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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?

Lookup NU author(s): Dr Aaron Wetten, Dr Jess Dyson, Professor David Jones


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

Publication metadata

Author(s): Corpechot C, Lemoinne S, Soret P-A, Hansen B, Hirschfield G, Gulamhusein A, Montano-Loza AJ, Lytvyak E, Pares A, Olivas I, Eaton JE, Osman KT, Schramm C, Sebode M, Lohse AW, Dalekos G, Gatselis N, Nevens F, Cazzagon N, Zago A, Russo FP, Floreani A, Abbas N, Trivedi P, Thorburn D, Saffioti F, Barkai L, Roccarina D, Calvaruso V, Fichera A, Delamarre A, Sobenko N, Villamil AM, Medina-Morales E, Bonder A, Patwardhan V, Rigamonti C, Carbone M, Invernizzi P, Cristoferi L, van der Meer A, de Veer R, Zigmond E, Yehezkel E, Kremer AE, Deibel A, Bruns T, Grosse K, Wetten A, Dyson JK, Jones D, Dumortier J, Pageaux G-P, de Ledinghen V, Chazouilleres O, Carrat F

Publication type: Article

Publication status: Published

Journal: Hepatology

Year: 2024

Volume: 79

Issue: 1

Pages: 39-48

Print publication date: 01/01/2024

Acceptance date: 02/04/2018

ISSN (print): 0270-9139

ISSN (electronic): 1527-3350

Publisher: Wolters Kluwer Health


DOI: 10.1097/HEP.0000000000000529

PubMed id: 37399238


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