Model to Calculate Harms and Benefits of Early vs Delayed Liver Transplantation for Patients With Alcohol-Associated Hepatitis

Abstract

This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e17 (https://www. gastrojournal.org/cme/home). Learning Objective: Upon completion of this CME activity, successful learners will be able to state the expected short-and long-term outcomes of a patient with severe, medically refractory, acute alcohol-associated hepatitis presented with 2 different transplant eligibility policies: early (ie, without minimum period of sobriety) versus delayed (eg, 6-month wait) liver transplantation. BACKGROUND & AIMS: Early liver transplantation (without requiring a minimum period of sobriety) for severe alcoholassociated hepatitis (AH) is controversial: many centers delay eligibility until a specific period of sobriety (such as 6 months) has been achieved. To inform ongoing debate and policy, we modeled long-term outcomes of early vs delayed liver transplantation for patients with AH. METHODS: We developed a mathematical model to simulate early vs delayed liver transplantation for patients with severe AH and different amounts of alcohol use after transplantation: abstinence, slip (alcohol use followed by sobriety), or sustained use. Mortality of patients before transplantation was determined by joint-effect model (based on Model for End-Stage Liver Disease [MELD] and Lille scores). We estimated life expectancies of patients receiving early vs delayed transplantation (6-month wait before placement on the waitlist) and life years lost attributable to alcohol use after receiving the liver transplant. RESULTS: Patients offered early liver transplantation were estimated to have an average life expectancy of 6.55 life years, compared with an average life expectancy of 1.46 life years for patients offered delayed liver transplantation (4.49-fold increase). The net increase in life expectancy from offering early transplantation was highest for patients with Lille scores of 0.50-0.82 and MELD scores of 32 or more. Patients who were offered early transplantation and had no alcohol use afterward were predicted to survive 10.85 years compared with 3.62 years for patients with sustained alcohol use after transplantation (7.23 life years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores. CONCLUSIONS: In a modeling study of assumed carefully selected patients with AH, early vs delayed liver transplantation (6 months of abstinence from alcohol before transplantation) increased survival times of patients, regardless of estimated risk of sustained alcohol use after transplantation. These findings support early liver transplantation for patients with severe AH. The net increase in life expectancy was maintained in all simulated extreme scenarios but should be confirmed in prospective studies. Sustained alcohol use after transplantation significantly reduced but did not eliminate the benefits of early transplantation. Strategies are needed to prevent and treat posttransplanta...

Alcoholic hepatitis: Towards an era of personalised management

“…Due to the fact that a randomised controlled trial may be a questionable study design for demonstrating the benefits of early liver transplantation in patients with severe AH, Lee et al have performed a modelling approach that tests immediate transplantation versus a delayed procedure. 41 In this study, early transplantation was associated with improved survival, despite the negative impact of alcohol relapse on outcomes. However, this strategy needs to be confirmed in prospective studies.…”

Early Liver Transplantation in Acute Alcoholic Hepatitis

“…Lee et al found early liver transplantation provided a survival benefit for candidates with severe AAH, regardless of risk of posttransplant alcohol use, but the survival benefit of liver transplantation was reduced with post-transplant alcohol use. 16 These studies in the United States and Europe provide evidence supporting the role of early liver transplantation for severe AAH and for reevaluation of the 6-month rule.…”

“…6 months of abstinence) liver transplantation among patients with severe AAH and varying degrees of alcohol use posttransplant. 16 This study quantified the survival benefit of early liver transplantation and the number of life-years lost after liver transplant due to resumed alcohol use. Lee et al found early liver transplantation provided a survival benefit for candidates with severe AAH, regardless of risk of posttransplant alcohol use, but the survival benefit of liver transplantation was reduced with post-transplant alcohol use.…”

Increase in Alcoholic Hepatitis as an Etiology for Liver Transplantation in the United States: A 2004–2018 Analysis

“…A central issue is identifying when LT is justified in patients with AH. A recent study reported a notable survival benefit with early LT for AH in comparison to late LT. 10 Such data are of utmost importance and may continue to shift the attitude toward early LT for AH patients. In our analysis, we noticed that the median time from registration on the OPTN waiting list to receiving an LT decreased dramatically from 58 days in the 2004–2009 period to 5 days in the 2014–2018 period (Table S3, SDC, http://links.lww.com/TXD/A286 ).…”