12nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 040 12, Kosice, Slovakia.
22nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 040 12, Kosice, Slovakia. Electronic address: firstname.lastname@example.org.
3Intelligent Information Systems Laboratory, Technical University of Kosice, Bozeny Nemcovej 32, 04201 Kosice, Slovakia.
4Division of Gastroenterology and Centre for Autoimmune Liver Disease, University of Milano-Bicocca, Piazza dell'Ateneo Nuovo, 1, 20126 Milano, Italy.
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.