Optimising risk stratification in primary biliary cirrhosis: AST/platelet ratio index predicts outcome independent of ursodeoxycholic acid response

PJ Trivedi, T Bruns, A Cheung, KK Li, C Kittler, T Kumagi, H Shah, C Corbett, N Al-Harthy, U Acarsu, C Coltescu, D Tripathi, A Stallmach, J Neuberger, HLA Janssen, GM Hirschfield

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Background & Aims: Outcomes in primary biliary cirrhosis (PBC) can be predicted by biochemical response to ursodeoxycholic acid (UDCA). Such stratification inadequately captures cirrhosis/portal hypertension, recognised factors associated with adverse events. Methods: We evaluated a cohort of PBC patients (n = 386) attending the Liver Unit in Birmingham (derivation cohort), seeking to identify risk-variables associated with transplant-free survival independent of UDCA-response. A validation cohort was provided through well-characterised patients attending the Toronto Center for Liver Diseases (n = 479) and Jena University Hospital (n = 150). Results: On multivariate analysis, factors at diagnosis associated with liver transplant (LT)/death were patient age (HR:1.06; p <0.001), elevated bilirubin (HR: 1.27; p <0.001), early-onset cirrhosis (HR:2.40; p <0.001) and baseline AST/platelet ratio index (APRI) (HR:1.95; p <0.001). At 1-year, UDCA biochemical non-response predicted poorer transplant-free survival, and additional factors (multivariate) associated with adverse outcome were age (HR:1.02; p <0.05) and 1-year APRI (HR:1.15; p <0.001). Obtaining a cut-point from our derivation cohort, APRI >0.54 at baseline was predictive of LT/death (adjusted HR: 2.40; p <0.001), and retained statistical significance when applied at 1-year (APRI-r1, adjusted HR: 2.75; p <0.001) despite controlling for UDCA-response. Across both cohorts, transplant-free survival was poorer for biochemical-responders with an APRI-r1 >0.54 vs. biochemical-responders with a lower APRI-r1 (p <0.01 and p <0.001, respectively); non-responders with high APRI-r1 had the poorest outcomes (p <0.001 and p <0.001). Conclusion: In PBC, elevated APRI is associated with future risk of adverse events, independently and additively of UDCA-response. This cross-centre, robustly validated observation will contribute to ongoing efforts to refine existing risk-stratification tools, as well as direct focus for new therapies in patients with PBC. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)1249-1258
Number of pages10
JournalJournal of Hepatology
Issue number6
Publication statusPublished - 2014

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