Major Hepatic Complications in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis: Risk Factors and Time Trends in Incidence and Outcome

Maren H. Harms, Willem J. Lammers, Douglas Thorburn, Christophe Corpechot, Pietro Invernizzi, Harry L. A. Janssen, Pier M. Battezzati, Frederik Nevens, Keith D. Lindor, Annarosa Floreani, Cyriel Y. Ponsioen, Marlyn J. Mayo, George N. Dalekos, Tony Bruns, Albert Parés, Andrew L. Mason, Xavier Verhelst, Kris V. Kowdley, Jorn C. Goet, Gideon M. HirschfieldBettina E. Hansen, Henk R. van Buuren

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Abstract

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. 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. 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. 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
Original languageEnglish
Pages (from-to)254-264
JournalAmerican journal of gastroenterology
Volume113
Issue number2
Early online date2017
DOIs
Publication statusPublished - 2018

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