Author information

¹Sorbonne University, Inserm, Pierre Louis Institute of Epidemiology and Public Health, Paris; Public Health Unit, Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris, European Reference Network on Hepatological Diseases (ERN Rare-Liver), France.

²Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, European Reference Network on Hepatological Diseases (ERN Rare-Liver), Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris; Inserm UMR_S938, Saint-Antoine Research Center, Sorbonne University, Paris, France.

³Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Canada; Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, the Netherlands.

⁴Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Canada.

⁵Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Canada.

⁶Division of Preventive Medicine, University of Alberta, Edmonton, Alberta, Canada.

⁷Liver Unit, Hospital Clínic Barcelona, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, University of Barcelona, European Reference Network on Hepatological Diseases (ERN Rare-Liver), Barcelona, Spain.

⁸Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, USA.

⁹Department of Medicine I and Martin Zeitz Center for Rare Diseases, European Reference Network on Hepatological Diseases (ERN Rare-Liver), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

¹⁰Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN Rare-Liver), General University Hospital, Larissa, Greece.

¹¹Division of Hepatology and Liver Transplantation, European Reference Network on Hepatological Diseases (ERN Rare-Liver), University Hospitals KU, Leuven, Belgium.

¹²Department of Surgery, Oncology and Gastroenterology, European Reference Network on Hepatological Diseases (ERN Rare-Liver), University of Padova, Padova, Italy.

¹³Liver Unit, University Hospitals Birmingham National Health Service Foundation Trust Queen Elizabeth, Birmingham, United Kingdom.

¹⁴National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre (BRC), Institute of Immunology and Immunotherapy, Centre for Liver and Gastrointestinal Research, University of Birmingham, Birmingham B15 2TT, United Kingdom.

¹⁵University College London Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom.

¹⁶Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy.

¹⁷Department of Hepatology, University Hospitals of Bordeaux, Pessac, France.

¹⁸Department of Hepatology & Liver Transplantation, Italian Hospital of Buenos Aires, Argentina.

¹⁹Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, USA.

²⁰Department of Translational Medicine, Università del Piemonte Orientale and Division of Internal Medicine, AOU Maggiore della Carità, Novara, Italy.

²¹Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

²²Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.

²³The Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

²⁴Department of Gastroenterology and Hepatology, University Hospital Zürich, University of Zürich, Zürich, Switzerland.

²⁵Department of Medicine III, University Hospital RWTH Aachen, European Reference Network on Hepatological Diseases (ERN Rare-Liver), Aachen, Germany.

²⁶Department of Hepatology and Liver Transplantation, Newcastle upon Tyne Hospitals NHS Foundation Trust, Translational and Clinical Research Institute, Newcastle University, United Kingdom.

²⁷Division of Digestive Health and Liver Diseases, Schiff Center for Liver Diseases, Miami University, United States.

²⁸Department of Medicine, Teikyo University, Japan.

²⁹Department of Gastroenterology and Hepatology, Edouard Herriot Hospital, Hospices Civils de Lyon, Claude Bernard University, Lyon, France.

³⁰Department of Hepatology and Liver Transplantation, University Hospital, Montpellier, France.

³¹Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, European Reference Network on Hepatological Diseases (ERN Rare-Liver), Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris; Inserm UMR_S938, Saint-Antoine Research Center, Sorbonne University, Paris, France. Electronic address: christophe.corpechot@aphp.fr.

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 PBC patients treated with ursodeoxycholic acid (UDCA) and followed by vibration-controlled transient elastography (VCTE) 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 (LT) or death, was quantified using the hazard ratio (HR) and its confidence interval (CI).

Results: A total of 6,362 LSMs were performed in 3,078 patients (2,007 on UDCA 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 1,000 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<0.001). For example, the adjusted HRs (95% CI) 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 LT was considered.

Conclusions: Tracking longitudinal changes in LSM using VCTE 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 endpoint in PBC clinical trials.