Clinical utility of hepatocellular carcinoma risk scores in chronic hepatitis B

Background: Several risk scores have been recently developed to predict hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. We systematically assessed the performance of the available HCC risk scores. Methods: Literature search was performed to identify all published studies reporting development or external validation of HCC risk scores in CHB patients. Results: Until March 2019, 12 scores were developed in untreated Asian and 7 scores in treated Asian (n = 6) or Caucasian (n = 1) patients. All scores provided significant predictions for HCC development in the derivation and validation cohorts of their original studies (c-statistic: 0.76-0.95) and usually classified patients into low, medium and high HCC risk groups. Eleven independent studies and three studies developing their own scores have validated externally some scores in Asian (GAG-HCC:5, CU-HCC:6, REACH-B:6, REACH-Bm:4, LSM-HCC:3, PAGE-B:5) or Caucasian/mixed origin patients (GAG-HCC:4, CU-HCC:4, REACH-B:4, PAGE-B:2). All scores offered acceptable predictability in almost all independent Asian cohorts (c-statistic: 0.70-0.86), but only PAGE-B and recently modified PAGE-B (mPAGE-B) offered good predictability in all independent Caucasian and/or Asian cohorts. Negative predictive values for 5-year HCC prediction were ≤99% (95%-99%) in most independent cohorts assessing Asian risk scores and 99%-100% in all independent cohorts (Caucasian/mixed origin:2; Asian:3) assessing PAGE-B and/or recently mPAGE-B. Conclusions: Direct comparison of the newest HCC risk scores in independent patient cohorts of different origin remains intriguing, although statistical associations may not be directly transferable to clinical practice. PAGE-B and recently mPAGE-B score seem to offer persistently high predictability for Caucasian and/or Asian treated patients with low HCC risk who require no surveillance.