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?
Corpechot, Christophe Lemoinne, Sara Soret, Pierre-Antoine Hansen, Bettina Hirschfield, Gideon Gulamhusein, Aliya Montano-Loza, Aldo J Lytvyak, Ellina Pares, Albert Olivas, Ignasi
Corpechot, Christophe
Lemoinne, Sara
Soret, Pierre-Antoine
Hansen, Bettina
Hirschfield, Gideon
Gulamhusein, Aliya
Montano-Loza, Aldo J
Lytvyak, Ellina
Pares, Albert
Olivas, Ignasi
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2023-07-03
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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 1,047 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 analysis. The overall incidence rate of events was 17.0 (95%CI 13.7 - 21.1) per 1,000 out of 4,763.2 patient-years. On the whole population, normal serum ALP values (but not normal GGT, ALT, or AST; or total bilirubin < 0.6 xULN) were associated with an overall absolute complication-free survival gain at 10 years of 7.6 months (95%CI 2.7 - 12.6, 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 two 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.
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Corpechot C, Lemoinne S, Soret PA, 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 GP, de Lédinghen V, Chazouillères O, Carrat F; Global & ERN Rare-Liver PBC Study Groups. 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? Hepatology. 2024 Jan 1;79(1):39-48. doi: 10.1097/HEP.0000000000000529. Epub 2023 Jul 3.
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Article