Surgery, Gastroenterology and Oncology

Introduction: Despite its limitations, alpha-fetoprotein (AFP) is still the most common used serum marker for hepatocellular carcinoma (HCC). Alpha-fetoprotein-L3 (AFP-L3), protein induced by vitamin K absence (PIVKA-II) and Glypican-3 (GPC-3) have been proposed as complementary biomarkers but their role is still controversial.

Aims and Methods: We prospectively included 101 patients with HCC and 52 control patients with liver cirrhosis with the aim to investigate the diagnostic performance of AFP, AFP-L3 PIVKA-II, and GPC-3 as single markers or in combination for HCC diagnosis. To compare the diagnostic value in distinguishing the presence of HCC from chronic nonmalignant liver disease, receiver operating characteristic (ROC) curves were constructed for each marker and for every combination of markers.

Results: When all biomarkers were individually analyzed, AFP-L3 had the highest area under the curve (AUC) (0.84), followed by AFP (0.79), PIVKA-II (0.75) and GPC-3 (0.73) for HCC diagnosis. The best sensitivity (84.7%) was for AFP L3 at a cut-off >13.5ng mL and the best specificity (93.9%) was for AFP at a cut-off >18.9 ng mL. For combinations of two biomarkers, the AUC was highest (0.87) for AFP and AFP-L3. The combination of all four biomarkers resulted in a much better sensitivity (88.1%) and specificity (93.9%) than each of the markers individually (p = 0.01).

Conclusion: AFP-L3 was the most useful single marker for HCC diagnosis, and the combination of AFP, AFP-L3 and PIVKA-II could maximize the diagnostic performance. Efforts to seek novel combination of biomarkers for HCC should be continued.

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