Liver transplantation in patients with CirrHosis and severe Acute-on-Chronic Liver Failure

Recruiting

Conditions: Other and unspecified cirrhosis ofliver,

Registration Number: CTRI/2022/06/042973

Lead Sponsor: EASLCLIF Consortium

Brief Summary: 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.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: Open to Recruitment

Sex: All

Target Recruitment: 3000

Inclusion Criteria

Male or female subject â‰¥18 years of age.
Subjects with diagnosis of liver cirrhosis (based on clinical, laboratory, endoscopic, and ultrasonographic features or on histology).
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.
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

A subject meeting any of the following exclusion criteria is NOT eligible for participation in the study.
1.Acute or subacute liver failure without underlying cirrhosis.
2.Patients with hepatocellular carcinoma outside Milan criteria or other active neoplasia.
3.Subjects listed for transplantation other than liver or liver-kidney transplant.
4.Subjects with previous liver transplantation.
5.Vulnerable population (person under temporary or permanent guardianship or deprived of liberty by a judicial decision).
6.Pregnant and/or breastfeeding woman 7.Patients with relevant comorbidities that could impact the prognosis: oSubjects with very severe hepatopulmonary syndrome (with PaO2 < 50 mmHg on FiO2 21%) or moderate to severe portopulmonary hypertension (non-reversible mPAP â‰¥ 35 mmHg or PVR â‰¥ 500 dyn.s.cm-5).
oSubjects with severe (grade IV) pulmonary disease (Global Obstructive Lung Disease [GOLD]).
oSubjects with chronic kidney disease requiring hemodialysis oSubjects with severe heart disease (NYHA class III and IV) oSubjects with a known infection with human immunodeficiency virus (HIV) oSubjects with severe neurological or psychiatric disorders 8.Patients who cannot provide prior informed consent and when there is documented evidence that the patient has no legal surrogate decision maker and it appears unlikely that the patient will regain consciousness or sufficient ability to provide delayed informed consent.
9.Physician and team not committed to provide intensive care if needed.

Study & Design

Study Type: Observational

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 transplant-free survival of patients with ACLF-2 or 3 not listed for LT.	1 year

Secondary Outcome Measures

Name	Time	Method
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.	1 year
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.	1 year
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.	1 year
-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.	1 year
-To assess the resources utilization for patients listed with ACLF-2 or 3 (in intention-to-treat and per protocol) compared with patients listed with decompensated cirrhosis without ACLF-2 or 3.	1 year

Trial Locations

Locations (4): Amrita Institute of Medical Science
🇮🇳
Ernakulam, KERALA, India
Dr Rela Institute and Medical Centre
🇮🇳
Chennai, TAMIL NADU, India
Global Hospitals Mumbai
🇮🇳
Mumbai, MAHARASHTRA, India
Yashoda Hospitals
🇮🇳
Hyderabad, TELANGANA, India
Amrita Institute of Medical Science
🇮🇳Ernakulam, KERALA, India
S Sudhindran
Principal investigator
04846681234
sudhisalini@icloud.com