Dynamics of Liver Stiffness Measurement and Clinical Course of Primary Biliary Cholangitis
Laurent Lam, Pierre‐Antoine Soret, Sara Lemoinne, Bettina E. Hansen, Gideon M. Hirschfield, Aliya Gulamhusein, Aldo J. Montaño‐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 Ν. Dalekos, Nikolaos Gatselis, Frederik Nevens, Nora Cazzagon, Alessandra Zago, Francesco Paolo Russo, Annarosa Floreani, Nadir Abbas, Palak Trivedi, Douglas Thorburn, Francesca Saffioti, László Barkai, Davide Roccarina, Vincenza Calvaruso, A. Fichera, Adèle Delamarre, Natalia Sobenko, Alejandra 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, Georges‐Philippe Pageaux, Victor de Lédinghen, Fabrice Carrat, Olivier Chazouillères, Christophe Corpechot
Abstract
Background & AimsIn 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.MethodsWe 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.ResultsA 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.ConclusionsTracking 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. 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. 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. 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. 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.