Maren H Harms1, Henk R van Buuren1, Christophe Corpechot2, Douglas Thorburn3, Harry L A Janssen4, Keith D Lindor5, Gideon M Hirschfield6, Albert Parés7, Annarosa Floreani8, Marlyn J Mayo9, Pietro Invernizzi10, Pier Maria Battezzati11, Frederik Nevens12, Cyriel Y Ponsioen13, Andrew L Mason14, Kris V Kowdley15, Willem J Lammers1, Bettina E Hansen16, Adriaan J van der Meer17. 1. Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands. 2. Centre de Référence des Maladies Inflammatoires des Voies Biliaires, Hôpital Saint-Antoine, APHP, Paris, France. 3. The Sheila Sherlock Liver Centre, and UCL Institute of Liver and Digestive Health, The Royal Free Hospital, London, United Kingdom. 4. Toronto Centre for Liver Disease, Francis Family Liver Clinic, Toronto General Hospital, Toronto, ON, Canada. 5. Arizona State University, College of Health Solutions, Phoenix, AZ, USA; Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA. 6. Toronto Centre for Liver Disease, Francis Family Liver Clinic, Toronto General Hospital, Toronto, ON, Canada; Birmingham NIHR Biomedical Research Centre, and Centre for Liver Research, University of Birmingham, Birmingham, UK. 7. Liver Unit, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain. 8. Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy. 9. Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA. 10. Division of Gastroenterology and Program for Autoimmune Liver Diseases, International Center for Digestive Health, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy. 11. Department of Health Sciences, Università degli Studi di Milano, Milan, Italy. 12. Department of Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. 13. Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. 14. Division of Gastroenterology and Hepatology, University of Alberta, Edmonton, AB, Canada. 15. Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, WA, USA. 16. Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands; Toronto Centre for Liver Disease, Francis Family Liver Clinic, Toronto General Hospital, Toronto, ON, Canada. 17. Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: a.vandermeer@erasmusmc.nl.
Abstract
BACKGROUND & AIMS: The clinical efficacy of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) remains subject to debate as definitive randomized controlled trials are lacking. We aimed to determine whether UDCA prolongs liver transplant (LT)-free survival in patients with PBC. METHODS: This international cohort study included patients from the Global PBC Study Group database, originating from 8 countries in Europe and North America. Both UDCA-treated and untreated patients were included. LT and death were assessed as a combined endpoint through Cox regression analyses, with inverse probability treatment weighting (IPTW). RESULTS: In the 3,902 patients included, the mean (SD) age was 54.3 (11.9) years, 3,552 patients (94.0%) were female, 3,529 patients (90.4%) were treated with UDCA and 373 patients (9.6%) were not treated. The median (interquartile range) follow-up was 7.8 (4.1-12.1) years. In total, 721 UDCA-treated patients and 145 untreated patients died or underwent LT. After IPTW, the 10-year cumulative LT-free survival was 79.7% (95% CI 78.1-81.2) among UDCA-treated patients and 60.7% (95% CI 58.2-63.4) among untreated patients (p <0.001). UDCA was associated with a statistically significant reduced risk of LT or death (hazard ratio 0.46, 95% CI 0.40-0.52; p <0.001). The hazard ratio remained statistically significant in all stages of disease. Patients classified as inadequate biochemical responders after 1 year of UDCA had a lower risk of LT or death than patients who were not treated (adjusted hazard ratio 0.56; 95% CI 0.45-0.69; p <0.001). CONCLUSION: The use of UDCA improves LT-free survival among patients with PBC, regardless of the disease stage and the observed biochemical response. These findings support UDCA as the current universal standard of care in PBC. LAY SUMMARY: In this international multicenter study of 3,902 patients with primary biliary cholangitis, we found that treatment with ursodeoxycholic acid is associated with prolonged liver transplant-free survival. This association was significant, irrespective of sex, age, or disease stage. The survival benefit remained statistically significant in patients with an incomplete biochemical response to ursodeoxycholic acid therapy.
BACKGROUND & AIMS: The clinical efficacy of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) remains subject to debate as definitive randomized controlled trials are lacking. We aimed to determine whether UDCA prolongs liver transplant (LT)-free survival in patients with PBC. METHODS: This international cohort study included patients from the Global PBC Study Group database, originating from 8 countries in Europe and North America. Both UDCA-treated and untreated patients were included. LT and death were assessed as a combined endpoint through Cox regression analyses, with inverse probability treatment weighting (IPTW). RESULTS: In the 3,902 patients included, the mean (SD) age was 54.3 (11.9) years, 3,552 patients (94.0%) were female, 3,529 patients (90.4%) were treated with UDCA and 373 patients (9.6%) were not treated. The median (interquartile range) follow-up was 7.8 (4.1-12.1) years. In total, 721 UDCA-treated patients and 145 untreated patientsdied or underwent LT. After IPTW, the 10-year cumulative LT-free survival was 79.7% (95% CI 78.1-81.2) among UDCA-treated patients and 60.7% (95% CI 58.2-63.4) among untreated patients (p <0.001). UDCA was associated with a statistically significant reduced risk of LT or death (hazard ratio 0.46, 95% CI 0.40-0.52; p <0.001). The hazard ratio remained statistically significant in all stages of disease. Patients classified as inadequate biochemical responders after 1 year of UDCA had a lower risk of LT or death than patients who were not treated (adjusted hazard ratio 0.56; 95% CI 0.45-0.69; p <0.001). CONCLUSION: The use of UDCA improves LT-free survival among patients with PBC, regardless of the disease stage and the observed biochemical response. These findings support UDCA as the current universal standard of care in PBC. LAY SUMMARY: In this international multicenter study of 3,902 patients with primary biliary cholangitis, we found that treatment with ursodeoxycholic acid is associated with prolonged liver transplant-free survival. This association was significant, irrespective of sex, age, or disease stage. The survival benefit remained statistically significant in patients with an incomplete biochemical response to ursodeoxycholic acid therapy.
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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Authors: Jakub Gazda; Martin Janicko; Sylvia Drazilova; Ivica Grgurevic; Tajana Filipec Kanizaj; Tomas Koller; Beatrica Bodorovska; Maja Mijic; Ivana Mikolasevic; Ivana Knezevic Stromar; Branislav Kucinsky; Matej Gazda; Peter Jarcuska Journal: Can J Gastroenterol Hepatol Date: 2021-06-22