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

J Hepatol. 2014 Jun;60(6):1249-58. doi: 10.1016/j.jhep.2014.01.029. Epub 2014 Feb 15.


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.

Keywords: Autoimmune liver disease; Cholestasis; Liver transplantation; Outcome prediction; Survival; Ursodeoxycholic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aspartate Aminotransferases / blood*
  • Cholagogues and Choleretics / therapeutic use*
  • Databases, Factual
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Liver Cirrhosis, Biliary* / drug therapy
  • Liver Cirrhosis, Biliary* / mortality
  • Liver Cirrhosis, Biliary* / surgery
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Platelet Count*
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Risk Factors
  • Ursodeoxycholic Acid / therapeutic use*


  • Cholagogues and Choleretics
  • Ursodeoxycholic Acid
  • Aspartate Aminotransferases