TY - JOUR
T1 - Fibrosis stage is an independent predictor of outcome in primary biliary cholangitis despite biochemical treatment response
AU - the GLOBAL PBC Study Group
AU - Murillo Perez, Carla F.
AU - Hirschfield, Gideon M.
AU - Corpechot, Christophe
AU - Floreani, Annarosa
AU - Mayo, Marlyn J.
AU - van der Meer, Adriaan
AU - Ponsioen, Cyriel Y.
AU - Lammers, Willem J.
AU - Parés, Albert
AU - Invernizzi, Pietro
AU - Carbone, Marco
AU - Maria Battezzati, Pier
AU - Nevens, Frederik
AU - Kowdley, Kris V.
AU - Thorburn, Douglas
AU - Mason, Andrew L.
AU - Trivedi, Palak J.
AU - Lindor, Keith D.
AU - Bruns, Tony
AU - Dalekos, George N.
AU - Gatselis, Nikolaos K.
AU - Verhelst, Xavier
AU - Janssen, Harry L.A.
AU - Hansen, Bettina E.
AU - Gulamhusein, Aliya
N1 - Funding Information:
This investigator‐initiated study was supported by unrestricted grants from Cymabay Therapeutics Inc., Intercept Pharmaceuticals, and previously from Zambon Nederland BV, and was funded by the Toronto General & Western Hospital Foundation (a not‐for‐profit organization) in Toronto, Canada and the Foundation for Liver and Gastrointestinal Research (a not‐for‐profit foundation) in Rotterdam, the Netherlands. The supporting parties had no influence on the study design, data collection and analyses, writing of the manuscript, or on the decision to submit the manuscript for publication.
Funding Information:
The following authors declared that they have no conflicts of interest: P. Invernizzi, M. Carbone, PM Battezzati, GN Dalekos, N. Gatselis and X. Verhelst. C.F Murillo Perez has served as a speaker for Merck. G.M. Hirschfield reports advisory services for Intercept Pharmaceuticals, Novartis, Cymabay Therapeutics and GlaxoSmithKline Pharmaceuticals. C. Corpechot reports receiving consulting fees from Intercept and Inventiva, grant support from Arrow and Intercept, and fees for teaching from GlaxoSmithKline. A. Floreani reports consulting activities for Intercept Pharmaceuticals. M.J. Mayo reports being on advisory committees or review panels for GSK; grant/research support from Gilead, Cymabay, Intercept, Mallinckrodt, Novartis, Target, GSK and Genfit. A. van der Meer reports speaker fees from Gilead Sciences, AbbVie Pharmaceuticals and Zambon Nederland BV, received an unrestricted grant from Gilead Sciences, and reports travel expenses covered by Dr Falk Pharma. C.Y. Ponsioen has received grant support form Takeda, speaker's fees from Abbvie, Takeda and Dr Falk Pharma, and served as consultant for Takeda. W.J. Lammers reports consulting services for Intercept Pharmaceuticals. A. Parés reports consulting services for Intercept Pharmaceuticals and Novartis Pharma. F. Nevens: Advisory boards for Astellas, Janssen‐Cilag, AbbVie, Gilead, CAF, Intercept, Gore, BMS, Novartis, MSD, Janssen‐Cilag, Promethera Biosciences, Ono Pharma, Durect, Roche, Ferring and Janssen‐Cilag. Research grants from Roche, Ferring and Novartis. K.V. Kowdley reports personal fees from Gilead Sciences, Intercept Pharmaceuticals and Novartis; and grants from Gilead Sciences and Intercept Pharmaceuticals. D. Thorburn reports consulting activities for Intercept Pharmaceuticals. A.L. Mason reports advisory services for Intercept Pharmaceuticals, AbbVie and Novartis; and research funding resources from the Canadian Institutes of Health Research, Canadian Liver Foundation, American Kennel Club, Intercept Pharmaceuticals Inc, AbbVie and Gilead Sciences. P.J. Trivedi receives institutional salary support from the NIHR Birmingham Liver Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. P.J. Trivedi receives research grant funding from the Wellcome trust, the Core Digestive Diseases Charity, Intercept Pharmaceuticals and PSC Support. K.D. Lindor reports that he is an unpaid advisor for Intercept Pharmaceuticals and Shire. T. Bruns has received consulting fees from Intercept Pharmaceuticals and lecture fees and travel expenses from AbbVie, Falk Foundation, Norgine, and Gilead. H.L.A. Janssen reports grants from and consulting work for AbbVie Pharmaceuticals, Bristol‐Myers Squibb, Gilead Sciences, Innogenetics, Merck, Novartis, Roche, Intercept Pharmaceuticals and Janssen. B.E. Hansen reports grants from Intercept Pharmaceuticals, Cymabay Therapeutics, and Zambon Nederland BV and consulting work for Intercept Pharmaceuticals, Cymabay Therapeutics, Albireo AB, and Novartis. A. Gulamhusein reports advisory services for Intercept Pharmaceuticals and Abbvie. Declaration of personal interests:
Publisher Copyright:
© 2019 John Wiley & Sons Ltd
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Background: Fibrosis stage predicts prognosis in patients with chronic liver disease independent of aetiology, although its precise role in risk stratification in patients with primary biliary cholangitis (PBC) remains undefined. Aim: To assess the utility of baseline fibrosis stage in predicting long-term outcomes in the context of biochemical risk stratification. Methods: In a large and globally representative cohort of patients with PBC, liver biopsies performed from 1980 to 2014 were evaluated. The predictive ability of histologic fibrosis stage in addition to treatment response at 1 year (Toronto/Paris-II criteria), as well as non-invasive markers of fibrosis (AST/ALT ratio [AAR], AST to platelet ratio index [APRI], FIB-4), for transplant-free survival was assessed with Cox proportional-hazards models. Results: There were 1828 patients with baseline liver biopsy. Advanced histologic fibrosis (stage 3/4) was an independent predictor of survival in addition to non-invasive measures of fibrosis with the hazard ratios ranging from 1.59 to 2.73 (P <.001). Patients with advanced histologic fibrosis stage had worse survival despite biochemical treatment response, with a 10-year survival of 76.0%-86.6% compared to 94.5%-95.1% depending on the treatment response criteria used. Poor correlations were observed between non-invasive measures of fibrosis and histologic fibrosis stage. Conclusion: Assessment of fibrosis stage grants prognostic value beyond biochemical treatment response at 1 year. This highlights the need to incorporate fibrosis stage in individual risk stratification in patients with PBC, partly to identify those that may derive benefit from novel therapies.
AB - Background: Fibrosis stage predicts prognosis in patients with chronic liver disease independent of aetiology, although its precise role in risk stratification in patients with primary biliary cholangitis (PBC) remains undefined. Aim: To assess the utility of baseline fibrosis stage in predicting long-term outcomes in the context of biochemical risk stratification. Methods: In a large and globally representative cohort of patients with PBC, liver biopsies performed from 1980 to 2014 were evaluated. The predictive ability of histologic fibrosis stage in addition to treatment response at 1 year (Toronto/Paris-II criteria), as well as non-invasive markers of fibrosis (AST/ALT ratio [AAR], AST to platelet ratio index [APRI], FIB-4), for transplant-free survival was assessed with Cox proportional-hazards models. Results: There were 1828 patients with baseline liver biopsy. Advanced histologic fibrosis (stage 3/4) was an independent predictor of survival in addition to non-invasive measures of fibrosis with the hazard ratios ranging from 1.59 to 2.73 (P <.001). Patients with advanced histologic fibrosis stage had worse survival despite biochemical treatment response, with a 10-year survival of 76.0%-86.6% compared to 94.5%-95.1% depending on the treatment response criteria used. Poor correlations were observed between non-invasive measures of fibrosis and histologic fibrosis stage. Conclusion: Assessment of fibrosis stage grants prognostic value beyond biochemical treatment response at 1 year. This highlights the need to incorporate fibrosis stage in individual risk stratification in patients with PBC, partly to identify those that may derive benefit from novel therapies.
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U2 - 10.1111/apt.15533
DO - 10.1111/apt.15533
M3 - Article
C2 - 31621931
AN - SCOPUS:85074085785
SN - 0269-2813
VL - 50
SP - 1127
EP - 1136
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 10
ER -