Background & Aims Uncertainties exist surrounding the timing of liver transplantation (LT) among patients with acute-on-chronic liver failure grade 3 (ACLF-3), regarding whether to accept a marginal quality donor organ to allow for earlier LT or wait for either an optimal organ offer or improvement in the number of organ failures, in order to increase post-LT survival. Methods We created a Markov decision process model to determine the optimal timing of LT among patients with ACLF-3 within 7 days of listing, to maximize overall 1-year survival probability. Results We analyzed 6 groups of candidates with ACLF-3: patients age ≤60 or >60 years, patients with 3 organ failures alone or 4-6 organ failures, and hepatic or extrahepatic ACLF-3. Among all groups, LT yielded significantly greater overall survival probability vs. remaining on the waiting list for even 1 additional day (p 60 years old or with 4-6 organ failures. The probability of improvement from ACLF-3 to ACLF-2 does not influence these recommendations, as the likelihood of organ recovery was less than 10%. Conclusion During the first week after listing for patients with ACLF-3, earlier LT in general is favored over waiting for an optimal quality donor organ or for recovery of organ failures, with the understanding that the analysis is limited to consideration of only these 3 variables. Lay summary In the setting of grade 3 acute-on-chronic liver failure (ACLF-3), questions remain regarding the timing of transplantation in terms of whether to proceed with liver transplantation with a marginal donor organ or to wait for an optimal liver, and whether to transplant a patient with ACLF-3 or wait until improvement to ACLF-2. In this study, we used a Markov decision process model to demonstrate that earlier transplantation of patients listed with ACLF-3 maximizes overall survival, as opposed to waiting for an optimal donor organ or for improvement in the number of organ failures.

Highlights • We created a Markov decision process model to maximize overall survival ACLF-3 patients within 7 days of listing. • We examined three variables: earlier transplantation, organ quality, and recovery of organ failures. • Earlier transplantation maximizes overall survival probability, due to high waitlist mortality of patients with ACLF-3. • The impact of a marginal organ on post-LT mortality is less consequential than the mortality from delaying transplantation. • The likelihood of organ failure recovery within 7 days of listing was less than 10%.

Graphical abstract