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Attitudes toward liver transplantation for ACLF-3 determine equity of access

Published:November 05, 2022DOI:https://doi.org/10.1016/j.jhep.2022.10.029

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      • ‘Equity’ and ‘Justice’ for patients with acute-on chronic liver failure: A call to action
        Journal of HepatologyVol. 75Issue 5
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          Acute-on-chronic liver failure (ACLF) occurs in hospitalised patients with cirrhosis and is characterised by multiorgan failures and high rates of short-term mortality. Without liver transplantation (LT), the 28-day mortality rate of patients with ACLF ranges from 18–25% in those with ACLF grade 1 to 68–89% in those with ACLF grade 3. It has become clear that patients with ACLF do not have equitable access to LT because of current allocation policies, which are based on prognostic scores that underestimate their risk of death and a lack of appreciation of the clear evidence of transplant benefit in carefully selected patients (who can have excellent post-LT outcomes).
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      To the Editor:
      Liver transplantation (LT) is currently the most effective treatment available for critically ill individuals with cirrhosis and multiple organ failure, provided they are carefully selected.
      • Abdallah M.A.
      • Waleed M.
      • Bell M.G.
      • Nelson M.
      • Wong R.
      • Sundaram V.
      • et al.
      Systematic review with meta-analysis: liver transplant provides survival benefit in patients with acute on chronic liver failure.
      While support for LT for those with grade 3 acute-on-chronic liver failure (ACLF-3) is theoretically increasing within the transplant community, in practice, utilization of LT for these patients remains debated and problematic. For example, studies of the French transplant registry
      • Artzner T.
      • Legeai C.
      • Antoine C.
      • Jasseron C.
      • Michard B.
      • Faitot F.
      • et al.
      Liver transplantation for critically ill cirrhotic patients: results from the French transplant registry.
      and of a European cohort
      • Belli L.S.
      • Duvoux C.
      • Artzner T.
      • Bernal W.
      • Conti S.
      • Cortesi P.A.
      • et al.
      Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: results of the ELITA/EF-CLIF collaborative study (ECLIS).
      ,
      • Artzner T.
      • Bernal W.
      • Belli L.S.
      • Conti S.
      • Cortesi P.A.
      • Sacleux S.-C.
      • et al.
      Location and allocation: inequity of access to liver transplantation for patients with severe acute-on-chronic liver failure in Europe.
      of critically ill individuals with cirrhosis have shown that access to LT varies significantly across countries and across individual transplant centers, leading to inequities in access to this life-saving treatment. We are therefore still far from equity and justice in this area of transplant medicine. Several potential obstacles may hinder access to LT for patients with ACLF-3: admission to the intensive care unit (ICU), referral to a tertiary center, inclusion in the waiting list, timely organ allocation and, most importantly, an agreement between the members of the transplant team on the value of LT in this indication. Access to LT and optimal care for this specific group of potential transplant candidates requires a comprehensive, multidisciplinary approach. Transplant hepatologists, surgeons, anesthesiologists and intensivists, both within transplant centers but also in primary and secondary centers, need to be aware and convinced that LT is a potential treatment for a critically ill individual with cirrhosis.
      This survey was designed through discussion between experts of EF-CLIF and ELITA and an online questionnaire was sent to the participants of the CHANCE trial.
      European Foundation for Study of Chronic Liver Failure
      Liver transplantation in patients with CirrHosis and severe acute-on-chronic liver failure (ACLF): iNdications and outComEs [Internet]. clinicaltrials.gov.
      Multiple choice questions were targeted at describing LT practices, identifying obstacles to LT for individuals with ACLF-3 and determining potential solutions to overcome these obstacles. Questionnaires were sent to 1,031 transplant doctors and the first 100 responses were analyzed. All data were collected anonymously.
      The 100 participants who completed the survey came from 26 different countries. Of these, 76 identified themselves as hepatologists, 13 as intensivists and/or anesthesiologists and 11 as surgeons. Most respondents (58%) came from transplant centers that performed more than 50 LTs yearly. While fewer than 5 individuals with ACLF-3 were transplanted annually in the majority of the respondents’ centers (65%), most respondents (70%) claimed that their centers could transplant more than 5 every year.
      The majority (66%) agreed that there was enough evidence in the literature to support transplanting those with ACLF-3. Despite such evidence, 70% declared that individuals with ACLF-3 did not have adequate access to LT in their region (Fig. 1A,B). When asked whether patients with ACLF-3 did not have sufficient access to the ICU in their region, on a scale of 1 (“do not agree at all”) to 5 (“strongly agree”), 50 responses were between 4 and 5. When asked the same question, but this time in their own center, only 21 responses were between 4 and 5 (Fig. 1C,D).
      Figure thumbnail gr1
      Fig. 1Selected responses to the ACLF liver transplant questionnaire.
      ACLF, acute-on-chronic liver failure; ICU, intensive care unit.
      While 27 respondents noted that colleagues in their own transplant centers were reluctant to put critically ill individuals with cirrhosis on the transplant waiting list, this was reported more frequently (59 respondents) by physicians who referred patients to LT centers but did not directly work in them (Fig. 1E,F). When respondents were asked to identify the group(s) of physicians that was/were most unwilling to consider LT for individuals with ACLF-3 in their center, anesthesiologists came first (40 respondents), followed by intensivists (38 respondents), surgeons (32 respondents) and hepatologists (21 respondents). There was a significant split over the issue of prioritizing access to LT for individuals with ACLF-3, with 48 respondents declaring that the average waiting time for those with ACLF-3 was too long in their center. When asked whether the allocation system in their region/country did not prioritize those with ACLF-3 sufficiently, 53 respondents agreed. Finally, 82 respondents were in favor of adding mechanisms to organ allocation algorithms in order to exclude critically ill patients if they are too sick at the time of organ proposal.
      In summary, this survey reveals a discrepancy between clinical evidence and actual practice concerning access to LT for individuals with ACLF-3. It illustrates the growing view that the use of LT should be expanded for individuals with ACLF-3, while highlighting some of the key obstacles that need to be overcome to achieve this aim. From an institutional perspective, organ allocation algorithms need to be tailored according to regional and national determinants to enable adequate prioritization of those with ACLF-3, while ensuring that patients who are too sick to be transplanted can be identified. From a clinical perspective, it is fundamental to convince colleagues in transplant centers, but also outside transplant centers, that those with ACLF-3 should be considered for ICU admission, referral to a tertiary LT center and pre-transplant work-up for potential listing.
      Expanding the use of LT for those with ACLF-3 is a medical undertaking different in nature and broader in scope than increasing access to a particular drug, intensive care support or surgical technique. It requires widespread discussion, education and further research, which will change the way the medical community thinks about managing critically ill individuals with cirrhosis.

      Financial support

      The authors received no financial support to produce this manuscript.

      Conflicts of interest

      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 Discovery, a spin out company from University College London, Hepyx Limited and Cyberliver. He had research collaborations with Yaqrit Discovery. The other authors have no conflicts of interest to declare.
      Please refer to the accompanying ICMJE disclosure forms for further details.

      Authors’ contributions

      All authors contributed equally to this work. Concept: TA, LB, FF, RJ. Writing: TA, LB, FF, RJ. Revision for important intellectual content and final approval of the version to be published: TA, LB, FF, RJ.

      Supplementary data

      The following are the supplementary data to this article:

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