TY - JOUR
T1 - Goals of treatment for improved survival in primary biliary cholangitis
T2 - treatment target should be bilirubin within the normal range and normalization of alkaline phosphatase
AU - Global PBC Study Group
AU - Murillo Perez, Carla F
AU - Harms, Maren H
AU - Lindor, Keith D
AU - van Buuren, Henk R
AU - Hirschfield, Gideon M
AU - Corpechot, Christophe
AU - van der Meer, Adriaan J
AU - Feld, Jordan J
AU - Gulamhusein, Aliya
AU - Lammers, Willem J
AU - Ponsioen, Cyriel Y
AU - Carbone, Marco
AU - Mason, Andrew L
AU - Mayo, Marlyn J
AU - Invernizzi, Pietro
AU - Battezzati, Pier Maria
AU - Floreani, Annarosa
AU - Lleo, Ana
AU - Nevens, Frederik
AU - Kowdley, Kris V
AU - Bruns, Tony
AU - Dalekos, George N
AU - Gatselis, Nikolaos K
AU - Thorburn, Douglas
AU - Trivedi, Palak J
AU - Verhelst, Xavier
AU - Parés, Albert
AU - Janssen, Harry L A
AU - Hansen, Bettina E
PY - 2020/2/20
Y1 - 2020/2/20
N2 - OBJECTIVES: In primary biliary cholangitis (PBC), bilirubin and alkaline phosphatase (ALP) are widely established as independent predictors of prognosis. Current treatment goals do not aim for normalization of surrogate markers because their association with survival has not been defined.METHODS: The patient cohort from the GLOBAL PBC Study Group was used, comprising of long-term follow-up data from European and North American centers. Ursodeoxycholic acid-treated and untreated patients with bilirubin levels ≤1 × upper limit of normal (ULN) at baseline or 1 year were included. The association of normal ALP with transplant-free survival was assessed in a subgroup with ALP ≤1.67 × ULN at 1 year. Optimal thresholds of bilirubin and ALP to predict liver transplantation (LT) or death were evaluated.RESULTS: There were 2,281 patients included in the time zero cohort and 2,555 patients in the 1-year cohort. The bilirubin threshold with the highest ability to predict LT or death at 1 year was 0.6 × ULN (hazard ratio 2.12, 95% CI 1.69-2.66, P < 0.001). The 10-year survival rates of patients with bilirubin ≤0.6 × ULN and >0.6 × ULN were 91.3% and 79.2%, respectively (P < 0.001). The risk for LT or death was stable below the bilirubin levels of 0.6 × ULN, yet increased beyond this threshold. Ursodeoxycholic acid-induced reduction in bilirubin below this threshold was associated with an 11% improvement in 10-year survival. Furthermore, ALP normalization was optimal, with 10-year survival rates of 93.2% in patients with ALP ≤ 1 × ULN and 86.1% in those with ALP 1.0-1.67 × ULN.DISCUSSION: Attaining bilirubin levels ≤0.6 × ULN or normal ALP are associated with the lowest risk for LT or death in patients with PBC. This has important implications for treatment targets.
AB - OBJECTIVES: In primary biliary cholangitis (PBC), bilirubin and alkaline phosphatase (ALP) are widely established as independent predictors of prognosis. Current treatment goals do not aim for normalization of surrogate markers because their association with survival has not been defined.METHODS: The patient cohort from the GLOBAL PBC Study Group was used, comprising of long-term follow-up data from European and North American centers. Ursodeoxycholic acid-treated and untreated patients with bilirubin levels ≤1 × upper limit of normal (ULN) at baseline or 1 year were included. The association of normal ALP with transplant-free survival was assessed in a subgroup with ALP ≤1.67 × ULN at 1 year. Optimal thresholds of bilirubin and ALP to predict liver transplantation (LT) or death were evaluated.RESULTS: There were 2,281 patients included in the time zero cohort and 2,555 patients in the 1-year cohort. The bilirubin threshold with the highest ability to predict LT or death at 1 year was 0.6 × ULN (hazard ratio 2.12, 95% CI 1.69-2.66, P < 0.001). The 10-year survival rates of patients with bilirubin ≤0.6 × ULN and >0.6 × ULN were 91.3% and 79.2%, respectively (P < 0.001). The risk for LT or death was stable below the bilirubin levels of 0.6 × ULN, yet increased beyond this threshold. Ursodeoxycholic acid-induced reduction in bilirubin below this threshold was associated with an 11% improvement in 10-year survival. Furthermore, ALP normalization was optimal, with 10-year survival rates of 93.2% in patients with ALP ≤ 1 × ULN and 86.1% in those with ALP 1.0-1.67 × ULN.DISCUSSION: Attaining bilirubin levels ≤0.6 × ULN or normal ALP are associated with the lowest risk for LT or death in patients with PBC. This has important implications for treatment targets.
UR - http://www.scopus.com/inward/record.url?scp=85087473506&partnerID=8YFLogxK
U2 - 10.14309/ajg.0000000000000557
DO - 10.14309/ajg.0000000000000557
M3 - Article
C2 - 32079858
SN - 0002-9270
VL - 115
SP - 1066
EP - 1074
JO - The American Journal of Gastroenterology
JF - The American Journal of Gastroenterology
IS - 7
ER -