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

NCT ID: NCT04613921

Last Updated: 2025-10-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

3000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-07-08

Study Completion Date

2026-12-31

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.

Conditions

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

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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 (n=2,000)

Observational Protocol

Intervention Type OTHER

The cohorts will be followed for one year after LT transplantation except for group 3 (1-year follow-up after inclusion)

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 (n=500)

Observational Protocol

Intervention Type OTHER

The cohorts will be followed for one year after LT transplantation except for group 3 (1-year follow-up after inclusion)

Group 3

patients having ACLF-2 or 3, are assessed for inclusion in the waiting list, but are finally not listed for liver transplantation (n=500)

Observational Protocol

Intervention Type OTHER

The cohorts will be followed for one year after LT transplantation except for group 3 (1-year follow-up after inclusion)

Interventions

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Observational Protocol

The cohorts will be followed for one year after LT transplantation except for group 3 (1-year follow-up after inclusion)

Intervention Type OTHER

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.

Exclusion Criteria

\-
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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European Foundation for Study of Chronic Liver Failure

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Cedars-Sinai Comprehensive Transplant Center

Los Angeles, California, United States

Site Status RECRUITING

University of Colorado

Aurora, Colorado, United States

Site Status RECRUITING

Tampa General Hospital

Tampa, Florida, United States

Site Status NOT_YET_RECRUITING

Piedmont Healthcare

Atlanta, Georgia, United States

Site Status RECRUITING

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status NOT_YET_RECRUITING

The University of Chicago Medicine

Chicago, Illinois, United States

Site Status RECRUITING

University of Maryland School of Medicine

Baltimore, Maryland, United States

Site Status RECRUITING

Weill Cornell Medicine

New York, New York, United States

Site Status RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status RECRUITING

Montefiore Medical Center

New York, New York, United States

Site Status NOT_YET_RECRUITING

University of Cincinnati

Cincinnati, Ohio, United States

Site Status SUSPENDED

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status SUSPENDED

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status NOT_YET_RECRUITING

Baylor College of Medicine (Scott & White)

Dallas, Texas, United States

Site Status NOT_YET_RECRUITING

Michael E DeBakey VA Medical Center

Houston, Texas, United States

Site Status NOT_YET_RECRUITING

Baylor St. Luke's Medical Centre

Houston, Texas, United States

Site Status RECRUITING

University of Utah Health

Salt Lake City, Utah, United States

Site Status RECRUITING

Austral University Hospital

Buenos Aires, , Argentina

Site Status RECRUITING

Hospital Alemán

Buenos Aires, , Argentina

Site Status RECRUITING

Italian Hospital in Buenos Aires

Buenos Aires, , Argentina

Site Status RECRUITING

Austin Hospital

Heidelberg, , Australia

Site Status RECRUITING

Sir Charles Gairdner Hospital

Nedlands, , Australia

Site Status SUSPENDED

Royal Prince Alfred Hospital

Sydney, , Australia

Site Status RECRUITING

Medical University of Vienna, Department of Transplant Surgery

Vienna, , Austria

Site Status RECRUITING

CUB Erasme Hospital

Brussels, , Belgium

Site Status RECRUITING

Ghent University Hospital

Ghent, , Belgium

Site Status RECRUITING

UZ Leuven

Leuven, , Belgium

Site Status RECRUITING

Walter Cantídio University Hospital

Fortaleza, , Brazil

Site Status RECRUITING

Irmandade Santa Casa de Misericórdia de Porto Alegre

Porto Alegre, , Brazil

Site Status RECRUITING

Hospital das Clínicas da Universidade de São Paulo

São Paulo, , Brazil

Site Status RECRUITING

University of Alberta

Edmonton, , Canada

Site Status RECRUITING

University of Toronto, Multiorgan Transplant Program

Toronto, , Canada

Site Status RECRUITING

Pablo Tobón Uribe Hospital

Medellín, , Colombia

Site Status RECRUITING

Institute for Clinical and Experimental Medicine

Prague, , Czechia

Site Status NOT_YET_RECRUITING

APHP Beaujon

Clichy, , France

Site Status RECRUITING

APHP Henri Mondor

Créteil, , France

Site Status RECRUITING

Hôpital de la Croix-Rousse

Lyon, , France

Site Status RECRUITING

CHU Montpellier-Hôpital Saint Eloi

Montpellier, , France

Site Status RECRUITING

APHP Hôpitaux Universitaires Pitié Salpêtrière

Paris, , France

Site Status RECRUITING

CHU Rennes, Hôpital De Pontchaillou

Rennes, , France

Site Status RECRUITING

Hautepièrre Hospital, Service de Réanimation Médicale

Strasbourg, , France

Site Status RECRUITING

Trousseau Hospital,

Tours, , France

Site Status RECRUITING

Hôpital Paul Brousse

Villejuif, , France

Site Status RECRUITING

University Hospital Regensburg

Regensburg, Eastern Bavaria, Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Schleswig-Holstein (UKSH)

Kiel, Schleswig-Holstein, Germany

Site Status NOT_YET_RECRUITING

University Hospital Aachen

Aachen, , Germany

Site Status SUSPENDED

Charité University Hospital

Berlin, , Germany

Site Status RECRUITING

Goethe University Clinic

Frankfurt, , Germany

Site Status NOT_YET_RECRUITING

University Medical Center, Hamburg Eppendorf

Hamburg, , Germany

Site Status RECRUITING

Hannover Medical School

Hanover, , Germany

Site Status NOT_YET_RECRUITING

University Hospital Heidelberg

Heidelberg, , Germany

Site Status NOT_YET_RECRUITING

Jena University Hospital

Jena, , Germany

Site Status SUSPENDED

Universitätsklinikum Schleswig-Holstein (UKSH)

Kiel, , Germany

Site Status RECRUITING

Leipzig University Hospital

Leipzig, , Germany

Site Status NOT_YET_RECRUITING

University Hospital Mainz

Mainz, , Germany

Site Status SUSPENDED

LMU Großhadern

Munich, , Germany

Site Status SUSPENDED

UKM Muenster

Münster, , Germany

Site Status RECRUITING

University Hospital Tübingen

Tübingen, , Germany

Site Status RECRUITING

Queen Mary Hospital, The University of Hong Kong

Hong Kong, , Hong Kong

Site Status SUSPENDED

Aster CMI Hospital

Bengaluru, Karnataka, India

Site Status NOT_YET_RECRUITING

Kasturba Hospital

Mumbai, Maharashtra, India

Site Status NOT_YET_RECRUITING

Seth GSMC & KEM Hospital

Mumbai, Maharashtra, India

Site Status NOT_YET_RECRUITING

Indraprastha Apollo Hospitals

New Delhi, National Capital Territory of Delhi, India

Site Status NOT_YET_RECRUITING

Mahatma Gandhi University of Medical Sciences and Technology

Jaipur, Rajasthan, India

Site Status NOT_YET_RECRUITING

Dr.Rela Institute & Medical Centre

Chennai, , India

Site Status RECRUITING

Fortis Hospital Noida, FEHI, FMRI

Gurugramam, , India

Site Status NOT_YET_RECRUITING

Medanta Medicity

Gurugramam, , India

Site Status NOT_YET_RECRUITING

Amrita Institute of Medical Sciences

Kochi, , India

Site Status RECRUITING

Global Hospital. Super speciality & transplant centre

Mumbai, , India

Site Status NOT_YET_RECRUITING

Max Saket Hospital

New Delhi, , India

Site Status ACTIVE_NOT_RECRUITING

Yashoda Hospitals

Secunderabad, , India

Site Status NOT_YET_RECRUITING

Ospedale Papa Giovanni XXIII-

Bergamo, , Italy

Site Status NOT_YET_RECRUITING

S.Orsola Hospital - Alma Mater Studiorum University of Bologna

Bologna, , Italy

Site Status RECRUITING

Ca' Granda. Policlinico Milano

Milan, , Italy

Site Status RECRUITING

Niguarda Hospital

Milan, , Italy

Site Status RECRUITING

University and Hospital of Padova

Padua, , Italy

Site Status RECRUITING

Kyushu University Hospital

Fukuoka, , Japan

Site Status RECRUITING

Hiroshima University Hospital

Hiroshima, , Japan

Site Status RECRUITING

Kyoto University Hospital

Kyoto, , Japan

Site Status RECRUITING

Nagasaki University Hospital

Nagasaki, , Japan

Site Status RECRUITING

Tokyo University Hospital

Tokyo, , Japan

Site Status RECRUITING

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Mexico City, , Mexico

Site Status RECRUITING

University Medical Center Groningen (UMCG)

Groningen, , Netherlands

Site Status NOT_YET_RECRUITING

Erasmus MC University Medical Center

Rotterdam, , Netherlands

Site Status RECRUITING

Auckland City Hospital- New Zealand Liver Transplant Unit

Auckland, , New Zealand

Site Status SUSPENDED

Medical University of Warsaw, Dept. of General, Transplant & Liver Surgery

Warsaw, , Poland

Site Status RECRUITING

Hospital Curry Cabral

Lisbon, , Portugal

Site Status RECRUITING

Samsung Medical Center

Seoul, , South Korea

Site Status NOT_YET_RECRUITING

Hospital Clinic in Barcelona

Barcelona, , Spain

Site Status RECRUITING

Hospital Vall d'Hebron

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Site Status RECRUITING

Hospital Marqués de Valdecilla

Santander, , Spain

Site Status RECRUITING

Hospital Universitario Virgen del Rocío

Seville, , Spain

Site Status RECRUITING

Hospital Universitari i Politècnic La Fe

Valencia, , Spain

Site Status RECRUITING

Karolinska Institutet

Stockholm, Stockholm County, Sweden

Site Status RECRUITING

Geneva University Hospital (HUG)

Geneva, , Switzerland

Site Status NOT_YET_RECRUITING

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Site Status RECRUITING

Inonu University, Liver Transplantation Institute

Malatya, Anatolia, Turkey (Türkiye)

Site Status RECRUITING

Istanbul Memorial Bahcelievler Hospital

Istanbul, , Turkey (Türkiye)

Site Status SUSPENDED

Queen Elizabeth Hospital Birmingham

Birmingham, , United Kingdom

Site Status RECRUITING

Scottish Liver Transplant Unit, Royal Infirmary

Edinburgh, , United Kingdom

Site Status RECRUITING

Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

Site Status RECRUITING

King's College Hospital

London, , United Kingdom

Site Status RECRUITING

Royal Free Hospital

London, , United Kingdom

Site Status RECRUITING

Countries

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United States Argentina Australia Austria Belgium Brazil Canada Colombia Czechia France Germany Hong Kong India Italy Japan Mexico Netherlands New Zealand Poland Portugal South Korea Spain Sweden Switzerland Taiwan Turkey (Türkiye) United Kingdom

Central Contacts

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Anna Bosch

Role: CONTACT

34 93 227 1400

Facility Contacts

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Alexander Kuo

Role: primary

Michael Kriss

Role: primary

303-724-1030

Nyingi Kemmer

Role: primary

Lance Stein

Role: primary

Justin R Boike

Role: primary

+1 312-926-2000

Helen Te

Role: primary

Kirti Shetty

Role: primary

410 3281328

Russell Rosenblatt

Role: primary

646-962-5483

Ghideon Ezaz

Role: primary

Brett Fortune

Role: primary

+1 718-920-4321

Bijan Eghtesad

Role: primary

Manhal Izzy

Role: primary

+1 615-322-5000

Amar Gupta

Role: primary

Rubén Hernáez

Role: primary

Jalal Prasun

Role: primary

Juan Gallegos-Orozco

Role: primary

801.581.7878

Marcelo Silva

Role: primary

54 0230 448 - 2422

María Margarita Anders

Role: primary

54 11 4827-7000 ext. 2320

Sebastián Marciano

Role: primary

54-11-49590200 ext. 5370

Marie Sinclair

Role: primary

Avik Majumdar

Role: primary

Gabriela Berlakovitch

Role: primary

Andreas Rosenstingl

Role: backup

Thierry Gustot

Role: primary

Hans Van Vlierberghe

Role: primary

Xavier Verhelst

Role: backup

Wim Laleman

Role: primary

Lívia Carone Linhares

Role: primary

+55 85 3366-8167

Ângelo Zambam de Mattos

Role: primary

+55 51 3214-8080

Alberto Farias

Role: primary

+55 11 2661-0000

Dean Karvellas

Role: primary

Nazia Selzner

Role: primary

Juan Ignacio Marín

Role: primary

+57 604 4459000

Eva Kieslichová

Role: primary

Pavel Taimr

Role: backup

François Durand

Role: primary

Christophe Duvoux

Role: primary

Sylvie Radenne

Role: primary

Georges Phlippe Pageaux

Role: primary

Filomena Conti

Role: primary

Pauline Houssel-Debry

Role: primary

Thierry Artzner

Role: primary

Laure Elkrief

Role: primary

Didier Samuel

Role: primary

Martina Müller-Schilling, MD

Role: primary

Thomas Becker, Prof

Role: primary

Cornelius Engelmann

Role: primary

Alexander Queck

Role: primary

Lutz Fischer

Role: primary

Richard Taubert

Role: primary

Arianeb Mehrabi

Role: primary

Thomas Becker

Role: primary

Thomas Berg

Role: primary

Jonel Trebicka

Role: primary

Silvio Nadalin

Role: primary

Sonal Asthana, MD

Role: primary

Shiran Shetty, MD

Role: primary

Akash Shukla

Role: primary

Ashish Malik, MD

Role: primary

Vivek Saraswat, Prof

Role: primary

Mohamed Rela, PI

Role: primary

+91 44 6666 7788

Ashwin Ramohan

Role: backup

Vivek Vij, PI

Role: primary

Arvinder Singh Soin

Role: primary

S Sudhindran

Role: primary

+91 484 285 1234

Samir Shah, Pi

Role: primary

Darmesh Kapoor, PI

Role: primary

Stefano Fagiouli

Role: primary

Cristina Morelli

Role: primary

Angelo Sangiovanni

Role: primary

Giovanni Perricone

Role: primary

39 02 6444.4454

Salvatore Piano

Role: primary

Tomoharo Yoshizumi

Role: primary

Masahiro Ohira

Role: primary

Shintaro Yagi

Role: primary

Takanobu Hara

Role: primary

81 095-819-7316

Nobuhisa Akamatsu

Role: primary

Graciela Elia Castro Narro

Role: primary

+52 55 5487 0900

Aad Van den Berg

Role: primary

Caroline Den Hoed

Role: primary

Krzysztof Zieniewicz

Role: primary

Luis Bagulho

Role: primary

Jong Man Kim

Role: primary

Javier Fernández Gómez

Role: primary

934932271400

Isabel Campos

Role: primary

Víctor Vargas

Role: backup

Carmelo Loinaz

Role: primary

Agustín Albillos

Role: primary

José Ignacio Fortea

Role: primary

Miguel Ángel Gómez Bravo

Role: primary

Marina Carmen Berenguer Haym

Role: primary

Magnus Holmer, PI

Role: primary

08-524 800 00

Christina Villard, PI

Role: backup

08-524 800 00

Christian Toso

Role: primary

Chee Chien Yong

Role: primary

Sezai Yilmaz, Prof

Role: primary

Abhishek Chauhab

Role: primary

Ken Simpson

Role: primary

Joanna Moore

Role: primary

William Bernal

Role: primary

Rajiv Jalan

Role: primary

442074332795

References

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Gustot T, Fernandez J, Garcia E, Morando F, Caraceni P, Alessandria C, Laleman W, Trebicka J, Elkrief L, Hopf C, Solis-Munoz P, Saliba F, Zeuzem S, Albillos A, Benten D, Montero-Alvarez JL, Chivas MT, Concepcion M, Cordoba J, McCormick A, Stauber R, Vogel W, de Gottardi A, Welzel TM, Domenicali M, Risso A, Wendon J, Deulofeu C, Angeli P, Durand F, Pavesi M, Gerbes A, Jalan R, Moreau R, Gines P, Bernardi M, Arroyo V; CANONIC Study Investigators of the EASL-CLIF Consortium. Clinical Course of acute-on-chronic liver failure syndrome and effects on prognosis. Hepatology. 2015 Jul;62(1):243-52. doi: 10.1002/hep.27849. Epub 2015 May 29.

Reference Type BACKGROUND
PMID: 25877702 (View on PubMed)

Artru F, Louvet A, Ruiz I, Levesque E, Labreuche J, Ursic-Bedoya J, Lassailly G, Dharancy S, Boleslawski E, Lebuffe G, Kipnis E, Ichai P, Coilly A, De Martin E, Antonini TM, Vibert E, Jaber S, Herrerro A, Samuel D, Duhamel A, Pageaux GP, Mathurin P, Saliba F. Liver transplantation in the most severely ill cirrhotic patients: A multicenter study in acute-on-chronic liver failure grade 3. J Hepatol. 2017 Oct;67(4):708-715. doi: 10.1016/j.jhep.2017.06.009. Epub 2017 Jun 21.

Reference Type BACKGROUND
PMID: 28645736 (View on PubMed)

Sundaram V, Jalan R, Wu T, Volk ML, Asrani SK, Klein AS, Wong RJ. Factors Associated with Survival of Patients With Severe Acute-On-Chronic Liver Failure Before and After Liver Transplantation. Gastroenterology. 2019 Apr;156(5):1381-1391.e3. doi: 10.1053/j.gastro.2018.12.007. Epub 2018 Dec 18.

Reference Type BACKGROUND
PMID: 30576643 (View on PubMed)

Other Identifiers

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2020/01325

Identifier Type: -

Identifier Source: org_study_id

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