JHEP Reports (Oct 2024)
Loss of biochemical response at any time worsens outcomes in UDCA-treated patients with primary biliary cholangitis
- Surain B. Roberts,
- Woo Jin Choi,
- Lawrence Worobetz,
- Catherine Vincent,
- Jennifer A. Flemming,
- Angela Cheung,
- Karim Qumosani,
- Mark Swain,
- Dusanka Grbic,
- Hin Hin Ko,
- Kevork M. Peltekian,
- Lusine Abrahamyan,
- Monika Saini,
- Kattleya Tirona,
- Bishoi Aziz,
- Ellina Lytvyak,
- Pietro Invernizzi,
- Cyriel Y. Ponsioen,
- Tony Bruns,
- Nora Cazzagon,
- Keith Lindor,
- George N. Dalekos,
- Nikolaos K. Gatselis,
- Xavier Verhelst,
- Annarosa Floreani,
- Christophe Corpechot,
- Marlyn J. Mayo,
- Cynthia Levy,
- Maria-Carlota Londoño,
- Pier M. Battezzati,
- Albert Pares,
- Frederik Nevens,
- Adriaan van der Meer,
- Kris V. Kowdley,
- Palak J. Trivedi,
- Ana Lleo,
- Douglas Thorburn,
- Marco Carbone,
- Nazia Selzner,
- Aliya F. Gulamhusein,
- Harry LA. Janssen,
- Aldo J. Montano-Loza,
- Andrew L. Mason,
- Gideon M. Hirschfield,
- Bettina E. Hansen
Affiliations
- Surain B. Roberts
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; Li Ka Shing Knowledge Institute, St Michael’s Hospital, Unity Health Toronto, Toronto, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
- Woo Jin Choi
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
- Lawrence Worobetz
- Department of Medicine, University of Saskatchewan, Saskatoon, Canada
- Catherine Vincent
- Département de Médecine, Université de Montréal, Montréal, Canada
- Jennifer A. Flemming
- Department of Medicine, Queen’s University, Kingston, Canada
- Angela Cheung
- Department of Medicine, University of Ottawa, Ottawa, Canada
- Karim Qumosani
- Department of Medicine, Western University, London, Canada
- Mark Swain
- Department of Medicine, University of Calgary, Calgary, Canada
- Dusanka Grbic
- Départment de Médecine, Université de Sherbrooke, Sherbrooke, Canada
- Hin Hin Ko
- Department of Medicine, University of British Columbia, Vancouver, Canada
- Kevork M. Peltekian
- Department of Medicine, Dalhousie University, Halifax, Canada
- Lusine Abrahamyan
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada; Royal Free London National Health Service Foundation Trust, London, United Kingdom
- Monika Saini
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada
- Kattleya Tirona
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada
- Bishoi Aziz
- Department of Medicine, University of Alberta, Edmonton, Canada
- Ellina Lytvyak
- Department of Medicine, University of Alberta, Edmonton, Canada
- Pietro Invernizzi
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy; Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
- Cyriel Y. Ponsioen
- Faculty of Medicine, University of Amsterdam, Amsterdam, the Netherlands
- Tony Bruns
- Department of Gastroenterology and Hepatology, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany
- Nora Cazzagon
- University of Padova, Padova, Italy
- Keith Lindor
- Mayo Clinic, Scottsdale, Arizona, USA
- George N. Dalekos
- European Reference Network on Hepatological Diseases, Barcelona, Spain
- Nikolaos K. Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
- Xavier Verhelst
- Department of Hepatology, Ghent University Hospital, Ghent, Belgium
- Annarosa Floreani
- University of Padova, Padova, Italy; Scientific Institute for Research, Hospitalization and Healthcare, Negrar, Verona, Italy
- Christophe Corpechot
- Reference center for inflammatory biliary diseases and autoimmune hepatitis, French network for rare liver diseases FILFOIE, European reference network RARE-LIVER, Saint-Antoine University Hospital, APHP & Sorbonne University, Paris, France
- Marlyn J. Mayo
- Department of Medicine, Division of Digestive and Liver Disease, University of Texas, Southwestern Medical Center, Dallas, Texas, USA
- Cynthia Levy
- Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, FL, USA
- Maria-Carlota Londoño
- Liver Unit, Hospital Clinic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d’Investigació Pi i Sunyer (FRCB-IDIBAPS), CIBEREHD, European Reference Network on Hepatological Rare Diseases (ERN-Liver), University of Barcelona, Barcelona, Spain
- Pier M. Battezzati
- Università degli Studi di Milano, Milan, Italy
- Albert Pares
- Department of Medicine, Liver Unit, Hospital Clínic, University of Barcelona, The August Pi i Sunyer Biomedical Research Institute, Biomedical Research Networking Center in Hepatic and Digestive Diseases, Barcelona, Spain; European Reference Network on Hepatological Diseases, Barcelona, Spain
- Frederik Nevens
- University Hospital Katholieke Universiteit Leuven, Leuven, Belgium
- Adriaan van der Meer
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
- Kris V. Kowdley
- Liver Institute Northwest, Seattle, Washington, USA
- Palak J. Trivedi
- Liver Unit, University Hospitals Birmingham National Health Service Foundation Trust Queen Elizabeth, Birmingham, UK; National Institute for Health and Care Research (NIHR) Birmingham Liver Biomedical Research Centre, University of Birmingham, College of Medical and Dental Sciences, Birmingham, Birmingham, UK; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; Institute of Applied Health Research, University of Birmingham, Birmingham, UK
- Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
- Douglas Thorburn
- Royal Free London National Health Service Foundation Trust, London, United Kingdom
- Marco Carbone
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy; Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
- Nazia Selzner
- Toronto General Hospital Research Institute, University Health Network, Toronto, Canada
- Aliya F. Gulamhusein
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
- Harry LA. Janssen
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
- Aldo J. Montano-Loza
- Department of Medicine, University of Alberta, Edmonton, Canada
- Andrew L. Mason
- Department of Medicine, University of Alberta, Edmonton, Canada
- Gideon M. Hirschfield
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada; Corresponding authors. Addresses: Department of Epidemiology & Biostatistics, Erasmus MC, Dr. Molenwaterplein 40, Na 2805, 3015 GD Rotterdam, Netherlands. (B. Hansen), or Lily and Terry Horner Chair in Autoimmune Liver Disease Research, Toronto Centre for Liver Disease, Toronto General Hospital, Toronto, Canada. (G. Hirschfield).
- Bettina E. Hansen
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada; Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, the Netherlands; Corresponding authors. Addresses: Department of Epidemiology & Biostatistics, Erasmus MC, Dr. Molenwaterplein 40, Na 2805, 3015 GD Rotterdam, Netherlands. (B. Hansen), or Lily and Terry Horner Chair in Autoimmune Liver Disease Research, Toronto Centre for Liver Disease, Toronto General Hospital, Toronto, Canada. (G. Hirschfield).
- Journal volume & issue
-
Vol. 6,
no. 10
p. 101168
Abstract
Background & Aims: Biochemical response to ursodeoxycholic acid (UDCA) therapy is associated with good prognosis in people living with primary biliary cholangitis (PBC). Biochemical response is typically assessed early in disease and it is not known what proportion of patients lose previously attained biochemical response, nor whether this impacts long-term liver transplant (LT)-free survival. Methods: We identified all UDCA-treated patients with PBC from the Canadian Network for Autoimmune Liver disease with biochemical measurements at 1 year, and evaluated their liver biochemistry over time. Inadequate biochemical response was defined as serum alkaline phosphatase ≥1.67x the upper limit of normal or abnormal serum total bilirubin at 1 year of UDCA therapy and all time points thereafter. Multistate Markov models were used to estimate transition rates between biochemical response states and from each state to LT or death. Results were validated in an external cohort (GLOBAL PBC registry). Results: A total of 823 patients from eight centers were included. Mean age at diagnosis was 53 years, 91% were female, 33% had inadequate biochemical response to UDCA at 1 year (n = 269). Patients who retained initial adequate response had lower rates of LT or death compared to patients who subsequently lost response (relative rate 0.102, 95% CI 0.047-0.223). Patients who regained adequate response had lower rates than patients who did not (0.016, 95% CI 0.001-0.568), and patients who lost response once more (0.010, 95% CI 0.001-0.340). Patients who regained adequate response for a third time also had lower rates than patients who did not (0.151, 95% CI 0.040-0.566). Analyses in the GLOBAL PBC registry (n = 2,237) validated these results. Conclusion: Loss of biochemical response at any time is associated with heightened risks of LT or death in people living with PBC. Achievement of biochemical response is an important goal throughout follow-up, regardless of biochemical response profile early in therapy. Impact and implications:: Early biochemical response to ursodeoxycholic acid is associated with good prognosis in patients with primary biliary cholangitis (PBC). Our work demonstrates that patients with PBC transition between biochemical response states over time, and that these transitions correspond with changes in risk of liver transplantation or death. Clinicians should re-evaluate risk and optimize treatment decisions for patients with PBC throughout follow-up, regardless of early biochemical response to therapy.
