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Treatment response to ursodeoxycholic acid in primary biliary cholangitis: A systematic review and meta-analysis

Published:December 31, 2022DOI:https://doi.org/10.1016/j.dld.2022.12.010

      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)
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