Aldo J Montano-Loza1, Bettina E Hansen2, Christophe Corpechot3, Davide Roccarina4, Douglas Thorburn4, Palak Trivedi5, Gideon Hirschfield6, Patrick McDowell7, Raoul Poupon3, Jerome Dumortier8, Alexie Bosch8, Emiliano Giostria9, Filomena Conti10, Albert Parés11, Anna Reig11, Annarosa Floreani12, Francesco Paolo Russo12, Jorn C Goet2, Maren H Harms2, Henk van Buuren2, Natalie Van den Ende13, Frederik Nevens13, Xavier Verhelst14, Maria Francesca Donato15, Federica Malinverno15, Maryam Ebadi16, Andrew L Mason16. 1. Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada. Electronic address: montanol@ualberta.ca. 2. Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands. 3. Reference Center for Inflammatory Biliary Diseases, Saint-Antoine Hospital, Paris, France. 4. University College London Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom. 5. National Institute for Health Research, Centre for Liver Research, University Hospitals Birmingham, Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom. 6. 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. 7. Department of Gastroenterology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Birmingham, United Kingdom. 8. Liver Transplant Unit, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France. 9. Hepatology and Gastroenterology Department, University Hospitals of Geneva, Geneva, Switzerland. 10. Liver Transplant Unit, Pitié-Salpêtrière Hôpital, Paris France. 11. 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. 12. Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy. 13. Division Liver and Biliopancreatic Disorders, Leuven, Belgium. 14. Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium. 15. Transplant Hepatology Unit, Division of Gastroenterology and Hepatology, Maggiore Hospital Policlinico, Milan, Italy. 16. Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
Abstract
BACKGROUND & AIMS: Primary biliary cholangitis (PBC) frequently recurs after liver transplantation. We evaluated risk factors associated with recurrence of PBC and its effects on patient and graft survival in a multicenter, international cohort (the Global PBC Study Group). METHODS: We collected demographic and clinical data from 785 patients (89% female) with PBC who underwent liver transplantation (mean age, 54 ± 9 years) from February 1983 through June 2016, among 13 centers in North America and Europe. Results from biochemical tests performed within 12 months of liver transplantation were analyzed to determine whether markers of cholestasis could identify patients with recurrence of PBC (based on histologic analysis). Patients were followed for a median 6.9 years (interquartile range, 6.1-7.9 years). RESULTS: PBC recurred in 22% of patients after 5 years and 36% after 10 years. Age at diagnosis <50 years (hazard ratio [HR], 1.79; 95% CI, 1.36-2.36; P < .001), age at liver transplantation <60 years (HR, 1.39; 95% CI, 1.02-1.90; P = .04), use of tacrolimus (HR, 2.31; 95% CI, 1.72-3.10; P < .001), and biochemical markers of severe cholestasis (bilirubin ≥100 μmol or alkaline phosphatase >3-fold the upper limit of normal) at 6 months after liver transplantation (HR, 1.79; 95% CI, 1.16-2.76; P = .008) were associated with higher risk of PBC recurrence, whereas use of cyclosporine reduced risk of PBC recurrence (HR, 0.62; 95% CI, 0.46-0.82; P = .001). In multivariable Cox regression with time-dependent covariate, recurrence of PBC significantly associated with graft loss (HR, 2.01; 95% CI, 1.16-3.51; P = .01) and death (HR, 1.72; 95% CI, 1.11-2.65; P = .02). CONCLUSIONS: Younger age at the time of diagnosis with PBC or at liver transplantation, tacrolimus use, and biochemical markers of cholestasis after liver transplantation are associated with PBC recurrence. PBC recurrence reduces odds of graft and patient survival. Strategies are needed to prevent PBC recurrence or reduce its negative effects.
BACKGROUND & AIMS:Primary biliary cholangitis (PBC) frequently recurs after liver transplantation. We evaluated risk factors associated with recurrence of PBC and its effects on patient and graft survival in a multicenter, international cohort (the Global PBC Study Group). METHODS: We collected demographic and clinical data from 785 patients (89% female) with PBC who underwent liver transplantation (mean age, 54 ± 9 years) from February 1983 through June 2016, among 13 centers in North America and Europe. Results from biochemical tests performed within 12 months of liver transplantation were analyzed to determine whether markers of cholestasis could identify patients with recurrence of PBC (based on histologic analysis). Patients were followed for a median 6.9 years (interquartile range, 6.1-7.9 years). RESULTS:PBC recurred in 22% of patients after 5 years and 36% after 10 years. Age at diagnosis <50 years (hazard ratio [HR], 1.79; 95% CI, 1.36-2.36; P < .001), age at liver transplantation <60 years (HR, 1.39; 95% CI, 1.02-1.90; P = .04), use of tacrolimus (HR, 2.31; 95% CI, 1.72-3.10; P < .001), and biochemical markers of severe cholestasis (bilirubin ≥100 μmol or alkaline phosphatase >3-fold the upper limit of normal) at 6 months after liver transplantation (HR, 1.79; 95% CI, 1.16-2.76; P = .008) were associated with higher risk of PBC recurrence, whereas use of cyclosporine reduced risk of PBC recurrence (HR, 0.62; 95% CI, 0.46-0.82; P = .001). In multivariable Cox regression with time-dependent covariate, recurrence of PBC significantly associated with graft loss (HR, 2.01; 95% CI, 1.16-3.51; P = .01) and death (HR, 1.72; 95% CI, 1.11-2.65; P = .02). CONCLUSIONS: Younger age at the time of diagnosis with PBC or at liver transplantation, tacrolimus use, and biochemical markers of cholestasis after liver transplantation are associated with PBC recurrence. PBC recurrence reduces odds of graft and patient survival. Strategies are needed to prevent PBC recurrence or reduce its negative effects.
Authors: Alena Laschtowitz; Rozanne C de Veer; Adriaan J Van der Meer; Christoph Schramm Journal: United European Gastroenterol J Date: 2020-04-16 Impact factor: 4.623
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