Contribution of Liver Stiffness Measurement by Vibration-Controlled Transient Elastography to Outcome Prediction in Primary Biliary Cholangitis
Christophe Corpechot
(1, 2)
,
Fabrice Carrat
(3, 2)
,
Farid Gaouar
(2, 1)
,
Frédéric Chau
(2, 3)
,
Gideon Hirschfield
(4)
,
Aliya Gulamhusein
(4)
,
Aldo Montano-Loza
(5)
,
Ellina Lytvyak
(5)
,
Christoph Schramm
(6)
,
Albert Pares
(7, 8, 9)
,
Ignasi Olivas
(9, 8, 7)
,
John Eaton
(10)
,
Karim Osman
(10)
,
George Dalekos
(11)
,
Nikolaos Gatselis
(11)
,
Frederik Nevens
(12)
,
Nora Cazzagon
(13)
,
Alessandra Zago
(13)
,
Francesco Paolo Russo
(13)
,
Nadir Abbas
(14)
,
Palak Trivedi
(14)
,
Douglas Thorburn
(15)
,
Francesca Saffioti
(15)
,
Laszlo Barkai
(15)
,
Davide Roccarina
(15)
,
Vicenza Calvaruso
(16)
,
Anna Fichera
(16)
,
Adèle Delamarre
(17)
,
Esli Medina-Morales
(18)
,
Alan Bonder
(18)
,
Vilas Patwardhan
(18)
,
Cristina Rigamonti
(19)
,
Marco Carbone
(20)
,
Pietro Invernizzi
(20)
,
Laura Cristoferi
(20)
,
Adriaan van der Meer
(21)
,
Rozanne de Veer
(21)
,
Ehud Zigmond
(22)
,
Eyal Yehezkel
(22)
,
Andreas Kremer
(23)
,
Ansgar Deibel
(23)
,
Jérôme Dumortier
(24)
,
Tony Bruns
(25)
,
Karsten Große
(25)
,
Victor de Lédinghen
(17)
,
Georges‐philippe Pageaux
(26, 27)
,
Aaron Wetten
(28)
,
Jessica Dyson
(28)
,
David Jones
(28)
,
Olivier Chazouillères
(2, 1)
,
Bettina Hansen
(4)
1
CRSA -
Centre de Recherche Saint-Antoine
2 CHU Saint-Antoine [AP-HP]
3 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
4 University of Toronto
5 University of Alberta
6 UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
7 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
8 CIBERehd - Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas
9 University of Barcelona
10 Mayo Clinic [Rochester]
11 University Hospital of Larissa
12 University Hospitals Leuven [Leuven]
13 AOUP - Azienda Ospedale Università di Padova = Hospital-University of Padua
14 University of Birmingham [Birmingham]
15 Royal Free Hospital [London, UK]
16 Università degli studi di Palermo - University of Palermo
17 CHU Bordeaux
18 BIDMC - Beth Israel Deaconess Medical Center [Boston]
19 Università del Piemonte Orientale - Dipartimento DISIT Italy
20 UNIMIB - Università degli Studi di Milano-Bicocca = University of Milano-Bicocca
21 Erasmus MC - Erasmus University Medical Center [Rotterdam]
22 Tel Aviv Sourasky Medical Center [Te Aviv]
23 University hospital of Zurich [Zurich]
24 Service d'Hépatologie et de Gastroentérologie [Lyon]
25 UKA - Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany]
26 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
27 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
28 Newcastle University [Newcastle]
2 CHU Saint-Antoine [AP-HP]
3 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
4 University of Toronto
5 University of Alberta
6 UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
7 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
8 CIBERehd - Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas
9 University of Barcelona
10 Mayo Clinic [Rochester]
11 University Hospital of Larissa
12 University Hospitals Leuven [Leuven]
13 AOUP - Azienda Ospedale Università di Padova = Hospital-University of Padua
14 University of Birmingham [Birmingham]
15 Royal Free Hospital [London, UK]
16 Università degli studi di Palermo - University of Palermo
17 CHU Bordeaux
18 BIDMC - Beth Israel Deaconess Medical Center [Boston]
19 Università del Piemonte Orientale - Dipartimento DISIT Italy
20 UNIMIB - Università degli Studi di Milano-Bicocca = University of Milano-Bicocca
21 Erasmus MC - Erasmus University Medical Center [Rotterdam]
22 Tel Aviv Sourasky Medical Center [Te Aviv]
23 University hospital of Zurich [Zurich]
24 Service d'Hépatologie et de Gastroentérologie [Lyon]
25 UKA - Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany]
26 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
27 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
28 Newcastle University [Newcastle]
Christophe Corpechot
- Fonction : Auteur
- PersonId : 1090556
- IdHAL : christophecorpechotaphpfr
Fabrice Carrat
- Fonction : Auteur
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Ellina Lytvyak
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Christoph Schramm
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George Dalekos
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Nikolaos Gatselis
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Nora Cazzagon
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Alessandra Zago
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Nadir Abbas
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Francesca Saffioti
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Davide Roccarina
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Esli Medina-Morales
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Alan Bonder
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Cristina Rigamonti
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Pietro Invernizzi
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Laura Cristoferi
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Adriaan van der Meer
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Eyal Yehezkel
- Fonction : Auteur
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Andreas Kremer
- Fonction : Auteur
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Ansgar Deibel
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Jérôme Dumortier
- Fonction : Auteur
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Tony Bruns
- Fonction : Auteur
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Georges‐philippe Pageaux
- Fonction : Auteur
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Aaron Wetten
- Fonction : Auteur
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Jessica Dyson
- Fonction : Auteur
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Résumé
Background & aims: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) has been shown to predict outcomes of patients with primary biliary cholangitis (PBC) in small-size studies. We aimed to validate the prognostic value of LSM in a large cohort study.
Methods: We performed an international, multicentre, retrospective follow-up study of 3,985 patients with PBC seen at 23 centres in 12 countries. Eligibility criteria included at least 1 reliable LSM by VCTE and a follow-up ≥ 1 year. Independent derivation (n = 2,740) and validation (n = 568) cohorts were built. The primary endpoint was time to poor clinical outcomes defined as liver-related complications, liver transplantation, or death. Hazard ratios (HRs) with CIs were determined using a time-dependent multivariable Cox regression analysis.
Results: LSM was independently associated with poor clinical outcomes in the derivation (5,324 LSMs, mean follow-up 5.0 ± 3.1 years) and validation (1,470 LSMs, mean follow-up 5.0 ± 2.8 years) cohorts: adjusted HRs (95% CI) per additional kPa were 1.040 (1.026-1.054) and 1.042 (1.029-1.056), respectively (p <0.0001 for both). Adjusted C-statistics (95% CI) at baseline were 0.83 (0.79-0.87) and 0.92 (0.89-0.95), respectively. Between 5 and 30 kPa, the log-HR increased as a monotonic function of LSM. The predictive value of LSM was stable in time. LSM improved the prognostic ability of biochemical response criteria, fibrosis scores, and prognostic scores. The 8 kPa and 15 kPa cut-offs optimally separated low-, medium-, and high-risk groups. Forty percent of patients were at medium to high risk according to LSM.
Conclusions: LSM by VCTE is a major, independent, validated predictor of PBC outcome. Its value as a surrogate endpoint for clinical benefit in PBC should be considered.
Lay summary: Primary biliary cholangitis (PBC) is a chronic autoimmune disease, wherein the body's immune system mistakenly attacks the bile ducts. PBC progresses gradually, so surrogate markers (markers that predict clinically relevant outcomes like the need for a transplant or death long before the event occurs) are often needed to expedite the drug development and approval process. Herein, we show that liver stiffness measurement is a strong predictor of clinical outcomes and could be a useful surrogate endpoint in PBC trials.
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