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Effect of the clinical course of acute-on-chronic liver failure prior to liver transplantation on post-transplant survival.

ABSTRACT: BACKGROUND & AIMS:Patients with acute-on-chronic liver failure (ACLF) can be listed for liver transplantation (LT) because LT is the only curative treatment option. We evaluated whether the clinical course of ACLF, particularly ACLF-3, between the time of listing and LT affects 1-year post-transplant survival. METHODS:We identified patients from the United Network for Organ Sharing database who were transplanted within 28 days of listing and categorized them by ACLF grade at waitlist registration and LT, according to the EASL-CLIF definition. RESULTS:A total of 3,636 patients listed with ACLF-3 underwent LT within 28 days. Among those transplanted, 892 (24.5%) recovered to no ACLF or ACLF grade 1 or 2 (ACLF 0-2) and 2,744 (75.5%) had ACLF-3 at transplantation. One-year survival was 82.0% among those transplanted with ACLF-3 vs. 88.2% among those improving to ACLF 0-2 (p <0.001). Conversely, the survival of patients listed with ACLF 0-2 who progressed to ACLF-3 at LT (n = 2,265) was significantly lower than that of recipients who remained at ACLF 0-2 (n = 17,631) at the time of LT (83.8% vs. 90.2%, p <0.001). Cox modeling demonstrated that recovery from ACLF-3 to ACLF 0-2 at LT was associated with reduced 1-year mortality after transplantation (hazard ratio0.65; 95% CI 0.53-0.78). Improvement in circulatory failure, brain failure, and removal from mechanical ventilation were also associated with reduced post-LT mortality. Among patients >60 years of age, 1-year survival was significantly higher among those who improved from ACLF-3 to ACLF 0-2 than among those who did not. CONCLUSIONS:Improvement from ACLF-3 at listing to ACLF 0-2 at transplantation enhances post-LT survival, particularly in those who recovered from circulatory or brain failure, or were removed from the mechanical ventilator. The beneficial effect of improved ACLF on post-LT survival was also observed among patients >60 years of age. LAY SUMMARY:Liver transplantation (LT) for patients with acute-on-chronic liver failure grade 3 (ACLF-3) significantly improves survival, but 1-year survival probability after LT remains lower than the expected outcomes for transplant centers. Our study reveals that among patients transplanted within 28 days of waitlist registration, improvement of ACLF-3 at listing to a lower grade of ACLF at transplantation significantly enhances post-transplant survival, even among patients aged 60 years or older. Subgroup analysis further demonstrates that improvement in circulatory failure, brain failure, or removal from mechanical ventilation have the strongest impact on post-transplant survival.

SUBMITTER: Sundaram V

PROVIDER: S-EPMC7183313 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Project description:Background & aimsUncertainties 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.MethodsWe 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.ResultsWe 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 <0.001), regardless of organ quality. Creation of 2-way sensitivity analyses, with variation in the probability of receiving an optimal organ and expected post-transplant mortality, indicated that overall survival is maximized by earlier LT, particularly among candidates >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%.ConclusionDuring 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 summaryIn 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.

Project description:Patients with acute liver failure (ALF) have a high risk of death that can be substantially reduced with liver transplantation. It is a challenge to predict which patients with ALF will survive without liver transplant because available prognostic scoring systems are inadequate. We devised a mathematical model, using a large dataset collected by the Acute Liver Failure Study Group, which can predict transplant-free survival in patients with ALF.We performed a retrospective analysis of data from 1974 subjects who met criteria for ALF (coagulopathy and hepatic encephalopathy within 26 weeks of the first symptoms, without pre-existing liver disease) enrolled in the Acute Liver Failure Study Group database from January 1, 1998 through June 11, 2013. We randomly assigned the subjects to development and validation cohorts. Data from the development cohort were analyzed to identify factors associated with transplant-free survival (alive without transplantation by 21 days after admission to the study). Statistically significant variables were used to create a multivariable logistic regression model.Most subjects were women (70%) and white (78%); acetaminophen overdose was the most common cause (48% of subjects). The rate of transplant-free survival was 50%. Admission values of hepatic encephalopathy grade, ALF etiology, vasopressor use, and log transformations of bilirubin and international normalized ratio were significantly associated with transplant-free survival, based on logistic regression analysis. In the validation cohort, the resulting model predicted transplant-free survival with a C statistic value of 0.84, 66.3% accuracy (95% confidence interval, 63.1%-69.4%), 37.1% sensitivity (95% confidence interval, 32.5%-41.8%), and 95.3% specificity (95% confidence interval, 92.9%-97.1%).Using data from the Acute Liver Failure Study Group, we developed a model that predicts transplant-free survival of patients with ALF based on easily identifiable hospital admission data. External validation studies are required.

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Effect of the clinical course of acute-on-chronic liver failure prior to liver transplantation on post-transplant survival.

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