Early Allograft Failure Simplified Estimation (EASE) in Liver Transplantation (EASE)

Early Allograft Failure Simplified Estimation (EASE). A Novel Predictive Model for Estimating Early Allograft Failure in Liver Transplantation: a Multicenter Italian Study With a UK Validation Cohort.

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.

Study Overview

• Status: Completed
• Conditions: Liver Transplant Failure
• Intervention / Treatment: Procedure: Liver transplantation

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.

• Study Type: Observational
• Enrollment (Actual): 2350

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario A. Gemelli, IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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).

Description

Inclusion Criteria:

• Primary liver transplants from deceased donors

Exclusion Criteria:

• combined transplants (liver transplanted simultaneously with another organ transplant)
• living donor liver transplant
• domino liver transplant
• pediatric transplants
• HIV+ recipients

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Training set; Cohort of consecutive liver transplants performed in 2016-2017 from 14 liver transplant centers in Italy	Procedure: Liver transplantation; Liver transplantation from deceased donors
Validation set; Cohort of consecutive liver transplants performed in 2016-2017 from 2 liver transplant centers in the United Kingdom	Procedure: Liver transplantation; Liver transplantation from deceased donors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early Allograft Failure	Graft loss after liver transplantation	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early Allograft Failure	Graft loss after liver transplantation	30 days

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Collaborators: Azienda Ospedaliera Città della Salute e della Scienza di Torino; IRCCS Azienda Ospedaliero-Universitaria di Bologna; Azienda Ospedaliero, Universitaria Pisana; University of Roma La Sapienza; Azienda Ospedaliera Universitaria Integrata Verona; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; University Hospital Birmingham NHS Foundation Trust; Newcastle-upon-Tyne Hospitals NHS Trust; Azienda Ospedaliero-Universitaria di Modena; Azienda Ospedaliera Niguarda Cà Granda; University Hospital Padova; A.O. Ospedale Papa Giovanni XXIII; The Mediterranean Institute for Transplantation and Advanced Specialized Therapies; Ospedali Riuniti Ancona
• Investigators: Principal Investigator: Alfonso W Avolio, MD, alfonso.avolio@unicatt.it

Publications and helpful links

General Publications

• Agopian VG, Harlander-Locke MP, Markovic D, Dumronggittigule W, Xia V, Kaldas FM, Zarrinpar A, Yersiz H, Farmer DG, Hiatt JR, Busuttil RW. Evaluation of Early Allograft Function Using the Liver Graft Assessment Following Transplantation Risk Score Model. JAMA Surg. 2018 May 1;153(5):436-444. doi: 10.1001/jamasurg.2017.5040. Erratum In: JAMA Surg. 2018 May 1;153(5):498.

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2018
• Primary Completion (Actual): November 28, 2018
• Study Completion (Actual): January 10, 2019

Study Registration Dates

• First Submitted: February 27, 2019
• First Submitted That Met QC Criteria: February 27, 2019
• First Posted (Actual): February 28, 2019

Study Record Updates

• Last Update Posted (Actual): March 1, 2019
• Last Update Submitted That Met QC Criteria: February 28, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: retransplant; liver transplant; primary non-function; allograft failure; primary dysfunction; early outcome; survival analysis
• Other Study ID Numbers: Prot. 35355/18 ID:2232

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No