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

TY - JOUR

T1 - Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: To what extent and under what conditions is normal ALP level associated with complication-free survival gain?

AU - Corpechot, Christophe

AU - Lemoinne, Sara

AU - Soret, Pierre-Antoine

AU - Hansen, Bettina

AU - Hirschfield, Gideon

AU - Gulamhusein, Aliya

AU - Montano-Loza, Aldo J

AU - Lytvyak, Ellina

AU - Pares, Albert

AU - Olivas, Ignasi

AU - Eaton, John E

AU - Osman, Karim T

AU - Schramm, Christoph

AU - Sebode, Marcial

AU - Lohse, Ansgar W

AU - Dalekos, George

AU - Gatselis, Nikolaos

AU - Nevens, Frederik

AU - Cazzagon, Nora

AU - Zago, Alessandra

AU - Russo, Francesco Paolo

AU - Floreani, Annarosa

AU - Abbas, Nadir

AU - Trivedi, Palak

AU - Thorburn, Douglas

AU - Saffioti, Francesca

AU - Barkai, Laszlo

AU - Roccarina, Davide

AU - Calvaruso, Vicenza

AU - Fichera, Anna

AU - Delamarre, Adèle

AU - Sobenko, Natalia

AU - Villamil, Alejandra Maria

AU - Medina-Morales, Esli

AU - Bonder, Alan

AU - Patwardhan, Vilas

AU - Rigamonti, Cristina

AU - Carbone, Marco

AU - Invernizzi, Pietro

AU - Cristoferi, Laura

AU - van der Meer, Adriaan

AU - de Veer, Rozanne

AU - Zigmond, Ehud

AU - Yehezkel, Eyal

AU - Kremer, Andreas E

AU - Deibel, Ansgar

AU - Bruns, Tony

AU - Große, Karsten

AU - Wetten, Aaron

AU - Dyson, Jessica Katharine

AU - Jones, David

AU - Dumortier, Jérôme

AU - Pageaux, Georges-Philippe

AU - de Lédinghen, Victor

AU - Chazouillères, Olivier

AU - Carrat, Fabrice

AU - Global & ERN Rare-Liver PBC Study Groups

N1 - Copyright © 2023 American Association for the Study of Liver Diseases.

PY - 2024/1/1

Y1 - 2024/1/1

N2 - 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.

AB - 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.

U2 - 10.1097/HEP.0000000000000529

DO - 10.1097/HEP.0000000000000529

M3 - SCORING: Journal article

C2 - 37399238

VL - 79

SP - 39

EP - 48

JO - HEPATOLOGY

JF - HEPATOLOGY

SN - 0270-9139

IS - 1

ER -