Alpha-Fetoprotein, Alpha-Fetoprotein-L3, Protein Induced by Vitamin K Absence, Glypican 3 and Its Combinations for Diagnosis of Hepatocellular Carcinoma

Abstract

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.

Evaluation of serum alpha fetoprotein-L3 as an accuracy novel biomarker for the early diagnosis of hepatocellular carcinoma in Egyptian patients

“…This result is close to a study by ( Ibrahim et al, 2018 ) in which AFP-L3 showed sensitivity of 97.5% and specificity of 100%. Our result were even higher than those reported by ( Cerban et al, 2019 ) , where they assessed the diagnostic performance of AFP-L3 in the diagnosis of HCC. The sensitivity of AFP-L3 was 84.75% and specificity was 75.76%.…”

Search for Effective Serum Tumor Markers for Early Diagnosis of Hepatocellular Carcinoma Associated with Hepatitis C

“…For these reasons, the latest research has been directed towards the combined use of two, three, and even four tumor markers with different expression mechanisms in the process of carcinogenesis [27][28][29][30]. There have been described combinations including AFP, AFP-L3, DCP (PIVKA-II), ANXA2, OPN, DKK-1, receptor tyrosine kinase sAxl (AXL), thioredoxin (Trx1) [22,26,27,31,32].…”

“…The combined use of AFP + GPC3 and AFP + OPN has already demonstrated their advantages (AUC is 0.85 and 0.90, respectively) [ 29 , 33 ]. However, MDK and combinations of AFP + MDK, GPC3 + OPN have not been studied yet, therefore, it is a question of future research to investigate effectiveness of using these tumor markers in combination.…”

Update on the applications and limitations of alpha-fetoprotein for hepatocellular carcinoma

“…By using a cut-off value of 23 ng/mL, AFP-L3 had a sensitivity of 97.5% and specificity of 100% in predicting HCC at[ 37 ]. Cerban et al [ 38 ] investigated the diagnostic performance of AFP, AFP-L3, PIVKA-II and GPC-3 for HCC in a cohort including 52 cirrhotic and 101 HCC patients. AFP-L3 at a cut-off point of > 13.5 ng/mL was found to have a higher sensitivity of 84.7%, compared to other biomarkers[ 38 ].…”

“…Cerban et al [ 38 ] investigated the diagnostic performance of AFP, AFP-L3, PIVKA-II and GPC-3 for HCC in a cohort including 52 cirrhotic and 101 HCC patients. AFP-L3 at a cut-off point of > 13.5 ng/mL was found to have a higher sensitivity of 84.7%, compared to other biomarkers[ 38 ]. The sensitivity of AFP-L3 for HCC detection can be affected by its cut-off values, as well as the tumor size and stage[ 40 ].…”