Patients at risk for HCC should undergo surveillance with ultrasonography, CT scan, or MRI at 6-monthly intervals. Serum-α-fetoprotein (AFP) and protein induced vitamin K absence (PIVKA)-II are the most common markers available to detect HCC. Des gamma carboxyprothrombin (DCP), AFP-L3 (a glycosylated form of AFP which is produced in higher concentration by HCC than normal liver), Golgi membrane protein 73 (GP73), and glypican 3 (GPC3) have been proposed as surveillance tests for HCC. In patients with small tumors or in well-to-moderately differentiated HCC, serum markers rarely elevated. Therefore, there is a need for the development of more sensitive and specific methods that supplement these tumor markers for the early detection of HCC. The present study included 46 patients with HCC, 20 patients with benign hepatic disorders and 20 sex- and age- matched apparent healthy individuals as a control group. The median value of both serum AFP-L3 and AFP-L3/AFP ratio was significantly higher in HCC patients group compared to other groups. There was a significant positive correlation between each of serum AFP, AFP-L3, with each of child classification, tumor size and tumor number, among HCC patients. The best cut-off point for AFP as predictor of HCC was 62 ng/mL, for AFP-L3 as predictor of HCC was 15 ng/mL and for AFP-L3/AFP ratio was 20 %. Combination of AFP and AFP-L3 revealed best cut-off of AFP at 100 ng/mL and AFP-L3 at 4 ng/mL. In conclusion AFP-L3 is a promising marker for diagnosis of HCC especially when combined with AFP.

Keywords: Alfa- Fetoprotein, Hepatocellular Carcinoma, tumor markers.

1.      Filmus J. and Capurro M. (2004): Glypican-3 and alphafetoprotein as diagnostic tests for hepatocellular carcinoma. Mol. Diagn.; 8: 207.

2.      Wei J.J.; Xiao B.M.; Liang T.; Hong Y.S.; Shen J.L.; Guo J.C.; Xiu H.Q. and He PH. (2006): Shanghai China Hepatobiliary Pancr. Dis. Int.; 5:257.

3.      Hong, Y.H.J., Li, H., Chen, S., Liu, Q., Zhang, B., He, X., Wang, Y., Li, H., Li, Y., Zhang, T., Lu, C., Yan, H., Zhang, M., Li, Q., Cao, B., Bai, Z., Wang, J., Zhang, Z., Zhu, S., Zhen, J., Ou, X., Ma, H., JIa, J., You, H., Wang, S., and Huang, J. An analysis of immunoreactive signatures in early stage hepatocellular carcinoma. EBioMedicine. 2015; 2: 438–446

4.      Lin Z.; Liu J. and Luo F. (2006): Serum tumor markers for detection of hepatocellular carcinoma.World J. Gastroenterol.; 12: 1175.

5.      Li D.; Mallory T. and Satamura S. (2001): AFP-L3 a new generation of tumor marker for hepatocellular carcinoma.Clinica Chemica Acta; 313:15-19.

6.      Davi ET.; Du MQ.; Hutchinson WL.; Johnson PJ.; and Williams R. (2001): Differential alpha-fetoproteinlectin binding in hepatocellular carcinoma. Diagnostic utility at low serum levels. Cancer; 67:476–80.

7.      Oka H.; Saito A and Ito K.(2001): Multicenter prospective analysis of newly diagnosed hepatocellular carcinoma with respect to the percentage of Lens culinaris agglutinin-reactive α-fetoprotein.J Gastroen Hepato.;16:1378-1383.

8.      Tada T.; Kumada T and Toyoda. (2005): Relationship between Lens culinaris agglutinin-reactive α-fetoprotein and pathological features of hepatocellular carcinoma. Liver Int.; 25:848-853

9.      Yamashita F.; Tanaka M.; Satomura S and Tanikawa K. (1996): Prognostic significance of Lens culinaris agglutinin A-reactive alpha-fetoprotein in small hepatocellular carcinomas. Gastroenterology; 111:996–1001.

10.  Song B.C.; Chung Y.H.; Kim J.A.; Choi W.B.; Suh D.D.; Pyo S.I.; Shin J.W.; Lee H.C.; Lee Y.S. and Suh D.J. (2002): Transforming growth factor-beta1 as a useful serologic marker of small hepatocellular carcinoma. Cancer; 94:175.

11.  Kumada T.; Nakano S and Takeda I. (1999): Clinical utility of Lens culinaris agglutinin-reactive alpha-fetoprotein in small hepatocellular carcinoma. Special reference to imaging diagnosis. J. Hepatol.; 30:125-130.

12.  Motawa E.; Mohammed S.; Wael M.; Tarek D.; Omar S. and Anwar A. (2006): Enhanced Detection of Hepatocellular Carcinoma. Cancer Control; 12:248-253.

13.  Evi N. Debruyne and Joris R. Delanghe (2008): Diagnosing and monitoring hepatocellular carcinoma with alpha-fetoprotein,new aspects and applications, Clinica. Chimica. Acta. ; 359: 19–26.

14.  Shiraki K.; Takase K.; Tameda Y.; Hamada M.; Kosaka Y and Nakano T. (1996): clinical study of lectin-reactive alpha-fetoprotein as an early indicator of hepatocellular carcinoma in the follow-up of cirrhotic patients. Hepatology; 22:802–7.

15.  Tanwandee T.; Setthasin S.; Charatcharoenwitthaya P.; Chainuvati S.; Leelakusolvong S.; Pausawasdi N.; Srikureja W.; Pongprasobchai S.; Manatsathit S.; Kachintorn U.; Ekpo P and  Senawong S. (2009): Clinical utility of lens culinaris agglutinin-reactive alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: evaluation in a Thai referral population. J Med Assoc Thai.; 92: 49-56.

16.  Apinya Leerapun.;Sri V.; Suravarapu John P.;BidaRaynell J.; Elizabeth L.; Sanders Teresa A.; Mettler Linda M.; Ileana Aderca.; Catherine D.; Moser, David M.; Nagorney.; Nicholas F.; LaRusso.; Piet C.; Narayanan Menon.; Konstantinos N.; and Lewis R. Roberts (2007): The utility of AFP-L3in the diagnosis of HCC. Clin. Gastroenterol. Hepatol. ; 5: 394–267.

17.  Sangiovanni A.; Romeo R.; Iavarone M.; Vavassori S.; Della C.; and Colombo M. (2010): Diagnostic value of lens AFP-L3 and DCP for the diagnosis of HCC. Journal of Hepatology .; 52 : 183–317

18.  Leerapun A.; Louis L.; Tamara S.; David C.; Sara V.B.; Jacques P.; Frederik N.; Chris V.; Jos V. P. and Tania R. (2006): Glypican-3 Expression Distinguishes Small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. The Am. J. Surg. Path.; 30:11. 

Dr Ayman Mohamed Abdou Shamseya

Lecturer, Department of Internal Medicine, Faculty of Medicine, University of Alexandria, Egypt

Address: 21, Elsayed Radwan St, Miami, Alexandria, Egypt

Email: dr.ayman1977@gmail.com, Phone: +201222903176