 2010;10:2195-2196
CrossRef | Web of Science | Medline3
Todo S ,Furukawa H ,Tada M . Extending indication: role of living donor liver transplantation for hepatocellular carcinoma. Liver Transpl 2007;13:S48-S54
CrossRef | Web of Science | Medline4
Yamashiki N ,Sugawara Y ,Tamura S , et al. Selection of liver-transplant candidates for adult-to-adult living donor liver transplantation as the only surgical option for end-stage liver disease. Liver Transpl 2006;12:1077-1083
CrossRef | Web of Science | Medline
To the Editor:
From a practical standpoint, in areas where the demand for organs far exceeds availability, we would like to make the following observations. In spite of very strict selection criteria for early transplantation in the study reported by Mathurin et al., more than 10% of the patients still had alcohol relapse, with two remaining daily consumers at the end of the study. This rate of recidivism is significant, given the fact that the number of liver-transplant recipients represented fewer than 2% of patients with severe alcoholic hepatitis. There were also 6 deaths (of 26) in the recipient group, 5 of which occurred within 2 weeks after surgery. Thus, although there is improved survival with early transplantation, there is still a substantial risk of death. The findings of this study should instead prompt consideration of living-donor liver transplantation in a highly selected group of patients. This approach might act as an additional deterrent to recidivism while restricting the use of cadaveric organs for a still controversial indication such as severe alcoholic hepatitis.
Savio John, M.B., B.S.
Raymond T. Chung, M.D.
Massachusetts General Hospital, Boston, MA
sjohn5@partners.org No potential conflict of interest relevant to this letter was reported.
To the Editor:
Mathurin et al. indicate that liver transplantation is beneficial in severe acute alcoholic hepatitis that is resistant to medical treatment. This benefit on an individual level will inevitably cause problems on a population level in the context of organ shortage, given the high prevalence of alcoholic cirrhosis and the difficulty in predicting alcohol relapse.
We reported the results of a randomized trial in which immediate listing for liver transplantation was compared with standard care in patients with Child–Pugh class B alcoholic cirrhosis.1 Our study did not show a survival benefit associated with immediate listing and stressed the increased risk of extrahepatic cancers. However, we conducted regularly scheduled interviews of patients and their relatives and systematic measures of alcohol concentrations in blood and urine for 5 years, and we evaluated through multivariate analysis the predictors of alcohol relapse. We were surprised to find that transplantation had a protective effect (Table 1Table 1
Time-Dependent Cox Regression Analysis of Factors Associated with Alcohol Relapse in the TRANSCIAL Study.).Liver transplantation could bring about positive psychological changes in patients who are held in greater esteem by society and wish to honor their donor's memory. Decreased alcohol consumption could also be the consequence of psychological interventions or immunosuppressive drugs.
Vincent Di Martino, M.D., Ph.D.
Frances Sheppard, M.P.W.
Claire Vanlemmens, M.D.
Centre Hospitalier Universitaire de Besançon, Besançon, France
vdimartino@chu-besancon.fr No potential conflict of interest relevant to this letter was reported.
1 References1
Vanlemmens C ,Di Martino V ,Milan C , et al. Immediate listing for liver transplantation versus standard care for Child-Pugh stage B alcoholic cirrhosis: a randomized trial. Ann Intern Med 2009;150:153-161
Web of Science | Medline
Author/Editor Response
The letters concerning our recent article raise important issues. Liver transplantation with cadaveric donors for severe alcoholic hepatitis that has not responded to medical management is in itself a complex ethical issue and, like any other indication, needs to be considered in light of the scarcity of donor organs. However, liver transplantation involving living donors raises other important ethical issues. Indeed, in our selection process, the patient's family was actively involved in the decision process. In living-donor liver transplantation, family and team members confront several dilemmas (e.g., the interaction between the selection process and the evaluation of a person's willingness to donate, as well as difficulties in providing objective information on the risk of death for both the recipient and the donor), with the risk of inducing biased selection. Since most deaths occur early in patients who have not undergone transplantation and have not had a response to treatment, the decision to place the patient on the list for liver transplantation and to perform transplantation was made soon after ascertaining the patient's lack of response to treatment, raising the question of feasibility in the context of living-donor liver transplantation. For all these reasons, we do not recommend living-donor liver transplantation for severe alcoholic hepatitis at the present time.
We agree that substantial perioperative mortality is a key issue. Five of six deaths were related to infection occurring within 2 weeks after liver transplantation. Infection is a frequent complication in patients with alcoholic hepatitis, particularly in patients who do not have a response to glucocorticoids, and extensive infection screening is warranted.1 In light of the four deaths related to aspergillosis, strategies evaluating antifungal prophylaxis, early arrest of glucocorticoids, and tailoring of immunosuppressive regimens need to be evaluated. Survival after liver transplantation should improve with experience and with the learning curve of the centers.
Our findings challenge the 6-month abstinence rule in this particular situation. No relapse of alcoholism was observed during the 6 months after liver transplantation, although three patients later had relapses. Given the approximately 25 to 35% alcohol relapse rate over the long term among patients who undergo liver transplantation for alcoholic cirrhosis,2 the rate of relapse in our study seems low and might be related to the stringency of our selection process. As mentioned, liver transplantation could have a protective effect on alcohol relapse. However, this protective effect, observed in patients with Child–Pugh class B alcoholic cirrhosis, cannot be extended to our severely ill highly selected patients with alcoholic hepatitis. Finally, future studies evaluating long-term sobriety and the reproducibility of our selection process are warranted.
Christophe Moreno, M.D., Ph.D.
Erasme Hospital, Brussels, BelgiumJean-Charles Duclos-Vallée, M.D., Ph.D.
Hôpital Paul Brousse, Villejuif, FrancePhilippe Mathurin, M.D., Ph.D.
Hôpital Claude Huriez, Lille, FranceSince publication of their article, the authors report no further potential conflict of interest.
2 References1
Louvet A ,Wartel F ,Castel H , et al. Infection in patients with severe alcoholic hepatitis treated with steroids: early response to therapy is the key factor. Gastroenterology 2009;137:541-548
CrossRef | Web of Science | Medline2
Pageaux GP ,Bismuth M ,Perney P , et al. Alcohol relapse after liver transplantation for alcoholic liver disease: does it matter? J Hepatol 2003;38:629-634
CrossRef | Web of Science | Medline
