Diagnostic performance of GAAD, PIVKA-II and AFP in hepatocellular carcinoma, chronic liver disease and healthy population: evidence from a Malaysian cohort

Abstract Background The aim of the current study was to evaluate the diagnostic performances of GAAD score, PIVKA-II and alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance in HCC, chronic liver disease (CLD) and healthy controls (HC) subjects from the northeastern Peninsular Malaysia. Methods This was a single-center cross-sectional study. The GAAD value was calculated using the Elecsysâ GAAD calculator. Serum PIVKA-II and AFP levels were measured using the Elecsysâ electrochemiluminescence immunoassay method. Diagnostic performance of these tests were evaluated based on area under the curve (AUC), optimal cutoff levels, sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). Results Of the 128 enrolled subjects,99 were included (33 HCC, 33 CLD, and 33 HC). GAAD score, PIVKA-II, and AFP levels were significantly higher in patients with HCC than in those with CLD and HC (all p < 0.05). For differentiating HCC from CLD, GAAD at a cutoff of 2.57 demonstrated the highest Se (81.8%) and Sp (72.7%), with an AUC of 0.873 (95% CI 0.791–0.955). PIVKA-II at a cut-off of 28.4 ng/mL showed Se and Sp of 75.8% and 69.7%, respectively, with an AUC of 0.842 (95% CI 0.748–0.936). AFP at a cutoff of 20 ng/mL demonstrated lower Se (51.5%) but higher Sp (90.9%), with an AUC of 0.834 (95% CI 0.730–0.938). For differentiating HCC from HC, GAAD and PIVKA-II achieved 100% Sp and PPV, whereas AFP maintained 100% Sp but lower Se (51.52%). Overall, GAAD exhibited the best balance of sensitivity and specificity for HCC detection, while PIVKA-II provided complementary diagnostic value due to its high specificity. Conclusion The GAAD score demonstrated superior diagnostic performance compared with both PIVKA-II and AFP in differentiating HCC from CLD and HC subjects, supporting its potential utility in HCC surveillance. In addition, PIVKA-II showed better diagnostic performance than AFP.