Loss of biochemical response at any time worsens outcomes in UDCA-treated patients with primary biliary cholangitis

Surain B Roberts,Surain B Roberts,Surain B Roberts,Woo Jin Choi,Lawrence Worobetz,Catherine Vincent,Jennifer A Flemming,Angela Cheung,Karim Qumosani,Mark Swain,Dusanka Grbic,Hin Hin Ko,Kevork M Peltekian,Lusine Abrahamyan,Lusine Abrahamyan,Monika Saini,Kattleya Tirona,Bishoi Aziz,Ellina Lytvyak,Pietro Invernizzi,Pietro Invernizzi,Cyriel Y Ponsioen,Tony Bruns,Nora Cazzagon,Keith Lindor,George N Dalekos,Nikolaos K Gatselis,Xavier Verhelst,Annarosa Floreani,Annarosa Floreani,Christophe Corpechot,Marlyn J Mayo,Cynthia Levy,Maria-Carlota Londoño,Pier M Battezzati,Albert Pares,Albert Pares,Frederik Nevens,Adriaan Van Der Meer,Kris V Kowdley,Palak J Trivedi,Palak J Trivedi,Palak J Trivedi,Palak J Trivedi,Ana Lleo,Ana Lleo,Douglas Thorburn,Marco Carbone,Marco Carbone,Nazia Selzner,Aliya F Gulamhusein,Aliya F Gulamhusein,Harry La Janssen,Harry La Janssen,Aldo J Montano-Loza,Andrew L Mason,Gideon M Hirschfield,Gideon M Hirschfield,Bettina E Hansen,Bettina E Hansen,Bettina E Hansen

doi:10.1016/j.jhepr.2024.101168

Abstract

Background & AimsBiochemical response to ursodeoxycholic acid (UDCA) therapy is associated with good prognosis in people living with primary biliary cholangitis (PBC). Biochemical response is typically assessed early in disease and it is not known what proportion of patients lose previously attained biochemical response, nor whether this impacts long-term liver-transplant-free survival. MethodsWe identified all UDCA-treated patients with PBC from the Canadian Network for Autoimmune Liver disease with biochemical measurements at one year, and evaluated their liver biochemistry over time. Inadequate biochemical response was defined as serum alkaline phosphatase ≥ 1.67xULN or abnormal serum total bilirubin at one year of UDCA therapy and all time points thereafter. Multistate Markov models were used to estimate transition rates between biochemical response states and from each state to liver transplantation (LT) or death. Results were validated in an external cohort (GLOBAL PBC registry). ResultsA total of 823 patients from 8 centers were included. Mean age at diagnosis was 53 years, 91% were female, 33% had inadequate biochemical response to UDCA at one year (n = 269). Patients who retained initial adequate response had lower rates of LT or death compared to patients who subsequently lost response (relative rate 0.102, 95%CI 0.047-0.223). Patients who regained adequate response had lower rates than patients who did not (0.016, 0.001-0.568), and patients who lost response once more (0.010, 0.001-0.340). Patients who regained adequate response for a third time also had lower rates than patients who did not (0.151, 0.040-0.566). Analyses in the GLOBAL PBC registry (n=2237) validated these results. ConclusionLoss of biochemical response at any time is associated with heightened risks of liver transplantation or death in people living with PBC. Achievement of biochemical response is an important goal throughout follow-up, regardless of biochemical response profile early in therapy.

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