Interpretation

Alpha-fetoprotein (AFP)-L3 results of 10% or more are associated with a 7-fold increased risk of developing hepatocellular carcinoma (HCC). Patients with AFP-L3 levels of 10% or more should be monitored more intensely for evidence of hepatocellular carcinoma according to current practice guidelines.

Total serum AFP results above 200 ng/mL are highly suggestive of a diagnosis of HCC. In patients with liver disease, a total serum AFP level above 200 ng/mL is near 100% predictive of HCC. With lower total AFP levels, there is an increased likelihood that chronic liver disease, rather than HCC, is responsible for the AFP elevation.

Based on a retrospective study at Mayo Clinic, for patients with total AFP levels 200 ng/mL or less, AFP-L3 specificity approaches 100% for HCC when its percentage exceeds 35% of the total AFP.(4)

AFP concentrations over 100,000 ng/mL have been reported in normal newborns, and the values rapidly decline in the first 6 years of life.

Des-gamma-carboxy prothrombin:

In patients with an elevated des-gamma-carboxy prothrombin (DCP) result (≥7.5 ng/mL), the risk of developing HCC is 36.5% (95% CI 23.5%-49.6%). The risk of developing HCC with a negative DCP result (<7.5 ng/mL) is 7.6% (95% CI 4.4%-10.8%).

Gender, Age, AFP-L3, AFP, DCP (GALAD) Score:

Higher GALAD model scores correlate with increased risk of HCC. The area under the curve (AUC) of a receiver operating characteristic curve of the GALAD score was 0.95 for all HCC detection, and 0.92 for the detection of early-stage HCC. Additionally, the AUC of the GALAD score (0.95) was higher than that of ultrasound alone for all HCC detection (AUC of 0.82, P <0.01).

The sensitivity and specificity performance characteristics of the GALAD score for HCC will be influenced by the selected GALAD score cut-off. For example, at an optimal AUC cutoff of -0.76, the GALAD score had 91% sensitivity and 85% specificity for HCC detection. At a more specific GALAD score cutoff of 0.88, the observed sensitivity was 80% for HCC detection with an observed specificity of 97%.

The GALAD model was developed and validated in patient cohorts with a prevalence of HCC ranging from 35% to 49%. The performance of the model may be altered in populations with different HCC prevalence. In addition, the clinical performance of the GALAD score varies by etiology of HCC and therefore may be different in different regions of the world.