Reply

Abstract

We thank Solga et al and Deltenre et al for their interest in ACCELERATE-AH. We offer the following points in reply. Both letters highlight the importance of alcohol use after liver transplantation (LT). Although complete post-LT abstinence is the goal, distinguishing clinically harmful patterns of drinking is essential.1Rice J.P. et al.Liver Transpl. 2013; 19: 1377-1386Crossref PubMed Scopus (112) Google Scholar Although sustained alcohol use after LT was associated with increased risk for post-LT death, slips were not, consistent with other studies.2Lee B.P. et al.Gastroenterology. 2018; 155: 422-430 e421Abstract Full Text Full Text PDF PubMed Scopus (195) Google Scholar Our retrospective data likely underestimate slips; however, these carefully selected LT recipients were followed closely after LT, with alcohol questioning at every visit, and routine biochemical testing with ethylglucuronide or phosphatidylethanol by the majority of ACCELERATE-AH sites. Thus, our ability to capture harmful patterns of drinking was relatively high. We also note, in this regard, the contradictory criticism of Deltenre et al, that our study accentuates “the rate of any relapse.” We do, however, acknowledge that a prospective study with protocoled monitoring is essential to better understand drinking behavior by LT recipients with alcoholic hepatitis (AH). Deltenre et al highlight that liver biopsy was not performed to diagnose AH and that the population may have included patients with acutely decompensated cirrhosis rather than AH. A strength of our study is its reflection of US real-world practice, where liver biopsy is rarely done to diagnose AH. We hypothesize that the reason for only 59% of explants having evidence of histologic steatohepatitis relates to the interval from active drinking to histologic evaluation (at LT) and does not exclude the possibility of AH at initial presentation. Ultimately, although we agree that confirmation of steatohepatitis is important for studies of pharmacotherapies in AH targeting active steatohepatitis, this is tangential to addressing LT for life-threatening alcohol-associated liver disease (ALD). Solga et al assert that our report “overlooks” the 3 ethical principles of utility, justice, and respect for persons. They state that LT for AH may lead to increased morbidity and mortality of patients listed for LT for other conditions with lower Model for End-stage Liver Disease (MELD) scores. Indeed, the ongoing organ shortage makes this likely, but is also true for any new or expanded indication for LT, including the recent changing MELD exception thresholds for hepatocellular carcinoma. In addition, ALD has long been disadvantaged in access for LT, although it accounts for 48% of liver-related deaths in the United States,3Singal A.K. et al.Am J Gastroenterol. 2018; 113: 175-194Crossref PubMed Scopus (364) Google Scholar with higher post-LT survival than most other indications for LT; only 24% of LT recipients in 2016 had ALD.4Kim WR, et al. 2018;18(Suppl 1):172-253.Google Scholar The AH subpopulation has been further marginalized and historically denied any access to LT by mandated sobriety periods that were admittedly arbitrary and with limited scientific validity.5Mathurin P. et al.Curr Opin Organ Transplant. 2018; 23: 175-179PubMed Google Scholar Furthermore, the desire to deny appropriate therapy to patients with life-threatening ALD is part of a more general failure to acknowledge that this is a medical condition, as shown by Dr Solga’s use of the term recidivism to describe relapse. By asserting that it is unethical to provide a life-saving procedure purely based on etiology of disease and preconceived stigma, Solga et al are reviving the discredited theory that patients with alcohol use disorder are less deserving of medical and surgical care, which violates other well-known ethical consensus statements.6Moss A.H. et al.JAMA. 1991; 265: 1295-1298Crossref PubMed Scopus (170) Google Scholar, 7Benjamin M TJ. In: Lucey MR et al (eds). Liver transplantation and the alcoholic patient: medical, surgical and psychosocial issues. Cambridge: Cambridge University Press; 1994.Google Scholar Their concerns about the “liberal expansion” of early LT and ALD patients being “deincentivized” falls just short of fear mongering, while omitting that our study is consistent with previous literature and guidelines in offering early LT to a highly selected population of patients with AH.3Singal A.K. et al.Am J Gastroenterol. 2018; 113: 175-194Crossref PubMed Scopus (364) Google Scholar, 8European Association for the Study of the Liver et al.J Hepatol. 2018; 69: 154-181Abstract Full Text Full Text PDF PubMed Scopus (384) Google Scholar The authors highlight the demographic landscape of our cohort, which was predominantly white, male, and privately insured. Indeed, the majority of the general LT population fit into these categories and whether LT for AH contributes to a disparity should be assessed in the context of an accurate measurement of national AH prevalence. Finally, Solga et al argue that early LT for AH violates respect for persons, citing the severity of illness and acuity of disease. This scenario is no different from patients with acute liver failure, the most common etiology being self-administered acetaminophen overdose, which is a well-accepted indication for LT, and prioritized above all LT candidates by status 1A priority. To deny access to patients with AH with “encephalopathy and imminent threat of life” is contradictory to current well-accepted practice and in direct violation of the federally mandated final rule, which prioritizes those who are sickest and would derive the most benefit from LT. In summary, our study shows that salvage LT for AH is life saving and should be explored as an option for appropriate candidates. How patient selection should be conducted, how this will affect LT candidates with other liver diseases, and how to best prevent and treat alcohol use disorder after LT requires further study and discussion, and we thank the authors for highlighting issues that should frame this ongoing dialogue. Early Liver Transplantation for Alcoholic HepatitisGastroenterologyVol. 156Issue 1PreviewWe read with great interest this month’s issue of Gastroenterology in which Lee et al1 present data from a retrospective cohort of patients with severe alcoholic hepatitis (AH) who have undergone early liver transplantation (LT). The article, reflecting the real-world experience of transplantation in patients with a controversial indication for LT, highlights not only the limitations of studying this disease process in a retrospective fashion but also frames the more provocative debate that must occur with respect to the ethics of organ transplantation in this patient population. Full-Text PDF Outcomes After Early Liver Transplantation for Patients With Severe Alcoholic Hepatitis: Additional Evidence From a Meta-analysisGastroenterologyVol. 156Issue 1PreviewWe read with interest the article from Lee et al1 about early liver transplantation for severe alcoholic hepatitis. We compliment them for their exhaustive collection of data on patients transplanted for alcoholic hepatitis across the United States in the retrospective ACCELARATE-AH study. We would like to add some comments that may contribute to the debate on this hot topic. Full-Text PDF