Liver Transplantation in Patients With CirrHosis and Severe Acute-on-Chronic Liver Failure: iNdications and outComEs

Study Overview
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Brief Summary
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Management of ACLF is mainly supportive. The poor outcomes lead physicians to consider liver transplantation as an option, even if controversial. In sicker recipients, LT results in immediate survival, but poor medium-term survival rates in some studies. The scarcity of deceased donors obliges to maximize LT success. Alternative strategies, as living-donor LT, should be explored. LDLT has impressive results in Eastern centers, but it is restrained in Western countries, due to potential life-threatening complications in the donor.

Detailed Description
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The aim of this study is to compare 1-year graft and patient survival rates after liver transplantation (LT) in patients with ACLF-2 or 3 at the time of LT, with patients with decompensated cirrhosis without ACLF-2 or 3 at the time of LT and also with transplant-free survival of patients with ACLF-2 or 3 not listed for LT. Secondary objectives are as follows: To assess the proportion of patients with ACLF-2 or 3 referred to transplant team who are listed or not and reasons of this decision. To evaluate the outcomes of patients listed with ACLF-2 or 3 on the waiting list compared with those of patients listed with decompensated cirrhosis without ACLF-2 or 3. To define independent predictive factors of death/delisting on the waiting list for patients listed with ACLF-2 or 3 and develop a new prognostic model based on ACLF criteria to predict mortality on the waiting list and to improve the allocation of organs. To compare the characteristics of accepted grafts for patients listed with ACLF-2 or 3 with those of patients listed with decompensated cirrhosis without ACLF-2 or 3 and their impact on post-LT outcomes. To explore independent predictive factors of death after LT for patients transplanted with ACLF-2 or 3 to design futility criteria for LT. To compare post-LT survival rates of patients with ACLF-2 or 3 at listing and patients without ACLF at listing who develop ACLF-2 or 3 on the waiting list. To compare post-LT quality of life (QoL) for patients listed with ACLF-2 or 3 with those of patients listed with decompensated cirrhosis without ACLF-2 or 3.

Official Title
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Liver Transplantation in Patients With CirrHosis and Severe Acute-on-Chronic Liver Failure (ACLF): iNdications and outComEs

Conditions
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Liver Diseases, Liver Cirrhosis, Acute-On-Chronic Liver Failure, Liver Transplant; Complications

Intervention / Treatment
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* Other: Observational Protocol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Male or female subject ≥18 years of age. 2. Subjects with diagnosis of liver cirrhosis (based on clinical, laboratory, endoscopic, and ultrasonographic features or on histology). 3. Subjects who have been hospitalized for acute decompensation of liver cirrhosis and referred to the transplant team: Group 1: patients listed for liver transplantation with ACLF-2 or 3 at the time of listing or developing ACLF 2-3 while on the waiting list. Group 2: patients listed for liver transplantation with decompensated cirrhosis without ACLF-2 or 3 and poor liver function (MELD>20) at the time of listing. Group 3: patients having ACLF-2 or 3, are assessed for inclusion in the waiting list, but are finally not listed for liver transplantation. 4. Patients (or trusted person, family member or close relation if the patient is unable to express consent) who have been informed and signed their informed consent Inclusion criteria Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>patients listed for liver transplantation with ACLF-2 or 3 at the time of listing or developing ACLF 2-3 while on the waiting list (n=2,000) | Other: Observational Protocol<br>* The cohorts will be followed for one year after LT transplantation except for group 3 (1-year follow-up after inclusion)<br>|
| Group 2<br>patients listed for liver transplantation with decompensated cirrhosis without ACLF-2 or 3 and poor liver function (MELD > 20) at the time of listing (n=500) | Other: Observational Protocol<br>* The cohorts will be followed for one year after LT transplantation except for group 3 (1-year follow-up after inclusion)<br>|
| Group 3<br>patients having ACLF-2 or 3, are assessed for inclusion in the waiting list, but are finally not listed for liver transplantation (n=500) | Other: Observational Protocol<br>* The cohorts will be followed for one year after LT transplantation except for group 3 (1-year follow-up after inclusion)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | survival | 1 year |