Dynamics of Liver Stiffness Measurement and Clinical Course of Primary Biliary Cholangitis

Laurent Lam; Pierre Antoine Soret; Global & ERN Rare-Liver PBC Study Groups; Sara Lemoinne; Bettina Hansen; Gideon Hirschfield; Aliya Gulamhusein; Aldo J. Montano-Loza; Ellina Lytvyak; Albert Parés; Ignasi Olivas; Maria Carlota Londono; Sergio Rodríguez-Tajes; John E. Eaton; Karim T. Osman; Christoph Schramm; Marcial Sebode; Ansgar W. Lohse; George Dalekos; Nikolaos Gatselis; Frederik Nevens; Nora Cazzagon; Alessandra Zago; Francesco Paolo Russo; Annarosa Floreani; Nadir Abbas; Palak Trivedi; Douglas Thorburn; Francesca Saffioti; Laszlo Barkai; Davide Roccarina; Vicenza Calvaruso; Anna Fichera; Adèle Delamarre; Natalia Sobenko; Alejandra Maria Villamil; Esli Medina-Morales; Alan Bonder; Vilas Patwardhan; Cristina Rigamonti; Marco Carbone; Pietro Invernizzi; Laura Cristoferi; Adriaan van der Meer; Rozanne de Veer; Ehud Zigmond; Eyal Yehezkel; Andreas E. Kremer; Ansgar Deibel; Tony Bruns; Karsten Große; Aaron Wetten; Jessica Dyson; David Jones; Cynthia Levy; Atsushi Tanaka; Jérôme Dumortier; George Philippe Pageaux; Victor De Lédinghen; Fabrice Carrat; Olivier Chazouillères; Christophe Corpechot

doi:10.1016/j.cgh.2024.06.035

Dynamics of Liver Stiffness Measurement and Clinical Course of Primary Biliary Cholangitis

Laurent Lam, Pierre Antoine Soret, Global & ERN Rare-Liver PBC Study Groups, Sara Lemoinne, Bettina Hansen, Gideon Hirschfield, Aliya Gulamhusein, Aldo J. Montano-Loza, Ellina Lytvyak, Albert Parés, Ignasi Olivas, Maria Carlota Londono, Sergio Rodríguez-Tajes, John E. Eaton, Karim T. Osman, Christoph Schramm, Marcial Sebode, Ansgar W. Lohse, George Dalekos, Nikolaos GatselisFrederik Nevens, Nora Cazzagon, Alessandra Zago, Francesco Paolo Russo, Annarosa Floreani, Nadir Abbas, Palak Trivedi, Douglas Thorburn, Francesca Saffioti, Laszlo Barkai, Davide Roccarina, Vicenza Calvaruso, Anna Fichera, Adèle Delamarre, Natalia Sobenko, Alejandra Maria Villamil, Esli Medina-Morales, Alan Bonder, Vilas Patwardhan, Cristina Rigamonti, Marco Carbone, Pietro Invernizzi, Laura Cristoferi, Adriaan van der Meer, Rozanne de Veer, Ehud Zigmond, Eyal Yehezkel, Andreas E. Kremer, Ansgar Deibel, Tony Bruns, Karsten Große, Aaron Wetten, Jessica Dyson, David Jones, Cynthia Levy, Atsushi Tanaka, Jérôme Dumortier, George Philippe Pageaux, Victor De Lédinghen, Fabrice Carrat, Olivier Chazouillères, Christophe Corpechot^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

3 Citations (Scopus)

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Abstract

Background & Aims:

In primary biliary cholangitis (PBC), static liver stiffness measurement (LSM) has proven prognostic value. However, the added prognostic value of LSM time course in this disease remains uncertain.

Methods:

We conducted an international retrospective cohort study among patients with PBC treated with ursodeoxycholic acid and followed by vibration-controlled transient elastography between 2003 and 2022. Using joint modeling, the association of LSM trajectory and the incidence of serious clinical events (SCE), defined as cirrhosis complications, liver transplantation, or death, was quantified using the hazard ratio and its confidence interval.

Results:

A total of 6362 LSMs were performed in 3078 patients (2007 on ursodeoxycholic acid alone; 13% with cirrhosis), in whom 316 SCE occurred over 14,445 person-years (median follow-up, 4.2 years; incidence rate, 21.9 per 1000 person-years). LSM progressed in 59% of patients (mean, 0.39 kPa/year). After adjusting for prognostic factors at baseline, including LSM, any relative change in LSM was associated with a significant variation in SCE risk (P < .001). For example, the adjusted hazard ratios (95% confidence interval) associated with a 20% annual variation in LSM were 2.13 (1.89–2.45) for the increase and 0.40 (0.33–0.46) for the decrease. The association between LSM trajectory and SCE risk persisted regardless of treatment response or duration, when patients with cirrhosis were excluded, and when only death or liver transplantation was considered.

Conclusions:

Tracking longitudinal changes in LSM using vibration-controlled transient elastography provides valuable insights into PBC prognosis, offering a robust predictive measure for the risk of SCE. LSM could be used as a clinically relevant surrogate end point in PBC clinical trials.

Original language	English
Pages (from-to)	2432-2441.e2
Journal	Clinical Gastroenterology and Hepatology
Volume	22
Issue number	12
DOIs	https://doi.org/10.1016/j.cgh.2024.06.035
Publication status	Published - Dec 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

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Dynamics of Liver Stiffness Measurement and Clinical Course of Primary Biliary CholangitisFinal published version, 2.14 MBLicence: CC BY

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Lam, L., Soret, P. A., Global & ERN Rare-Liver PBC Study Groups, Lemoinne, S., Hansen, B., Hirschfield, G., Gulamhusein, A., Montano-Loza, A. J., Lytvyak, E., Parés, A., Olivas, I., Londono, M. C., Rodríguez-Tajes, S., Eaton, J. E., Osman, K. T., Schramm, C., Sebode, M., Lohse, A. W., Dalekos, G., ... Corpechot, C. (2024). Dynamics of Liver Stiffness Measurement and Clinical Course of Primary Biliary Cholangitis. Clinical Gastroenterology and Hepatology, 22(12), 2432-2441.e2. https://doi.org/10.1016/j.cgh.2024.06.035

@article{df6168a71a0d42639c8f0db936bd1383,

title = "Dynamics of Liver Stiffness Measurement and Clinical Course of Primary Biliary Cholangitis",

abstract = "Background & Aims: In primary biliary cholangitis (PBC), static liver stiffness measurement (LSM) has proven prognostic value. However, the added prognostic value of LSM time course in this disease remains uncertain.Methods: We conducted an international retrospective cohort study among patients with PBC treated with ursodeoxycholic acid and followed by vibration-controlled transient elastography between 2003 and 2022. Using joint modeling, the association of LSM trajectory and the incidence of serious clinical events (SCE), defined as cirrhosis complications, liver transplantation, or death, was quantified using the hazard ratio and its confidence interval. Results: A total of 6362 LSMs were performed in 3078 patients (2007 on ursodeoxycholic acid alone; 13% with cirrhosis), in whom 316 SCE occurred over 14,445 person-years (median follow-up, 4.2 years; incidence rate, 21.9 per 1000 person-years). LSM progressed in 59% of patients (mean, 0.39 kPa/year). After adjusting for prognostic factors at baseline, including LSM, any relative change in LSM was associated with a significant variation in SCE risk (P < .001). For example, the adjusted hazard ratios (95% confidence interval) associated with a 20% annual variation in LSM were 2.13 (1.89–2.45) for the increase and 0.40 (0.33–0.46) for the decrease. The association between LSM trajectory and SCE risk persisted regardless of treatment response or duration, when patients with cirrhosis were excluded, and when only death or liver transplantation was considered. Conclusions: Tracking longitudinal changes in LSM using vibration-controlled transient elastography provides valuable insights into PBC prognosis, offering a robust predictive measure for the risk of SCE. LSM could be used as a clinically relevant surrogate end point in PBC clinical trials.",

author = "Laurent Lam and Soret, {Pierre Antoine} and {Global & ERN Rare-Liver PBC Study Groups} and Sara Lemoinne and Bettina Hansen and Gideon Hirschfield and Aliya Gulamhusein and Montano-Loza, {Aldo J.} and Ellina Lytvyak and Albert Par{\'e}s and Ignasi Olivas and Londono, {Maria Carlota} and Sergio Rodr{\'i}guez-Tajes and Eaton, {John E.} and Osman, {Karim T.} and Christoph Schramm and Marcial Sebode and Lohse, {Ansgar W.} and George Dalekos and Nikolaos Gatselis and Frederik Nevens and Nora Cazzagon and Alessandra Zago and Russo, {Francesco Paolo} and Annarosa Floreani and Nadir Abbas and Palak Trivedi and Douglas Thorburn and Francesca Saffioti and Laszlo Barkai and Davide Roccarina and Vicenza Calvaruso and Anna Fichera and Ad{\`e}le Delamarre and Natalia Sobenko and Villamil, {Alejandra Maria} and Esli Medina-Morales and Alan Bonder and Vilas Patwardhan and Cristina Rigamonti and Marco Carbone and Pietro Invernizzi and Laura Cristoferi and {van der Meer}, Adriaan and {de Veer}, Rozanne and Ehud Zigmond and Eyal Yehezkel and Kremer, {Andreas E.} and Ansgar Deibel and Tony Bruns and Karsten Gro{\ss}e and Aaron Wetten and Jessica Dyson and David Jones and Cynthia Levy and Atsushi Tanaka and J{\'e}r{\^o}me Dumortier and Pageaux, {George Philippe} and {De L{\'e}dinghen}, Victor and Fabrice Carrat and Olivier Chazouill{\`e}res and Christophe Corpechot",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = dec,

doi = "10.1016/j.cgh.2024.06.035",

language = "English",

volume = "22",

pages = "2432--2441.e2",

journal = "Clinical Gastroenterology and Hepatology",

issn = "1542-3565",

number = "12",

}

Lam, L, Soret, PA, Global & ERN Rare-Liver PBC Study Groups, Lemoinne, S, Hansen, B, Hirschfield, G, Gulamhusein, A, Montano-Loza, AJ, Lytvyak, E, Parés, A, Olivas, I, Londono, MC, Rodríguez-Tajes, S, Eaton, JE, Osman, KT, Schramm, C, Sebode, M, Lohse, AW, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, FP, Floreani, A, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Sobenko, N, Villamil, AM, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, van der Meer, A , de Veer, R, Zigmond, E, Yehezkel, E, Kremer, AE, Deibel, A, Bruns, T, Große, K, Wetten, A, Dyson, J, Jones, D, Levy, C, Tanaka, A, Dumortier, J, Pageaux, GP, De Lédinghen, V, Carrat, F, Chazouillères, O & Corpechot, C 2024, 'Dynamics of Liver Stiffness Measurement and Clinical Course of Primary Biliary Cholangitis', Clinical Gastroenterology and Hepatology, vol. 22, no. 12, pp. 2432-2441.e2. https://doi.org/10.1016/j.cgh.2024.06.035

TY - JOUR

T1 - Dynamics of Liver Stiffness Measurement and Clinical Course of Primary Biliary Cholangitis

AU - Lam, Laurent

AU - Soret, Pierre Antoine

AU - Global & ERN Rare-Liver PBC Study Groups

AU - Lemoinne, Sara

AU - Hansen, Bettina

AU - Hirschfield, Gideon

AU - Gulamhusein, Aliya

AU - Montano-Loza, Aldo J.

AU - Lytvyak, Ellina

AU - Parés, Albert

AU - Olivas, Ignasi

AU - Londono, Maria Carlota

AU - Rodríguez-Tajes, Sergio

AU - Eaton, John E.

AU - Osman, Karim T.

AU - Schramm, Christoph

AU - Sebode, Marcial

AU - Lohse, Ansgar W.

AU - Dalekos, George

AU - Gatselis, Nikolaos

AU - Nevens, Frederik

AU - Cazzagon, Nora

AU - Zago, Alessandra

AU - Russo, Francesco Paolo

AU - Floreani, Annarosa

AU - Abbas, Nadir

AU - Trivedi, Palak

AU - Thorburn, Douglas

AU - Saffioti, Francesca

AU - Barkai, Laszlo

AU - Roccarina, Davide

AU - Calvaruso, Vicenza

AU - Fichera, Anna

AU - Delamarre, Adèle

AU - Sobenko, Natalia

AU - Villamil, Alejandra Maria

AU - Medina-Morales, Esli

AU - Bonder, Alan

AU - Patwardhan, Vilas

AU - Rigamonti, Cristina

AU - Carbone, Marco

AU - Invernizzi, Pietro

AU - Cristoferi, Laura

AU - van der Meer, Adriaan

AU - de Veer, Rozanne

AU - Zigmond, Ehud

AU - Yehezkel, Eyal

AU - Kremer, Andreas E.

AU - Deibel, Ansgar

AU - Bruns, Tony

AU - Große, Karsten

AU - Wetten, Aaron

AU - Dyson, Jessica

AU - Jones, David

AU - Levy, Cynthia

AU - Tanaka, Atsushi

AU - Dumortier, Jérôme

AU - Pageaux, George Philippe

AU - De Lédinghen, Victor

AU - Carrat, Fabrice

AU - Chazouillères, Olivier

AU - Corpechot, Christophe

PY - 2024/12

Y1 - 2024/12

N2 - Background & Aims: In primary biliary cholangitis (PBC), static liver stiffness measurement (LSM) has proven prognostic value. However, the added prognostic value of LSM time course in this disease remains uncertain.Methods: We conducted an international retrospective cohort study among patients with PBC treated with ursodeoxycholic acid and followed by vibration-controlled transient elastography between 2003 and 2022. Using joint modeling, the association of LSM trajectory and the incidence of serious clinical events (SCE), defined as cirrhosis complications, liver transplantation, or death, was quantified using the hazard ratio and its confidence interval. Results: A total of 6362 LSMs were performed in 3078 patients (2007 on ursodeoxycholic acid alone; 13% with cirrhosis), in whom 316 SCE occurred over 14,445 person-years (median follow-up, 4.2 years; incidence rate, 21.9 per 1000 person-years). LSM progressed in 59% of patients (mean, 0.39 kPa/year). After adjusting for prognostic factors at baseline, including LSM, any relative change in LSM was associated with a significant variation in SCE risk (P < .001). For example, the adjusted hazard ratios (95% confidence interval) associated with a 20% annual variation in LSM were 2.13 (1.89–2.45) for the increase and 0.40 (0.33–0.46) for the decrease. The association between LSM trajectory and SCE risk persisted regardless of treatment response or duration, when patients with cirrhosis were excluded, and when only death or liver transplantation was considered. Conclusions: Tracking longitudinal changes in LSM using vibration-controlled transient elastography provides valuable insights into PBC prognosis, offering a robust predictive measure for the risk of SCE. LSM could be used as a clinically relevant surrogate end point in PBC clinical trials.

AB - Background & Aims: In primary biliary cholangitis (PBC), static liver stiffness measurement (LSM) has proven prognostic value. However, the added prognostic value of LSM time course in this disease remains uncertain.Methods: We conducted an international retrospective cohort study among patients with PBC treated with ursodeoxycholic acid and followed by vibration-controlled transient elastography between 2003 and 2022. Using joint modeling, the association of LSM trajectory and the incidence of serious clinical events (SCE), defined as cirrhosis complications, liver transplantation, or death, was quantified using the hazard ratio and its confidence interval. Results: A total of 6362 LSMs were performed in 3078 patients (2007 on ursodeoxycholic acid alone; 13% with cirrhosis), in whom 316 SCE occurred over 14,445 person-years (median follow-up, 4.2 years; incidence rate, 21.9 per 1000 person-years). LSM progressed in 59% of patients (mean, 0.39 kPa/year). After adjusting for prognostic factors at baseline, including LSM, any relative change in LSM was associated with a significant variation in SCE risk (P < .001). For example, the adjusted hazard ratios (95% confidence interval) associated with a 20% annual variation in LSM were 2.13 (1.89–2.45) for the increase and 0.40 (0.33–0.46) for the decrease. The association between LSM trajectory and SCE risk persisted regardless of treatment response or duration, when patients with cirrhosis were excluded, and when only death or liver transplantation was considered. Conclusions: Tracking longitudinal changes in LSM using vibration-controlled transient elastography provides valuable insights into PBC prognosis, offering a robust predictive measure for the risk of SCE. LSM could be used as a clinically relevant surrogate end point in PBC clinical trials.

UR - http://www.scopus.com/inward/record.url?scp=85206695807&partnerID=8YFLogxK

U2 - 10.1016/j.cgh.2024.06.035

DO - 10.1016/j.cgh.2024.06.035

M3 - Article

C2 - 39019421

AN - SCOPUS:85206695807

SN - 1542-3565

VL - 22

SP - 2432-2441.e2

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

IS - 12

ER -

Dynamics of Liver Stiffness Measurement and Clinical Course of Primary Biliary Cholangitis

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