Christophe Corpechot1, Olivier Chazouillères2, Pierre Belnou3, Aldo J Montano-Loza4, Andrew Mason4, Maryam Ebadi4, Dennis Eurich5, Sascha Chopra5, Dietmar Jacob5, Christoph Schramm6, Martina Sterneck6, Tony Bruns7, Philipp Reuken8, Falk Rauchfuss9, Davide Roccarina10, Douglas Thorburn10, Alessio Gerussi10, Palak Trivedi11, Gideon Hirschfield12, Patrick McDowell13, Frederik Nevens14, Olivier Boillot15, Alexie Bosch16, Emiliano Giostra17, Filomena Conti18, Raoul Poupon2, Albert Parés19, Anna Reig19, Maria Francesca Donato20, Federica Malinverno20, Annarosa Floreani21, Francesco Paolo Russo21, Nora Cazzagon21, Xavier Verhelst22, Jorn Goet23, Maren Harms23, Henk van Buuren23, Bettina Hansen24, Fabrice Carrat3, Jérôme Dumortier15. 1. Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, 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. 2. Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, ERN Rare-Liver, Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris; Inserm UMR_S938, Saint-Antoine Research Center, Sorbonne University, Paris, France. 3. Public Health Unit, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris; Pierre Louis Institute of Epidemiology and Public Health, Sorbonne University, Paris, France. 4. Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Canada. 5. Department of General, Visceral and Transplantation Surgery, Charité University Hospital, Berlin, Germany. 6. Department of Medicine I and Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 7. Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany; Department of Internal Medicine IV, Integrated Research and Treatment Center for Sepsis Control and Care, University Hospital, Jena, Germany. 8. Department of Internal Medicine IV, Integrated Research and Treatment Center for Sepsis Control and Care, University Hospital, Jena, Germany. 9. Department of General, Visceral and Vascular Surgery, University Hospital Jena, Jena, Germany. 10. University College London Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom. 11. National Institute for Health Research, Centre for Liver Research, University Hospitals Birmingham, Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom. 12. National Institute for Health Research, Centre for Liver Research, University Hospitals Birmingham, Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom; Department of Gastroenterology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Birmingham, United Kingdom; Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Canada. 13. Department of Gastroenterology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Birmingham, United Kingdom. 14. Division Liver and Biliopancreatic Disorders, University Hospitals KU, Leuven, Belgium. 15. Transplant Hepatology Unit, Edouard Herriot Hospital, Hospices Civils de Lyon, Claude Bernard University, Lyon, France. 16. Transplant Hepatology Unit, Croix Rousse Hospital, Hospices Civils de Lyon, Claude Bernard University, Lyon, France. 17. Hepatology and Gastroenterology Department, Geneva University Hospitals, Geneva, Switzerland. 18. Transplant Hepatology Unit, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris, France. 19. 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. 20. Transplant Hepatology Unit, Division of Gastroenterology and Hepatology, Maggiore Hospital Policlinico, Milan, Italy. 21. Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy. 22. Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium. 23. Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands. 24. Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands; Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Canada.
Abstract
BACKGROUND & AIMS: Recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT) is frequent and can impair graft and patient survival. Ursodeoxycholic acid (UDCA) is the current standard therapy for PBC. We investigated the effect of preventive exposure to UDCA on the incidence and long-term consequences of PBC recurrence after LT. METHODS: We performed a retrospective cohort study in 780 patients transplanted for PBC, between 1983-2017 in 16 centers (9 countries), and followed-up for a median of 11 years. Among them, 190 received preventive UDCA (10-15 mg/kg/day). The primary outcome was histological evidence of PBC recurrence. The secondary outcomes were graft loss, liver-related death, and all-cause death. The association between preventive UDCA and outcomes was quantified using multivariable-adjusted Cox and restricted mean survival time (RMST) models. RESULTS: While recurrence of PBC significantly shortened graft and patient survival, preventive exposure to UDCA was associated with reduced risk of PBC recurrence (adjusted hazard ratio [aHR] 0.41; 95% CI 0.28-0.61; p <0.0001), graft loss (aHR 0.33; 95% CI 0.13-0.82; p <0.05), liver-related death (aHR 0.46; 95% CI 0.22-0.98; p <0.05), and all-cause death (aHR 0.69; 95% CI 0.49-0.96; p <0.05). On RMST analysis, preventive UDCA led to a survival gain of 2.26 years (95% CI 1.28-3.25) over a period of 20 years. Exposure to cyclosporine rather than tacrolimus had a complementary protective effect alongside preventive UDCA, reducing the cumulative incidence of PBC recurrence and all-cause death. CONCLUSIONS: Preventive UDCA after LT for PBC is associated with a reduced risk of disease recurrence, graft loss, and death. A regimen combining cyclosporine and preventive UDCA is associated with the lowest risk of PBC recurrence and mortality. LAY SUMMARY: Recurrence of primary biliary cholangitis after liver transplantation is frequent and can impair graft and patient survival. We performed the largest international study of transplanted patients with primary biliary cholangitis to date. Preventive administration of ursodeoxycholic acid after liver transplantation was associated with reduced risk of disease recurrence, graft loss, liver-related and all-cause mortality. A regimen combining cyclosporine and preventive ursodeoxycholic acid was associated with the best outcomes.
BACKGROUND & AIMS: Recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT) is frequent and can impair graft and patient survival. Ursodeoxycholic acid (UDCA) is the current standard therapy for PBC. We investigated the effect of preventive exposure to UDCA on the incidence and long-term consequences of PBC recurrence after LT. METHODS: We performed a retrospective cohort study in 780 patients transplanted for PBC, between 1983-2017 in 16 centers (9 countries), and followed-up for a median of 11 years. Among them, 190 received preventive UDCA (10-15 mg/kg/day). The primary outcome was histological evidence of PBC recurrence. The secondary outcomes were graft loss, liver-related death, and all-cause death. The association between preventive UDCA and outcomes was quantified using multivariable-adjusted Cox and restricted mean survival time (RMST) models. RESULTS: While recurrence of PBC significantly shortened graft and patient survival, preventive exposure to UDCA was associated with reduced risk of PBC recurrence (adjusted hazard ratio [aHR] 0.41; 95% CI 0.28-0.61; p <0.0001), graft loss (aHR 0.33; 95% CI 0.13-0.82; p <0.05), liver-related death (aHR 0.46; 95% CI 0.22-0.98; p <0.05), and all-cause death (aHR 0.69; 95% CI 0.49-0.96; p <0.05). On RMST analysis, preventive UDCA led to a survival gain of 2.26 years (95% CI 1.28-3.25) over a period of 20 years. Exposure to cyclosporine rather than tacrolimus had a complementary protective effect alongside preventive UDCA, reducing the cumulative incidence of PBC recurrence and all-cause death. CONCLUSIONS: Preventive UDCA after LT for PBC is associated with a reduced risk of disease recurrence, graft loss, and death. A regimen combining cyclosporine and preventive UDCA is associated with the lowest risk of PBC recurrence and mortality. LAY SUMMARY: Recurrence of primary biliary cholangitis after liver transplantation is frequent and can impair graft and patient survival. We performed the largest international study of transplanted patients with primary biliary cholangitis to date. Preventive administration of ursodeoxycholic acid after liver transplantation was associated with reduced risk of disease recurrence, graft loss, liver-related and all-cause mortality. A regimen combining cyclosporine and preventive ursodeoxycholic acid was associated with the best outcomes.
Authors: Carla F Murillo Perez; Tommy Ivanics; Marco P A W Claasen; Peter Yoon; David Wallace; Nazia Selzner; Gideon M Hirschfield; Bettina E Hansen; Gonzalo Sapisochin Journal: Can J Surg Date: 2022-10-12 Impact factor: 2.840
Authors: Maja Mijic; Ivona Saric; Bozena Delija; Milos Lalovac; Nikola Sobocan; Eva Radetic; Dora Martincevic; Tajana Filipec Kanizaj Journal: Can J Gastroenterol Hepatol Date: 2022-07-22