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Hepatology

Publication date: 2024-01-01
Volume: 79 Pages: 39 - 48
Publisher: Wiley

Author:

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

Keywords:

Science & Technology, Life Sciences & Biomedicine, Gastroenterology & Hepatology, PLACEBO-CONTROLLED TRIAL, BIOCHEMICAL RESPONSE, BEZAFIBRATE, PROGNOSIS, BILIRUBIN, CIRRHOSIS, Humans, Middle Aged, Ursodeoxycholic Acid, Liver Cirrhosis, Biliary, Alkaline Phosphatase, Cholagogues and Choleretics, Retrospective Studies, Treatment Outcome, Global & ERN Rare-Liver PBC Study Groups, 1101 Medical Biochemistry and Metabolomics, 1103 Clinical Sciences, 1107 Immunology, 3202 Clinical sciences, 3204 Immunology

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.