HCC Biomarkers

AFP-L3 and DCP

AFP-L3 Test

FDA Cleared and CMS Reimbursed

AFP-L3, a fucosylated alpha-fetoprotein, has been widely used in Japan as a serum marker for early recognition of hepatocellular carcinoma (HCC) and as prognostic indicator after treatment in clinical practice. AFP-L3 test is FDA cleared for HCC risk assessment and is available at major reference labs in the United States. AFP-L3 is reported as AFP-L3%, the ratio of AFP-L3 to total AFP (Alpha-fetoprotein).

Serum alpha-fetoprotein (AFP) is currently the most widely used serologic tumor marker for HCC diagnosis [1]. However, serum AFP can fluctuate in patients with chronic liver diseases without HCC. AFP therefore lacks the clinical accuracy to be an effective HCC management tool [2]. In addition, patients with persistently elevated AFP are usually diagnosed at advanced stages of HCC at which point the treatment becomes increasingly difficult. Consequently, the American Association for the Study of the Liver Diseases (AASLD) currently does not recommend the use of AFP as an independent screening tool for early detection of HCC [3].

AFP-L3 Molecule

Many studies have shown that AFP-L3, the glycosylated variant of AFP with an additional α1-6 fucose residue, is a better marker for early detection and for prognosis for HCC [4-11]. A recent study has shown that diagnosis of HCC based solely on an elevated or rising AFP (>500 ng/mL) resulted in a high false-positive rate [12]. On the other hand, AFP-L3% greater than 10% had a specificity of 92.5% versus 61.6% for an AFP level of 10 ng/mL [13].

Moreover, according to Dr. Apinya Leerapun at Mayo Clinic, patients with total AFP values of 10-200 ng/mL present a "diagnostic dilemma". Dr. Leerapun and Mayo Clinic colleagues showed that in patients with total AFP in the 10-200 ng/mL range, AFP-L3% greater than 10% had 71% sensitivity and 63% specificity. The diagnostic specificity approached 100% when they used the higher cut-off of 35% AFP-L3% [6]. Using the high specificity of AFP-L3, several studies report detection of HCC 3 to 18 months before diagnosis by imaging techniques [10,11].

Unlike total AFP, AFP-L3 correlates with the staging of HCC and with patient outcome. Several studies correlating the prognosis of patients with HCC and AFP-L3 demonstrated that AFP-L3 is associated with reduced liver function, poorer differentiation, and biologically malignant characteristics [4,7,14]. A five year post-treatment follow-up study has shown that AFP-L3-negative patients with small liver cancer (<2 cm in maximum diameter) have a longer cumulative survival rate, and lower recurrence rate after treatment [8].

AFP-L3 is also useful in assessment of HCC treatment. Tateishi et al. reported that AFP-L3 positivity after ablation was the strongest predictor of recurrence and that the presence of AFP-L3 postablation is a strong indication of residual cancer that cannot be detected with imaging techniques [9]. AFP-L3 therefore, strongly demonstrates to be a better HCC marker than total AFP in HCC management.

References

  1. Clin Gastroenterol Hepatol. 2006; 4:252-261.
  2. Hepatol 1998; 27:273-278.
  3. Hepatology 2005, 42:1208-1236.
  4. J Gastroenterol Hepatol 2001; 16(12):1378-83.
  5. Clin Chim Acta 2001 Nov; 313(1-2):15-9.
  6. ClinGastroenterol Hepatol 2007; 5:394-402.
  7. Int J Biol Markers 2001; 16(2):105-111.
  8. Am J Gastroenterol 1999; 94(10):3028-33.
  9. Hepatol 2006 Dec; 44(6):1518-1527.
  10. N Engl J Med 1993; 1802-1806.
  11. Hepatol 1985; 22:802-807.
  12. Liver Transplantation 2006; 12:1519-1522.