Role of serum glypican-3 in the diagnosis and differentiation of small hepatocellular carcinoma from hepatitis-C virus cirrhosis

Abstract

Background: Serum alpha-fetoprotein (AFP) has insufficient sensitivity and specificity
for detection of hepatocellular carcinoma (HCC). Recently, glypican-3 (GLP-3) was suggested as a new biomarker for the detection HCC.
Objectives: To determine the role of serum GLP-3 levels in the early diagnosis and differentiation of small (3 cm or less in diameter) HCC from liver cirrhosis. Also, to correlate GLP-3 levels to clinico- laboratory data.
Methods: The study included sixty patients; 30 of them with hepatitis C virus (HCV) cirrhosis, and 30 patients with proved HCC. In addition, 20 healthy subjects were included as a control group. Clinical and radiological features (abdominal ultrasonography and/or abdominal triphasic computed tomography) were recorded. Liver function tests, complete blood cell count, and serum AFP were measured. Serum GLP-3 values were determined by an ELISA technique.
Results: Serum levels of GLP-3 were significantly elevated in patients with HCC compared with HCV cirrhosis group (p< 0.001). Also, these levels were significantly elevated in these two patients’ groups versus controls (p<0.001). Also, serum GLP-3 levels with cut-off value of P240 ug/L, had a higher sensitivity (100%) and same specificity (93.3%), than AFP with cut-off value of P200 ng/ ml, for detection of HCC. Moreover, GLP-3 levels showed a higher sensitivity than AFP (50% vs.41.7%), for detection of small HCC. The combined use of both markers (i.e. when either one of the two markers positive) improved the specificity to 88.9%. Regarding unicentric HCC, GLP-3 at cut-off value of 6580 ug/L had better specificity than AFP at cut-off value of 6765 ng/ml (57.1% vs. 42.9%). The combined use of both markers improved the sensitivity and specificity to 82.6% and 71.4%, respectively. 
Conclusion: Serum GLP-3 levels are higher in HCC versus HCV cirrhosis, which can differentiate HCC from liver cirrhosis. Also, serum GLP-3 is highly sensitive and specific for detecting HCC. Moreover, GLP-3 is more sensitive than AFP for the detection of small HCC. Furthermore, a combination of both serum markers yielded an improved specificity and both sensitivity and specificity for the diagnosis of small and unicentric HCC, respectively.

Keywords: Serum tumor marker Alpha-fetoprotein Early hepatocellular carcinoma Diagnosis