agglutinin-reactive fraction of alpha-fetoprotein improves diagnostic accuracy for hepatocellular carcinoma.

BACKGROUND

Diagnostic accuracy of various tumor markers and their combinations for hepatocellular carcinoma (HCC) was not fully investigated.

AIM

To evaluate the diagnostic accuracy of alpha-fetoprotein (AFP), the agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) and their combination for HCC diagnosis.

METHODS

Patients with newly detected liver mass or elevated serum AFP levels were considered eligible. Serum AFP level, AFP-L3 fraction, and PIVKA-II level were measured at the first visit.

RESULTS

In total, 622 patients were included; 355 patients (57.1%) had chronic liver disease, and 208 (33.4%) had liver cirrhosis. HCC was diagnosed in 160 patients (25.7%). The area under the receiver operating characteristics curves (AUROCs) of the serum AFP, AFP-L3 fraction, AFP-L3, and PIVKA-II levels for the diagnosis of HCC were 0.775, 0.792, 0.814, and 0.834, respectively. A novel diagnostic model was developed by classifying patients in a 1:1 ratio into training and validation sets. Using the binary regression analysis of the training cohort, the AFP, AFP-L3 fraction, and PIVKA-II (ALPs) score was calculated as follows: ALPs score = 3.8 × [serum AFP level (ng/mL) × AFP-L3 fraction (%) × 0.01] + 0.2 × PIVKA-II level (mAU/mL). The AUROC of the ALPs score for diagnosis of HCC was 0.878, significantly higher than that of serum AFP level ( < 0.001), AFP-L3 fraction ( < 0.001), PIVKA-II level ( = 0.036), and AFP-L3 level ( = 0.006). The optimal ALPs score cut-off was 5.3 (sensitivity, 85.0%, specificity 80.1%). The validation cohort showed similar results.

CONCLUSION

The ALPs score calculated using serum AFP level, AFP-L3 fraction, and PIVKA-II level showed improved accuracy in HCC diagnosis.