Early transplantation maximizes survival in severe acute-on-chronic liver failure: results of a Markov decision process model

Abstract Background 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 timing of LT among patients with ACLF-3 within 7 days of listing, to maximize overall one-year survival probability. Results We analyzed six 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 versus remaining on the waiting list for even 1 additional day (p 60 years or with 4-6 organ failures. 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 three variables. Lay summary In the setting of grade three 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 versus waiting 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.