Liver and Bile

Hepatology. 2024;79(1):39–48

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?

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. The authors assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains.
Approach and results: They 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% confidence interval [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 months.; 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: Primary biliary cholangitis patients with an adequate response to ursodeoxycholic acid and persistent alkaline phosphatase 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.

DOI: 10.1097/hep.0000000000000529