Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis

Maren H. Harms, Henk R. van Buuren, Christophe Corpechot, Douglas Thorburn, Harry L.A. Janssen, Keith D. Lindor, Gideon M. Hirschfield, Albert Parés, Annarosa Floreani, Marlyn J Mayo, Pietro Invernizzi, Pier Maria Battezzati, Frederik Nevens, Cyriel Y. Ponsioen, Andrew L. Mason, Kris V. Kowdley, Willem J. Lammers, Bettina E. Hansen, Adriaan J. van der Meer

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
JournalJournal of Hepatology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Ursodeoxycholic Acid
Cholangitis
Transplants
Survival
Liver
Therapeutics
Standard of Care

Keywords

  • Cholestasis
  • Clinical trials
  • Mortality
  • Patient management
  • Treatment
  • UDCA, transplantation

ASJC Scopus subject areas

  • Hepatology

Cite this

Harms, M. H., van Buuren, H. R., Corpechot, C., Thorburn, D., Janssen, H. L. A., Lindor, K. D., ... van der Meer, A. J. (2019). Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis. Journal of Hepatology. https://doi.org/10.1016/j.jhep.2019.04.001

Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis. / Harms, Maren H.; van Buuren, Henk R.; Corpechot, Christophe; Thorburn, Douglas; Janssen, Harry L.A.; Lindor, Keith D.; Hirschfield, Gideon M.; Parés, Albert; Floreani, Annarosa; Mayo, Marlyn J; Invernizzi, Pietro; Battezzati, Pier Maria; Nevens, Frederik; Ponsioen, Cyriel Y.; Mason, Andrew L.; Kowdley, Kris V.; Lammers, Willem J.; Hansen, Bettina E.; van der Meer, Adriaan J.

In: Journal of Hepatology, 01.01.2019.

Research output: Contribution to journalArticle

Harms, MH, van Buuren, HR, Corpechot, C, Thorburn, D, Janssen, HLA, Lindor, KD, Hirschfield, GM, Parés, A, Floreani, A, Mayo, MJ, Invernizzi, P, Battezzati, PM, Nevens, F, Ponsioen, CY, Mason, AL, Kowdley, KV, Lammers, WJ, Hansen, BE & van der Meer, AJ 2019, 'Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis', Journal of Hepatology. https://doi.org/10.1016/j.jhep.2019.04.001
Harms, Maren H. ; van Buuren, Henk R. ; Corpechot, Christophe ; Thorburn, Douglas ; Janssen, Harry L.A. ; Lindor, Keith D. ; Hirschfield, Gideon M. ; Parés, Albert ; Floreani, Annarosa ; Mayo, Marlyn J ; Invernizzi, Pietro ; Battezzati, Pier Maria ; Nevens, Frederik ; Ponsioen, Cyriel Y. ; Mason, Andrew L. ; Kowdley, Kris V. ; Lammers, Willem J. ; Hansen, Bettina E. ; van der Meer, Adriaan J. / Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis. In: Journal of Hepatology. 2019.
@article{c4a82899a4a947bc8f278d0b858427b9,
title = "Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis",
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.",
keywords = "Cholestasis, Clinical trials, Mortality, Patient management, Treatment, UDCA, transplantation",
author = "Harms, {Maren H.} and {van Buuren}, {Henk R.} and Christophe Corpechot and Douglas Thorburn and Janssen, {Harry L.A.} and Lindor, {Keith D.} and Hirschfield, {Gideon M.} and Albert Par{\'e}s and Annarosa Floreani and Mayo, {Marlyn J} and Pietro Invernizzi and Battezzati, {Pier Maria} and Frederik Nevens and Ponsioen, {Cyriel Y.} and Mason, {Andrew L.} and Kowdley, {Kris V.} and Lammers, {Willem J.} and Hansen, {Bettina E.} and {van der Meer}, {Adriaan J.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.jhep.2019.04.001",
language = "English (US)",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier",

}

TY - JOUR

T1 - Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis

AU - Harms, Maren H.

AU - van Buuren, Henk R.

AU - Corpechot, Christophe

AU - Thorburn, Douglas

AU - Janssen, Harry L.A.

AU - Lindor, Keith D.

AU - Hirschfield, Gideon M.

AU - Parés, Albert

AU - Floreani, Annarosa

AU - Mayo, Marlyn J

AU - Invernizzi, Pietro

AU - Battezzati, Pier Maria

AU - Nevens, Frederik

AU - Ponsioen, Cyriel Y.

AU - Mason, Andrew L.

AU - Kowdley, Kris V.

AU - Lammers, Willem J.

AU - Hansen, Bettina E.

AU - van der Meer, Adriaan J.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Cholestasis

KW - Clinical trials

KW - Mortality

KW - Patient management

KW - Treatment

KW - UDCA, transplantation

UR - http://www.scopus.com/inward/record.url?scp=85066080497&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85066080497&partnerID=8YFLogxK

U2 - 10.1016/j.jhep.2019.04.001

DO - 10.1016/j.jhep.2019.04.001

M3 - Article

C2 - 30980847

AN - SCOPUS:85066080497

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

ER -