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 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. Hirschfield & 2 others Bettina E. Hansen, Henk R. Van Buuren

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)254-264
Number of pages11
JournalAmerican Journal of Gastroenterology
Volume113
Issue number2
DOIs
StatePublished - Feb 1 2018

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Ursodeoxycholic Acid
Cholangitis
Liver
Incidence
Fibrosis
Hemorrhage
Survival
Kaplan-Meier Estimate
Brain Diseases
Ascites
Liver Cirrhosis
Transplantation

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Major hepatic complications in ursodeoxycholic acid-treated patients with primary biliary cholangitis : Risk factors and time trends in incidence and outcome. / Harms, Maren H.; Lammers, Willem J.; Thorburn, Douglas; Corpechot, Christophe; Invernizzi, Pietro; Janssen, Harry L.A.; Battezzati, Pier M.; Nevens, Frederik; Lindor, Keith; Floreani, Annarosa; Ponsioen, Cyriel Y.; Mayo, Marlyn J.; Dalekos, George N.; Bruns, Tony; Parés, Albert; Mason, Andrew L.; Verhelst, Xavier; Kowdley, Kris V.; Goet, Jorn C.; Hirschfield, Gideon M.; Hansen, Bettina E.; Van Buuren, Henk R.

In: American Journal of Gastroenterology, Vol. 113, No. 2, 01.02.2018, p. 254-264.

Research output: Contribution to journalArticle

Harms, MH, Lammers, WJ, Thorburn, D, Corpechot, C, Invernizzi, P, Janssen, HLA, Battezzati, PM, Nevens, F, Lindor, K, Floreani, A, Ponsioen, CY, Mayo, MJ, Dalekos, GN, Bruns, T, Parés, A, Mason, AL, Verhelst, X, Kowdley, KV, Goet, JC, Hirschfield, GM, Hansen, BE & Van Buuren, HR 2018, 'Major hepatic complications in ursodeoxycholic acid-treated patients with primary biliary cholangitis: Risk factors and time trends in incidence and outcome', American Journal of Gastroenterology, vol. 113, no. 2, pp. 254-264. https://doi.org/10.1038/ajg.2017.440
Harms, Maren H. ; Lammers, Willem J. ; Thorburn, Douglas ; Corpechot, Christophe ; Invernizzi, Pietro ; Janssen, Harry L.A. ; Battezzati, Pier M. ; Nevens, Frederik ; Lindor, Keith ; Floreani, Annarosa ; Ponsioen, Cyriel Y. ; Mayo, Marlyn J. ; Dalekos, George N. ; Bruns, Tony ; Parés, Albert ; Mason, Andrew L. ; Verhelst, Xavier ; Kowdley, Kris V. ; Goet, Jorn C. ; Hirschfield, Gideon M. ; Hansen, Bettina E. ; Van Buuren, Henk R. / Major hepatic complications in ursodeoxycholic acid-treated patients with primary biliary cholangitis : Risk factors and time trends in incidence and outcome. In: American Journal of Gastroenterology. 2018 ; Vol. 113, No. 2. pp. 254-264.
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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.",
author = "Harms, {Maren H.} and Lammers, {Willem J.} and Douglas Thorburn and Christophe Corpechot and Pietro Invernizzi and Janssen, {Harry L.A.} and Battezzati, {Pier M.} and Frederik Nevens and Keith Lindor and Annarosa Floreani and Ponsioen, {Cyriel Y.} and Mayo, {Marlyn J.} and Dalekos, {George N.} and Tony Bruns and Albert Par{\'e}s and Mason, {Andrew L.} and Xavier Verhelst and Kowdley, {Kris V.} and Goet, {Jorn C.} and Hirschfield, {Gideon M.} and Hansen, {Bettina E.} and {Van Buuren}, {Henk R.}",
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T1 - Major hepatic complications in ursodeoxycholic acid-treated patients with primary biliary cholangitis

T2 - Risk factors and time trends in incidence and outcome

AU - Harms, Maren H.

AU - Lammers, Willem J.

AU - Thorburn, Douglas

AU - Corpechot, Christophe

AU - Invernizzi, Pietro

AU - Janssen, Harry L.A.

AU - Battezzati, Pier M.

AU - Nevens, Frederik

AU - Lindor, Keith

AU - Floreani, Annarosa

AU - Ponsioen, Cyriel Y.

AU - Mayo, Marlyn J.

AU - Dalekos, George N.

AU - Bruns, Tony

AU - Parés, Albert

AU - Mason, Andrew L.

AU - Verhelst, Xavier

AU - Kowdley, Kris V.

AU - Goet, Jorn C.

AU - Hirschfield, Gideon M.

AU - Hansen, Bettina E.

AU - Van Buuren, Henk R.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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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