Early Liver Transplantation for Severe Alcohol-Associated Hepatitis and a History of Prior Liver Decompensation

Abstract

INTRODUCTION:In the published studies of early liver transplantation (LT) for alcohol-associated hepatitis (AH), patients with a prior liver decompensation are excluded. The appropriateness of this criteria is unknown.Methods:Among 6 American Consortium of Early Liver Transplantation for Alcohol-Associated Hepatitis sites, we included consecutive early LT for clinically diagnosed AH between 2007 and 2020. Patients were stratified as first vs prior history of liver decompensation, with the latter defined as a diagnosis of ascites, hepatic encephalopathy, variceal bleeding, or jaundice, and evidence of alcohol use after this event. Adjusted Cox regression assessed the association of first (vs prior) decompensation with post-LT mortality and harmful (i.e., any binge and/or frequent) alcohol use.Results:A total of 241 LT recipients (210 first vs 31 prior decompensation) were included: median age 43 vs 38 years (P = 0.23), Model for End-Stage Liver Disease Sodium score of 39 vs 39 (P = 0.98), and follow-up after LT 2.3 vs 1.7 years (P = 0.08). Unadjusted 1- and 3-year survival among first vs prior decompensation was 93% (95% confidence interval [CI] 89%–96%) vs 86% (95% CI 66%–94%) and 85% (95% CI 79%–90%) vs 78% (95% CI 57%–89%). Prior (vs first) decompensation was associated with higher adjusted post-LT mortality (adjusted hazard ratio 2.72, 95% CI 1.61–4.59) and harmful alcohol use (adjusted hazard ratio 1.77, 95% CI 1.07–2.94).DISCUSSION:Prior liver decompensation was associated with higher risk of post-LT mortality and harmful alcohol use. These results are a preliminary safety signal and validate first decompensation as a criterion for consideration in early LT for AH patients. However, the high 3-year survival suggests a survival benefit for early LT and the need for larger studies to refine this criterion. These results suggest that prior liver decompensation is a risk factor, but not an absolute contraindication to early LT.

Multicentered study of patient outcomes after declined for early liver transplantation in severe alcohol-associated hepatitis

“…Because most patients with AH declined for early LT are declined for psychosocial contraindications and are typically considered “high-risk” patients, this may raise underlying concerns for repeat LT evaluation. However, we do recently show that carefully selected patients with AH with a prior liver decompensating episode, considered unacceptably “high risk” in many centers, have post-LT 1 and 3-year survival of 86% and 78%, respectively, conferring a survival benefit even in these high-risk patients 20. Future studies should focus on further refining psychosocial risk stratification, and who could benefit from repeat LT evaluation in those who have persistent liver decompensation and are able to maintain sobriety.…”

“…However, we do recently show that carefully selected patients with AH with a prior liver decompensating episode, considered unacceptably "high risk" in many centers, have post-LT 1 and 3-year survival of 86% and 78%, respectively, conferring a survival benefit even in these high-risk patients. [20] Future studies should focus on further refining psychosocial risk stratification, and who could benefit from repeat LT evaluation in those who have persistent liver decompensation and are able to maintain sobriety. Nonetheless, we anticipate future LT in patients declined during initial LT evaluation to be rare, and given that probability of 6-month mortality was 51% in our cohort, palliative care/hospice referral may be appropriate for patients with severe AH evaluated, but declined for early LT.…”

ACG Clinical Guideline: Alcohol-Associated Liver Disease

“…Although length of abstinence predicts alcohol use after LT, other factors such as untreated psychiatric disease, history of polysubstance abuse, history of legal consequences related to alcohol use, lack of insight, lack of willingness to engage in AUD treatment, multiple prior failed rehabilitation attempts, and lack of social support are stronger variables associated with recurrent alcohol use after LT (261). Furthermore, a recent study showed 3-year patient survival rates after LT to be lower in those with a history of decompensation vs first episode (72% vs 83%, P = 0.01) (262).…”

Liver transplantation for alcohol-associated hepatitis

“…Since 1995, multiple studies have investigated early liver transplantation as a treatment for severe alcohol-associated hepatitis refractory to medical management (Table 1) [15,24–36,37 ▪ –39 ▪ ,40 ▪▪ –42 ▪▪ ]. In 2011, a landmark French-Belgian prospective study by Mathurin et al compared patients with severe alcohol-associated hepatitis nonresponsive to medical therapy who underwent liver transplantation with nontransplanted matched controls, demonstrating superior survival in patients who were transplanted compared with those who were not (77 vs. 23%, P < 0.001) with only 3 of 26 patients returning to alcohol at 720–1140 days postliver transplantation [29].…”

“…Importantly, though sustained alcohol use postliver transplantation was infrequent, it was also associated with increased mortality [34]. Subsequent ACCELERATE-AH studies have highlighted the improved survival achieved with early vs. delayed transplantation for alcohol-associated hepatitis (6.55 vs. 1.46 life-years, respectively), the superior outcomes in patients transplanted with their first vs. prior hepatic decompensation (93 vs. 86% at 1 year and 85 vs. 78% at 3 years, respectively), and have defined four distinct patterns of postliver transplantation alcohol use: abstinence, late nonheavy drinking, early nonheavy drinking, and early heavy drinking, where substantially worse survival was observed with early relapse (53–63 vs. 95–100% for abstinent/late relapse; P < 0.001) [35,41 ▪▪ ,42 ▪▪ ].…”