Maren H Harms1, Willem J Lammers1, Douglas Thorburn2,3, Christophe Corpechot4, Pietro Invernizzi5, Harry L A Janssen6, Pier M Battezzati7, Frederik Nevens8, Keith D Lindor9,10, Annarosa Floreani11, Cyriel Y Ponsioen12, Marlyn J Mayo13, George N Dalekos14, Tony Bruns15, Albert Parés16, Andrew L Mason17, Xavier Verhelst18, Kris V Kowdley19, Jorn C Goet1, Gideon M Hirschfield20, Bettina E Hansen1,6, Henk R van Buuren1. 1. Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands. 2. The Sheila Sherlock Liver Centre, The Royal Free Hospital, London, UK. 3. UCL Institute of Liver and Digestive Health, University College London, London, UK. 4. Centre de Référence des Maladies Inflammatoires des Voies Biliaires, Hôpital Saint-Antoine, APHP, Paris, France. 5. 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. 6. Toronto Centre for Liver disease, Francis Family Liver Clinic, Toronto General Hospital, Toronto, Ontario, Canada. 7. Department of Health Sciences, Università degli Studi di Milano, Milan, Italy. 8. Department of Hepatology, University Hospitals Leuven, KULeuven, Leuven, Belgium. 9. Department Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. 10. College of Health Solutions, Arizona State University, Phoenix, Arizona, USA. 11. Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy. 12. Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. 13. Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA. 14. Department of Medicine and Research Laboratory of Internal Medicine, University of Thessaly, School of Medicine, Larissa, Greece. 15. Department of Gastroenterology, Hepatology and Infectious Disease, Jena University Hospital, Friedrich Schiller University of Jena, Jena, Germany. 16. Liver Unit, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain. 17. Divison of Gastroenterology and Hepatology, University of Alberta, Edmonton, Alberta, Canada. 18. Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium. 19. Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, Washington, USA. 20. NIHR Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK.
Abstract
OBJECTIVES: In this era of near universal ursodeoxycholic acid (UDCA) treatment for primary biliary cholangitis (PBC), progression to cirrhosis still occurs in an important proportion of patients. The aim of this study was to describe the incidence of cirrhosis-associated complications in patients with PBC and assess risk factors and impact on survival. METHODS: Cohorts of UDCA-treated patients from 16 European and North-American liver centers were included. We used Cox proportional hazards assumptions and Kaplan-Meier estimates. RESULTS: During 8.1 years' median follow-up, 278 of 3,224 patients developed ascites, variceal bleeding, and/or encephalopathy (incidence rate of 9.7 cases/1,000 patient years). The overall cumulative incidence was 9.1% after 10 years of follow-up, but decreased over time to 5.8% after the year 2000. Earlier calendar year of diagnosis (P<0.001), high aspartate aminotransferase to platelets ratio index (APRI; P<0.001) and biochemical non-response (P<0.001) were independently associated with future complications. Patients with both biochemical non-response and an APRI >0.54 after 12 months of UDCA had a 10-year complication rate of 37.4%, as compared to 3.2% in biochemical responders with an APRI ≤0.54. The 10-year transplantation-free survival after a complication was 9% (time-dependent hazard ratio 21.5; 20.1-22.8). Prognosis after variceal bleeding has improved over time. CONCLUSIONS: In this large international cohort, up to 15% of UDCA-treated PBC patients developed major non-neoplastic, cirrhosis-associated hepatic complications within 15 years, but cumulative incidence has decreased over time. Biochemical non-response to UDCA and APRI were independent risk factors for these complications. Subsequent long-term outcome after complications is generally poor, but has improved over the past decades.
OBJECTIVES: In this era of near universal ursodeoxycholic acid (UDCA) treatment for primary biliary cholangitis (PBC), progression to cirrhosis still occurs in an important proportion of patients. The aim of this study was to describe the incidence of cirrhosis-associated complications in patients with PBC and assess risk factors and impact on survival. METHODS: Cohorts of UDCA-treated patients from 16 European and North-American liver centers were included. We used Cox proportional hazards assumptions and Kaplan-Meier estimates. RESULTS: During 8.1 years' median follow-up, 278 of 3,224 patients developed ascites, variceal bleeding, and/or encephalopathy (incidence rate of 9.7 cases/1,000 patient years). The overall cumulative incidence was 9.1% after 10 years of follow-up, but decreased over time to 5.8% after the year 2000. Earlier calendar year of diagnosis (P<0.001), high aspartate aminotransferase to platelets ratio index (APRI; P<0.001) and biochemical non-response (P<0.001) were independently associated with future complications. Patients with both biochemical non-response and an APRI >0.54 after 12 months of UDCA had a 10-year complication rate of 37.4%, as compared to 3.2% in biochemical responders with an APRI ≤0.54. The 10-year transplantation-free survival after a complication was 9% (time-dependent hazard ratio 21.5; 20.1-22.8). Prognosis after variceal bleeding has improved over time. CONCLUSIONS: In this large international cohort, up to 15% of UDCA-treated PBC patients developed major non-neoplastic, cirrhosis-associated hepatic complications within 15 years, but cumulative incidence has decreased over time. Biochemical non-response to UDCA and APRI were independent risk factors for these complications. Subsequent long-term outcome after complications is generally poor, but has improved over the past decades.
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