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CON: Liver Transplant Should Not Be Performed in Patients With Acute Alcoholic Hepatitis

2020; Lippincott Williams & Wilkins; Volume: 16; Issue: 5 Linguagem: Inglês

10.1002/cld.937

2046-2484

Parita Patel, Jennifer Wang, Anjana Pillai,

Substance Abuse Treatment and Outcomes

Watch a video presentation of this article Early liver transplantation (LT) as a treatment for severe AH has remained a controversial topic. Since the publication of a seminal European pilot study demonstrating the effectiveness of LT as a rescue option for patients with severe AH who were not responding to medical therapy,1 there has been a paradigm shift leading to a wider adoption of early LT for AH in the United States. A UNOS-based study demonstrated a 4-fold increase in the listing of AH for transplantation from 2011 to 2016.2 In an era of persistent organ shortage, it is crucial that we focus on an effective treatment strategy for AUD, develop objective selection criteria, and await results of prospective studies on long-term outcomes before liberating LT indications to include AH. Alcohol dependence is a chronic medical illness with a relapsing and remitting course that is not treated by LT. This is exemplified in the four pivotal trials that evaluated LT for patients with AH.1, 3-5 Selection criteria varied from study to study but remained stringent, because only 2% to 8% of patients evaluated were selected for participation. Despite these strict selection criteria, most trials had a relapse rate of 11% to 25% in their transplanted cohort. These high rates of alcohol use posttransplant were also demonstrated in a prospective study performed by DiMartini et al.6 In this study, 46% of patients with alcoholic liver disease reported alcohol use posttransplant, with 22% of patients drinking during the first year posttransplant. These high rates of alcohol use matter because they have been repeatedly linked to high rates of mortality. In a retrospective study of 147 posttransplant patients with severe AH, the only factor associated with increased overall mortality was alcohol use after LT.5 In fact, any alcohol use after LT was associated with a 3.5 times greater risk for death when compared with patients who abstained from alcohol5 (Fig. 1). Although transplant may not treat alcohol dependence, substance abuse rehabilitation has been shown to be a beneficial treatment. In a study by Rodrigue et al.,7 patients who received substance abuse treatment both before and after transplantation had significantly lower rates of alcohol relapse (16%) when compared with patients who received substance abuse treatment only before transplant (45%) or no substance abuse treatment (41%) (P = 0.03) (Fig. 2). Despite these striking data, few transplant centers have established substance abuse treatment plans or programs once transplantation is performed. Oftentimes, centers do not have the financial means or resources to institute such programs, leaving alcohol use untreated posttransplant, and ultimately placing patients at risk for death. Therefore, given a lack of posttransplant substance abuse treatment programs, it is premature to adopt a policy to transplant these patients without a plan for treating the ultimate issue at hand. This high alcohol relapse rate posttransplantation demands objective pre-LT tools to identify those at high or low risk for sustained or harmful alcohol use after LT. Over the past decade, several prognostic tools have been proposed to assess the risk for alcohol relapse.8-11 However, none of these have been externally validated in clinical practice or research studies for patients with alcoholic liver disease. This is a key component of candidate selection criteria, and the lack of a widely accepted prognostic tool for optimal selection in LT for AH is contributing to variations in center selection protocols. The study by Mathurin and colleagues used stringent selection criteria, resulting in less than 2% of all patients admitted with AH to be selected for the trial.1 In fact, a pilot study in the United Kingdom failed to recruit any patients over a 3-year period, presumably because of extremely stringent selection criteria.12 The studies in the United States expanded on Mathurin and colleagues’ selection criteria and were able to recruit more patients. These criteria included patients with recent gastrointestinal bleeding, infection, past failed attempts at alcohol rehabilitation, psychiatric disease, illicit drug use, and even patients with high-risk alcoholism relapse scores.1, 3, 4 The lack of standardization in candidate selection allows for liberal expanded criteria that might inadvertently drive transplant centers to “set the bar low” to get more patients listed, especially in regions with multiple competing transplant centers. Furthermore, variation in policy can allow patients to self-refer to centers that follow less stringent guidelines and create further disparities in access to LT. Another major consideration is the potential deleterious effect of negative public perception on organ donation rate. Proponents of LT for AH often cite a public opinion survey demonstrating a majority of respondents were at least neutral about the idea. However, the same survey also showed that 30% of the participants indicated hesitation to donate their organs.13 In an already small donor pool, this is the 30% we cannot afford to lose. Highly publicized cases, such as George Best and Mickey Mantle, should also serve as warnings for the downstream effects of a public relapse. Shortly after recovery from his LT, George Best returned to drinking and ultimately died 3 years later. In one year, liver donation in the United Kingdom dropped by 25%. The decline in donors was blamed on the “George Best effect.”14 In the era of social media, negative publicity could be detrimental not only at a center level but also to the transplant community at large because of public mistrust. Given the lack of predictive tools and objective protocols, we are simply not ready for broad application of transplantation to all patients with acute AH at this time. With scarcity of organs being a concern, we must take every effort to find treatment for AUD with the goal of preventing liver disease altogether. Prior to adopting a universal policy, we need to continue to pursue the optimal selection criteria for patients with AH undergoing transplant and identify a subset of patients who are at low risk for relapse. In addition, it will be just as essential to establish well-validated standardized criteria to identify low-risk patients for LT. Without the resources in place to evaluate and treat patients with liver disease and AUD, we cannot justify transplantation to all patients with acute AH at this time.