Abstract
Background
Several ursodeoxycholic acid (UDCA) treatment response definitions have been introduced
in primary biliary cholangitis (PBC). However, the lack of a gold standard results
in heterogeneity in second-line treatment research and clinical practice.
Aims
This study aimed to explore which UDCA treatment response endpoint serves as the most
accurate predictive model of long-term outcome.
Methods
A systematic review and meta-analysis of UDCA treatment response endpoints (and corresponding
validations) were performed.
Results
Sixteen individual UDCA treatment response endpoints and 96 external validations were
found. Barcelona, Paris-1, Paris-2, Rotterdam, Toronto and GLOBE and UK-PBC Risk Scores
are currently most robustly validated in external populations. The results show that
the continuous models (GLOBE and UK-PBC Risk Scores) serve as the most accurate predictive
models. Besides standard UDCA treatment response endpoints, the alkaline phosphatase
and total bilirubin normalization has been suggested as a new therapeutic target.
Conclusions
The GLOBE and UK-PBC Risk Scores are the most suitable for the real-world allocation
of second-line therapies (obeticholic acid and fibrates). However, in the wake of
the recent findings, alkaline phosphatase and total bilirubin normalization should
be the primary outcome in trial research in PBC.
Key words
Abbreviations:
AASLD (The American Association for the Study of Liver Diseases), ALP (alkaline phosphatase), ALT (alanine aminotransferase), AST (aspartate aminotransferase), AUROC (area under receiver operating characteristic), EASL (The European Association for the Study of the Liver), GGT (gamma-glutamyl transferase), HCC (hepatocellular carcinoma), HR (hazard ratio), kg (kilogram), LT (liver transplantation), MESH (medical subject headings), mg (milligram), OR (odds ratio), PBC (primary biliary cholangitis), PHG (porto-hepatic gradient), PRISMA (The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement), RR (risk ratio), UDCA (ursodeoxycholic acid), ULN (upper limit of normal)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: December 31, 2022
Accepted:
December 19,
2022
Received:
August 26,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
