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?
- Autori: 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, Vincenza; Fichera, Anna; Delamarre, Adèle; 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, Jérôme; Pageaux, Georges-Philippe; de Lédinghen, Victor; Chazouillères, Olivier; Carrat, Fabrice; null, null
- Anno di pubblicazione: 2024
- Tipologia: Articolo in rivista
- OA Link: http://hdl.handle.net/10447/641402
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 (xULN) 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 xULN) 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 xULN, 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.