Liver Cancer-Specific Isoform of Serine Protease Inhibitor Kazal for the Detection of Hepatocellular Carcinoma: Results from a Pilot Study in Patients with Dysmetabolic Liver Disease.

Reliable non-invasive biomarkers for the surveillance of patients at risk of hepatocellular carcinoma (HCC) development represent an unmet medical need. Recently, the liver-cancer-specific isoform of serine protease inhibitor Kazal (LC-SPIK) has been proposed as a valuable biomarker for the detection of HCC in patients with chronic liver disease of viral etiology. In the present study, we assessed the diagnostic accuracy of LC-SPIK, alone or in combination with standard serologic biomarkers (i.e., alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II, PIVKA-II), for the detection of HCC among patients with dysmetabolic liver disease. A total of 120 patients with non-alcoholic fatty liver disease (NAFLD), including 62 patients with a diagnosis of HCC and 58 with cirrhosis but without tumor, were retrospectively analyzed. The serum levels of LC-SPIK were measured by enzyme-linked immunosorbent assay (ImCare Biotech, Doylestown, PA). The serum LC-SPIK values were significantly different between patients with HCC (24.3, 17.6−39.8 ng/mL) and those with cirrhosis but without tumor (11.7, 8.7−18.2 ng/mL) (p < 0.001). By receiver operating characteristic curve analysis, we observed an area under the curve (AUC) of 0.841 for the detection of HCC; the combination with PIVKA-II further increased the accuracy to AUC = 0.926 (cross-validation). The promising results observed in the present pilot study foster additional research to investigate the usefulness of LC-SPIK for the stratification of the risk of HCC development in patients with NAFLD and advanced liver disease.