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.

Keywords: DRI; MELD-Na score; Organ failure; UNOS database.

Conflict of interest statement

Conflict of interest

Rajiv Jalan has research collaborations with Yaqrit and Takeda. Rajiv Jalan is the inventor of OPA, which has been patented by UCL and licensed to Mallinckrodt Pharma. He is also the founder of Yaqrit limited, a spin out company from University College London. The other authors have nothing to disclose regarding conflicts of interest relevant to this manuscript.

Please refer to the accompanying ICMJE disclosure forms for further details.

Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1.. One-year post-transplant survival of patients with ACLF 0–2 or ACLF-3 at listing and LT.

*p value comparing survival probability with that of patients with ACLF-3 at listing and ACLF 0–2 at LT. ACLF, acute-on-chronic liver failure; LT, liver transplantation. Survival probability tested using Kaplan-Meier methods with log-rank testing.

Fig. 2.. One-year post-transplant survival of patients with ACLF-3 at listing, categorized by age and ACLF grade at transplantation (p <0.001).

ACLF, acute-on-chronic liver failure.

Fig. 3.. One-year post-transplant survival of patients with ACLF-3 at listing, categorized by timing of transplantation and ACLF grade at transplantation.

ACLF, acute-on-chronic liver failure.