The differential diagnosis between hepatocellular carcinoma (HCC) and benign chronic liver disease (CLD)
is sometimes difficult and new biochemical markers for HCC are required. Glypican-3 (GPC3) has been reported to
be a novel tumor marker for the diagnosis of HCC. In this study, we evaluated GPC3 level by a sandwich ELISA
method in sera of 10 healthy subjects, 39 patients with CLD and 60 patients with HCC. Our data showed that 47%
of HCC patients had elevated levels of serum GPC3 with values ranging from 35.5 to 6,547.9 ng/mL, whereas the
marker was undetectable in the other groups. In most cases of HCC, elevated GPC3 values did not correlate with
elevated alpha-fetoprotein (AFP) values. The simultaneous determination of GPC3 and AFP (at a cutoff value of
20 ng/mL) significantly increased the sensitivity of the diagnosis to 80%. In conclusion, serum GPC3 elevation is
highly specific for HCC. The combined use of serum GPC3 and AFP may significantly increase the sensitivity for
differentiating HCC from CLD.