Early Allograft Failure Simplified Estimation (EASE) in Liver Transplantation
Condition: Liver Transplant Failure
Study type: Observational

Summary: 
      A variety of clinical scores have been developed with the intent to predict early allograft
      failure after liver transplantation. With the present study the investigators aim to validate
      the recently published L-GrAFT Score on a multicenter cohort from 14 liver transplant centers
      in Italy.

      Secondly, after identifying coefficients which are peculiar for the Italian transplant
      population, the investigators aim to develop a novel, simplified model for the estimation of
      early allograft failure (EASE Score).

      Thirdly, the investigators plan to validate the EASE Score on a population from two liver
      transplant centers in the United Kingdom.
    

Detailed description: 
      Liver transplantation (LT) is the gold standard treatment for end-stage liver disease. The
      broadening of indications has caused a growing gap between patients on the waiting list and
      those who receive a transplant with the consequence of patients still dying while awaiting to
      be transplanted.

      This phenomenon has led the transplant community to expand the donors pool, thus including
      organs with a higher risk profile. The so called marginal organs carry a higher risk of
      failure especially in the early post-transplant phase. Early allograft failure (EAF) is known
      as a poor prognostic factor for patient survival.Treatment of graft failure is based on
      re-transplantation (Re-LT).

      However, there are no clear-cut clinical/biochemical parameters to base the decision of Re-LT
      on. In addition, to which extent EAF is irreversible is not entirely predictable. Such
      prediction has been the objective of extensive research and debate as it can guide the
      physicians through the decision whether or not re-transplanting a recipient of a failing
      graft.

      The availability of an easy algorithm to quickly identify the cases who are irreversibly
      heading towards graft failure and need re-LT is highly desirable.

      Various definitions of EAF have been introduced but they all share the same limitation of
      being based on a dichotomous evaluation of biochemical parameters (e.g. AST, INR, bilirubin,
      etc. below or above a certain cut-off level).

      Recently, a new score has been developed with the aim of overcoming this limitation: the
      Liver Graft Assessment Following Transplantation (L-GrAFT). This score not only provides a
      tool to diagnose EAF but also assesses the severity and the evolution of EAF using the
      kinetics of a set of biochemical parameters. However, L-GrAFT is predictive of EAF at 90
      days, is based on 31 biochemical determinations and has not been validated in a multicenter
      setting.

      With the present study the investigators aim:

        1. to evaluate the performance of the L-GrAFT score and its ability to predict graft loss
           in the early post-operative phase (i.e. 90 days after LT) in a cohort of patients who
           received a primary LT from 2016 to 2017 in one of 14 LT Centers based in Italy,
           analyzing their prospectively maintained databases with a minimum follow up of 6 months;

        2. to develop a simplified algorithm, derived from the L-GrAFT algorithm, based on the
           Italian LT population, reducing the number of determinations allowing an easier data
           entry, which is predictive of EAF at 90 (90dEASE Score) and also at 30 days post LT
           (30dEASE Score);

        3. to validate the EASE scores on a population internal to the Italian database, using
           bootstrap methodology;

        4. to validate the EASE scores on an external UK liver transplant Cohort. The investigators
           are planning to present the results of the study in international congresses and
           meetings and after that to produce a manuscript.
    

Intervention name(s): Liver transplantation
Intervention type(s): Procedure
Intervention description(s): Liver transplantation from deceased donors
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        A total of 1800 recipients of a primary liver transplant (LT) from 14 LT Centers from Italy
        (Training set) and 550 recipients of LT from 2 LT Centers from the United Kingdom
        (Validation set).
      
Keywords: liver transplant; allograft failure; primary dysfunction; early outcome; survival analysis; primary non-function; retransplant