Effects of Age and Sex of Response to Ursodeoxycholic Acid and Transplant-free Survival in Patients With Primary Biliary Cholangitis

Global PBC Study Group

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background & Aims: Primary biliary cholangitis (PBC) predominantly affects middle-aged women; there are few data on disease phenotypes and outcomes of PBC in men and younger patients. We investigated whether differences in sex and/or age at the start of ursodeoxycholic acid (UDCA) treatment are associated with response to therapy, based on biochemical markers, or differences in transplant-free survival. Methods: We performed a longitudinal retrospective study of 4355 adults in the Global PBC Study cohort, collected from 17 centers across Europe and North America. Patients received a diagnosis of PBC from 1961 through 2014. We evaluated the effects of sex and age on response to UDCA treatment (based on GLOBE score) and transplant-free survival using logistic regression and Cox regression analyses, respectively. Results: Male patients were older at the start of treatment (58.3±12.1 years vs 54.3±11.6 years for women; P<.0001) and had higher levels of bilirubin and lower circulating platelet counts (P<.0001). Younger patients (45 years or younger) had increased serum levels of transaminases than older patients (older than 45 years). Patients older than 45 years at time of treatment initiation had increased odds of a biochemical response to UDCA therapy, based on GLOBE score, compared to younger patients. The greatest odds of response to UDCA were observed in patients older than 65 years (odds ratio compared to younger patients 45 years or younger, 5.48; 95% CI, 3.92–7.67; P<.0001). Risk of liver transplant or death (compared to a general population matched for age, sex, and birth year) decreased significantly with advancing age: hazard ratio for patients 35 years or younger, 14.59 (95% CI, 9.66–22.02) vs hazard ratio for patients older than 65 years, 1.39 (95% CI, 1.23–1.57) (P<.0001). On multivariable analysis, sex was not independently associated with response or transplant-free survival. Conclusion: In longitudinal analysis of 4355 adults in the Global PBC Study, we associated patient age, but not sex, with response to UDCA treatment and transplant-free survival. Younger age at time of treatment initiation is associated with increased risk of treatment failure, liver transplant, and death.

Original languageEnglish (US)
Pages (from-to)2076-2084.e2
JournalClinical Gastroenterology and Hepatology
Volume17
Issue number10
DOIs
StatePublished - Sep 2019

Fingerprint

Ursodeoxycholic Acid
Cholangitis
Transplants
Survival
Therapeutics
Liver
North America
Transaminases
Treatment Failure
Platelet Count
Bilirubin
Sex Characteristics
Longitudinal Studies
Cohort Studies
Retrospective Studies

Keywords

  • Cholestatic Liver Disease
  • Mortality
  • Risk Stratification
  • Stratified Medicine

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Effects of Age and Sex of Response to Ursodeoxycholic Acid and Transplant-free Survival in Patients With Primary Biliary Cholangitis. / Global PBC Study Group.

In: Clinical Gastroenterology and Hepatology, Vol. 17, No. 10, 09.2019, p. 2076-2084.e2.

Research output: Contribution to journalArticle

@article{1ae5637b6bdc4888b1c7d60b3fc0c26a,
title = "Effects of Age and Sex of Response to Ursodeoxycholic Acid and Transplant-free Survival in Patients With Primary Biliary Cholangitis",
abstract = "Background & Aims: Primary biliary cholangitis (PBC) predominantly affects middle-aged women; there are few data on disease phenotypes and outcomes of PBC in men and younger patients. We investigated whether differences in sex and/or age at the start of ursodeoxycholic acid (UDCA) treatment are associated with response to therapy, based on biochemical markers, or differences in transplant-free survival. Methods: We performed a longitudinal retrospective study of 4355 adults in the Global PBC Study cohort, collected from 17 centers across Europe and North America. Patients received a diagnosis of PBC from 1961 through 2014. We evaluated the effects of sex and age on response to UDCA treatment (based on GLOBE score) and transplant-free survival using logistic regression and Cox regression analyses, respectively. Results: Male patients were older at the start of treatment (58.3±12.1 years vs 54.3±11.6 years for women; P<.0001) and had higher levels of bilirubin and lower circulating platelet counts (P<.0001). Younger patients (45 years or younger) had increased serum levels of transaminases than older patients (older than 45 years). Patients older than 45 years at time of treatment initiation had increased odds of a biochemical response to UDCA therapy, based on GLOBE score, compared to younger patients. The greatest odds of response to UDCA were observed in patients older than 65 years (odds ratio compared to younger patients 45 years or younger, 5.48; 95{\%} CI, 3.92–7.67; P<.0001). Risk of liver transplant or death (compared to a general population matched for age, sex, and birth year) decreased significantly with advancing age: hazard ratio for patients 35 years or younger, 14.59 (95{\%} CI, 9.66–22.02) vs hazard ratio for patients older than 65 years, 1.39 (95{\%} CI, 1.23–1.57) (P<.0001). On multivariable analysis, sex was not independently associated with response or transplant-free survival. Conclusion: In longitudinal analysis of 4355 adults in the Global PBC Study, we associated patient age, but not sex, with response to UDCA treatment and transplant-free survival. Younger age at time of treatment initiation is associated with increased risk of treatment failure, liver transplant, and death.",
keywords = "Cholestatic Liver Disease, Mortality, Risk Stratification, Stratified Medicine",
author = "{Global PBC Study Group} and Cheung, {Angela C.} and Lammers, {Willem J.} and {Murillo Perez}, {Carla F.} and {van Buuren}, {Henk R.} and Aliya Gulamhusein and Trivedi, {Palak J.} and Lazaridis, {Konstantinos N.} and Ponsioen, {Cyriel Y.} and Annarosa Floreani and Hirschfield, {Gideon M.} and Christophe Corpechot and Mayo, {Marlyn J.} and Pietro Invernizzi and Battezzati, {Pier Maria} and Albert Par{\'e}s and Frederik Nevens and Douglas Thorburn and Mason, {Andrew L.} and Marco Carbone and Kowdley, {Kris V.} and Tony Bruns and Dalekos, {George N.} and Gatselis, {Nikolaos K.} and Xavier Verhelst and Lindor, {Keith D.} and Ana Lleo and Raoul Poupon and Janssen, {Harry L.A.} and Hansen, {Bettina E.}",
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TY - JOUR

T1 - Effects of Age and Sex of Response to Ursodeoxycholic Acid and Transplant-free Survival in Patients With Primary Biliary Cholangitis

AU - Global PBC Study Group

AU - Cheung, Angela C.

AU - Lammers, Willem J.

AU - Murillo Perez, Carla F.

AU - van Buuren, Henk R.

AU - Gulamhusein, Aliya

AU - Trivedi, Palak J.

AU - Lazaridis, Konstantinos N.

AU - Ponsioen, Cyriel Y.

AU - Floreani, Annarosa

AU - Hirschfield, Gideon M.

AU - Corpechot, Christophe

AU - Mayo, Marlyn J.

AU - Invernizzi, Pietro

AU - Battezzati, Pier Maria

AU - Parés, Albert

AU - Nevens, Frederik

AU - Thorburn, Douglas

AU - Mason, Andrew L.

AU - Carbone, Marco

AU - Kowdley, Kris V.

AU - Bruns, Tony

AU - Dalekos, George N.

AU - Gatselis, Nikolaos K.

AU - Verhelst, Xavier

AU - Lindor, Keith D.

AU - Lleo, Ana

AU - Poupon, Raoul

AU - Janssen, Harry L.A.

AU - Hansen, Bettina E.

PY - 2019/9

Y1 - 2019/9

N2 - Background & Aims: Primary biliary cholangitis (PBC) predominantly affects middle-aged women; there are few data on disease phenotypes and outcomes of PBC in men and younger patients. We investigated whether differences in sex and/or age at the start of ursodeoxycholic acid (UDCA) treatment are associated with response to therapy, based on biochemical markers, or differences in transplant-free survival. Methods: We performed a longitudinal retrospective study of 4355 adults in the Global PBC Study cohort, collected from 17 centers across Europe and North America. Patients received a diagnosis of PBC from 1961 through 2014. We evaluated the effects of sex and age on response to UDCA treatment (based on GLOBE score) and transplant-free survival using logistic regression and Cox regression analyses, respectively. Results: Male patients were older at the start of treatment (58.3±12.1 years vs 54.3±11.6 years for women; P<.0001) and had higher levels of bilirubin and lower circulating platelet counts (P<.0001). Younger patients (45 years or younger) had increased serum levels of transaminases than older patients (older than 45 years). Patients older than 45 years at time of treatment initiation had increased odds of a biochemical response to UDCA therapy, based on GLOBE score, compared to younger patients. The greatest odds of response to UDCA were observed in patients older than 65 years (odds ratio compared to younger patients 45 years or younger, 5.48; 95% CI, 3.92–7.67; P<.0001). Risk of liver transplant or death (compared to a general population matched for age, sex, and birth year) decreased significantly with advancing age: hazard ratio for patients 35 years or younger, 14.59 (95% CI, 9.66–22.02) vs hazard ratio for patients older than 65 years, 1.39 (95% CI, 1.23–1.57) (P<.0001). On multivariable analysis, sex was not independently associated with response or transplant-free survival. Conclusion: In longitudinal analysis of 4355 adults in the Global PBC Study, we associated patient age, but not sex, with response to UDCA treatment and transplant-free survival. Younger age at time of treatment initiation is associated with increased risk of treatment failure, liver transplant, and death.

AB - Background & Aims: Primary biliary cholangitis (PBC) predominantly affects middle-aged women; there are few data on disease phenotypes and outcomes of PBC in men and younger patients. We investigated whether differences in sex and/or age at the start of ursodeoxycholic acid (UDCA) treatment are associated with response to therapy, based on biochemical markers, or differences in transplant-free survival. Methods: We performed a longitudinal retrospective study of 4355 adults in the Global PBC Study cohort, collected from 17 centers across Europe and North America. Patients received a diagnosis of PBC from 1961 through 2014. We evaluated the effects of sex and age on response to UDCA treatment (based on GLOBE score) and transplant-free survival using logistic regression and Cox regression analyses, respectively. Results: Male patients were older at the start of treatment (58.3±12.1 years vs 54.3±11.6 years for women; P<.0001) and had higher levels of bilirubin and lower circulating platelet counts (P<.0001). Younger patients (45 years or younger) had increased serum levels of transaminases than older patients (older than 45 years). Patients older than 45 years at time of treatment initiation had increased odds of a biochemical response to UDCA therapy, based on GLOBE score, compared to younger patients. The greatest odds of response to UDCA were observed in patients older than 65 years (odds ratio compared to younger patients 45 years or younger, 5.48; 95% CI, 3.92–7.67; P<.0001). Risk of liver transplant or death (compared to a general population matched for age, sex, and birth year) decreased significantly with advancing age: hazard ratio for patients 35 years or younger, 14.59 (95% CI, 9.66–22.02) vs hazard ratio for patients older than 65 years, 1.39 (95% CI, 1.23–1.57) (P<.0001). On multivariable analysis, sex was not independently associated with response or transplant-free survival. Conclusion: In longitudinal analysis of 4355 adults in the Global PBC Study, we associated patient age, but not sex, with response to UDCA treatment and transplant-free survival. Younger age at time of treatment initiation is associated with increased risk of treatment failure, liver transplant, and death.

KW - Cholestatic Liver Disease

KW - Mortality

KW - Risk Stratification

KW - Stratified Medicine

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U2 - 10.1016/j.cgh.2018.12.028

DO - 10.1016/j.cgh.2018.12.028

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JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

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