Reply to: “Liver transplantation and severe acute alcoholic hepatitis: An ethical consideration”
Authors: Vincent Donckier, Valerio Lucidi, Thierry Gustot, Christophe Moreno
Journal: Journal of Hepatology (2014)

Liver transplantation and severe acute alcoholic hepatitis: An ethical considerationJournal of HepatologyVol. 61Issue 3PreviewWe have read the excellent paper by Donckier et al. [1]. The authors conclude that there are no major ethical barriers in transplanting patients affected by severe alcoholic hepatitis (SAH), non-responder to medical therapy. We totally agree with this statement [2]. Full-Text PDF Open AccessEthical considerations regarding early liver transplantation in patients with severe alcoholic hepatitis not responding to medical therapyJournal of HepatologyVol. 60Issue 4PreviewA recent study proposed that liver transplantation may represent life-saving treatment in patients with severe alcoholic hepatitis not responding to medical therapy. In this pilot experience, stringent patient selection resulted in major improvement of short-term survival with low rates of post-transplant alcohol relapse. In the context of organ shortage, which imposes a need for strict selection of transplant candidates, these results raise major ethical questions. Reluctance to perform liver transplantation in alcoholics is based on the fact that alcoholism is frequently considered to be self-inflicted and on fears of harmful post-transplant alcoholism recurrence. Full-Text PDF Open Access We thank Gianni Testino and Paolo Borro for their comments on our paper [[1]Donckier V. Lucidi V. Gustot T. Moreno C. Ethical considerations early liver transplantation in patients with severe alcoholic hepatitis not responding to medical therapy.J Hepatol. 2014; 60: 866-871Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar].As they first pointed, we agree that there are evident paradoxes in the attitude of our societies toward alcohol consumption. On the one hand, alcohol drinking is largely encouraged, namely by advertising campaigns, and moderate or “controlled” drinking remains a mark of social integration. On the other hand, addictive drinking still leads to global moral disapproval and social exclusion, alcoholic patients being considered as responsible for their disease. Testino and Borro also underlined that global judgment of the alcoholism based on the severity of the liver disease could lead to unfair patient categorization as similar alcohol consumptions could lead to very different outcomes in different individuals, according to genetic backgrounds [[2]Trépo E. Gustot T. Degré D. Lemmers A. Verset L. Demetter P. et al.Common polymorphism in the PNPLA3/adiponutrin gene confers higher risk of cirrhosis and liver damage in alcoholic liver disease.J Hepatol. 2011; 55: 906-912Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar] and/or other risk factors.As the authors stated, we also consider that moral and societal appreciations strongly influence the entire debate about liver transplantation (LT) in alcoholic liver diseases and particularly in patients with severe alcoholic hepatitis (SAH). Of course, the discussion about LT in these patients is dramatically exacerbated in the current context of organ shortage. On ethical grounds however, we would like to suggest that the transplant community has the duty to regularly evaluate and re-evaluate the rules for organ allocation, aiming at ensuring the optimal use of a scarce therapeutic resource. The definition of the optimal graft use in this context remains debatable but, based on fundamental ethical principles, we propose that the primary aim of organ transplantation should be a life-saving procedure, in the absence of any other therapeutic alternative, leading to satisfactory long-term results such as long-term graft and patient survivals. Optimally, decisional algorithms should be based on objective and transparent data, independently from any moral, societal or cultural influences. In parallel, the indications for LT should not be considered as definitively established, and, we could expect that in the next years, better disease understanding and therapeutic advances in alcohol liver diseases but also in other conditions, such as in hepatitis C or in hepatocellular carcinoma, will significantly modify the listing strategies, both to restrict or to enlarge the inclusion criteria.At this stage, of course, early LT in patients with SAH remains a challenging procedure. A first step has been made with an initial report showing satisfactory results in highly selected patients [[3]Mathurin P. Moreno C. Samuel D. Dumortier J. Salleron J. Durand F. et al.Early liver transplantation for severe alcoholic hepatitis.N Engl J Med. 2011; 365: 1790-1800Crossref PubMed Scopus (595) Google Scholar]. Yet, these first results have now to be confirmed in strict investigational frameworks, with longer follow-up and in larger patient population. In this process, the definition of accurate selection criteria has a critical importance. In that sense, it should be mentioned that a multicentre prospective study has been initiated, to identify and to validate various selection criteria [[4]http://clinicaltrials.gov/show/NCT01756794.Google Scholar]. Among these factors, we fully agree with Testino and Borro that familial and socio-professional environments, attendance to self-help groups and cooperation with alcohol units play a pivotal role.We are convinced that a door has now been opened to propose LT in selected patients with SAH. Careful evaluation of the selection criteria and analysis of the long-term results, including overall survivals, analysis of alcohol relapses, eventually leading to subsequent graft damages, will constitute the next steps to fully validate this procedure.Conflict of interestThe authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. We thank Gianni Testino and Paolo Borro for their comments on our paper [[1]Donckier V. Lucidi V. Gustot T. Moreno C. Ethical considerations early liver transplantation in patients with severe alcoholic hepatitis not responding to medical therapy.J Hepatol. 2014; 60: 866-871Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar]. As they first pointed, we agree that there are evident paradoxes in the attitude of our societies toward alcohol consumption. On the one hand, alcohol drinking is largely encouraged, namely by advertising campaigns, and moderate or “controlled” drinking remains a mark of social integration. On the other hand, addictive drinking still leads to global moral disapproval and social exclusion, alcoholic patients being considered as responsible for their disease. Testino and Borro also underlined that global judgment of the alcoholism based on the severity of the liver disease could lead to unfair patient categorization as similar alcohol consumptions could lead to very different outcomes in different individuals, according to genetic backgrounds [[2]Trépo E. Gustot T. Degré D. Lemmers A. Verset L. Demetter P. et al.Common polymorphism in the PNPLA3/adiponutrin gene confers higher risk of cirrhosis and liver damage in alcoholic liver disease.J Hepatol. 2011; 55: 906-912Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar] and/or other risk factors. As the authors stated, we also consider that moral and societal appreciations strongly influence the entire debate about liver transplantation (LT) in alcoholic liver diseases and particularly in patients with severe alcoholic hepatitis (SAH). Of course, the discussion about LT in these patients is dramatically exacerbated in the current context of organ shortage. On ethical grounds however, we would like to suggest that the transplant community has the duty to regularly evaluate and re-evaluate the rules for organ allocation, aiming at ensuring the optimal use of a scarce therapeutic resource. The definition of the optimal graft use in this context remains debatable but, based on fundamental ethical principles, we propose that the primary aim of organ transplantation should be a life-saving procedure, in the absence of any other therapeutic alternative, leading to satisfactory long-term results such as long-term graft and patient survivals. Optimally, decisional algorithms should be based on objective and transparent data, independently from any moral, societal or cultural influences. In parallel, the indications for LT should not be considered as definitively established, and, we could expect that in the next years, better disease understanding and therapeutic advances in alcohol liver diseases but also in other conditions, such as in hepatitis C or in hepatocellular carcinoma, will significantly modify the listing strategies, both to restrict or to enlarge the inclusion criteria. At this stage, of course, early LT in patients with SAH remains a challenging procedure. A first step has been made with an initial report showing satisfactory results in highly selected patients [[3]Mathurin P. Moreno C. Samuel D. Dumortier J. Salleron J. Durand F. et al.Early liver transplantation for severe alcoholic hepatitis.N Engl J Med. 2011; 365: 1790-1800Crossref PubMed Scopus (595) Google Scholar]. Yet, these first results have now to be confirmed in strict investigational frameworks, with longer follow-up and in larger patient population. In this process, the definition of accurate selection criteria has a critical importance. In that sense, it should be mentioned that a multicentre prospective study has been initiated, to identify and to validate various selection criteria [[4]http://clinicaltrials.gov/show/NCT01756794.Google Scholar]. Among these factors, we fully agree with Testino and Borro that familial and socio-professional environments, attendance to self-help groups and cooperation with alcohol units play a pivotal role. We are convinced that a door has now been opened to propose LT in selected patients with SAH. Careful evaluation of the selection criteria and analysis of the long-term results, including overall survivals, analysis of alcohol relapses, eventually leading to subsequent graft damages, will constitute the next steps to fully validate this procedure. Conflict of interestThe authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.