Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: To what extent and under what conditions is normal alkaline phosphatase level associated with complication-free survival gain?

Christophe Corpechot*, Sara Lemoinne, Pierre Antoine Soret, Bettina Hansen, Gideon Hirschfield, Aliya Gulamhusein, Aldo J. Montano-Loza, Ellina Lytvyak, Albert Pares, Ignasi Olivas, John E. Eaton, Karim T. Osman, Christoph Schramm, Marcial Sebode, Ansgar W. Lohse, George Dalekos, Nikolaos Gatselis, Frederik Nevens, Nora Cazzagon, Alessandra ZagoFrancesco Paolo Russo, Annarosa Floreani, Nadir Abbas, Palak Trivedi, Douglas Thorburn, Francesca Saffioti, Laszlo Barkai, Davide Roccarina, Vicenza Calvaruso, Anna Fichera, Adele Delamarre, Natalia Sobenko, Alejandra Maria Villamil, Esli Medina-Morales, Alan Bonder, Vilas Patwardhan, Cristina Rigamonti, Marco Carbone, Pietro Invernizzi, Laura Cristoferi, Adriaan Van Der Meer, Rozanne De Veer, Ehud Zigmond, Eyal Yehezkel, Andreas E. Kremer, Ansgar Deibel, Tony Bruns, Karsten Große, Aaron Wetten, Jessica Katharine Dyson, David Jones, Jérôme Dumortier, Georges Philippe Pageaux, Victor De Lédinghen, Olivier Chazouillères, Fabrice Carrat

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Aims: Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (×ULN) after 12-month UDCA. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains. Approach and Results: We performed a retrospective cohort study of 1047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation, or death was assessed using adjusted restricted mean survival time (RMST) analysis. The overall incidence rate of events was 17.0 (95% CI: 13.7-21.1) per 1000 out of 4763.2 patient-years. On the whole population, normal serum ALP values (but not normal gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST); or total bilirubin < 0.6 ×ULN) were associated with a significant absolute complication-free survival gain at 10 years (mean 7.6 months, 95% CI: 2.7 - 12.6 mo.; p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10 kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95% CI: 45.7-59.9, p < 0.001) when these 2 conditions were met. Conclusions: PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 ×ULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients.

Original languageEnglish
Pages (from-to)39-48
Number of pages10
JournalHepatology
Volume79
Issue number1
DOIs
StatePublished - Jan 2024
Externally publishedYes

Funding

FundersFunder number
Gilead Sciences

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