TY - JOUR
T1 - Loss of biochemical response at any time worsens outcomes in UDCA-treated patients with primary biliary cholangitis
AU - Roberts, Surain B.
AU - Choi, Woo Jin
AU - Worobetz, Lawrence
AU - Vincent, Catherine
AU - Flemming, Jennifer A.
AU - Cheung, Angela
AU - Qumosani, Karim
AU - Swain, Mark
AU - Grbic, Dusanka
AU - Ko, Hin Hin
AU - Peltekian, Kevork M.
AU - Abrahamyan, Lusine
AU - Saini, Monika
AU - Tirona, Kattleya
AU - Aziz, Bishoi
AU - Lytvyak, Ellina
AU - Invernizzi, Pietro
AU - Ponsioen, Cyriel Y.
AU - Bruns, Tony
AU - Cazzagon, Nora
AU - Lindor, Keith
AU - Dalekos, George N.
AU - Gatselis, Nikolaos K.
AU - Verhelst, Xavier
AU - Floreani, Annarosa
AU - Corpechot, Christophe
AU - Mayo, Marlyn J.
AU - Levy, Cynthia
AU - Londoño, Maria-Carlota
AU - Battezzati, Pier M.
AU - Pares, Albert
AU - Nevens, Frederik
AU - van der Meer, Adriaan
AU - Kowdley, Kris V.
AU - Trivedi, Palak J.
AU - Lleo, Ana
AU - Thorburn, Douglas
AU - Carbone, Marco
AU - Selzner, Nazia
AU - Gulamhusein, Aliya F.
AU - Janssen, Harry LA.
AU - Montano-Loza, Aldo J.
AU - Mason, Andrew L.
AU - Hirschfield, Gideon M.
AU - Hansen, Bettina E.
PY - 2024/7/8
Y1 - 2024/7/8
N2 - Background & Aims: Biochemical 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.Methods: We 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).Results: A 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.Conclusion: Loss 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.
AB - Background & Aims: Biochemical 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.Methods: We 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).Results: A 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.Conclusion: Loss 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.
KW - UDCA
KW - liver transplantation
KW - prognostication
KW - alkaline phosphatase
KW - total bilirubin
U2 - 10.1016/j.jhepr.2024.101168
DO - 10.1016/j.jhepr.2024.101168
M3 - Article
SN - 2589-5559
JO - JHEP Reports
JF - JHEP Reports
M1 - 101168
ER -