Serum GP88 as a predictive biomarker for hepatocellular carcinoma in patients with viral hepatitis C after direct-acting antiviral agents

Abstract

Background: Progranulin (GP88) is an 88-kDa glycoprotein growth factor with important biological effects in tumorigenesis and tumor survival. We investigated the usefulness of measuring serum GP88 (sGP88) levels as a predictive biomarker for hepatocellular carcinoma (HCC) in patients with viral hepatitis C after treatment with direct-acting antiviral (DAA) agents. Methods: We measured the sGP88 levels by using a sandwich enzyme-linked immunoassay from 67 healthy control subjects and 29 patients (20 patients who did not develop HCC and 9 patients who developed HCC after treatment) with viral hepatitis C after treatment with asunaprevir and daclatasvir. Results: The sGP88 levels of patients with chronic hepatitis C prior to antiviral treatment were significantly higher than those of healthy control subjects. After antiviral treatment, the sGP88 levels of patients who eventually developed HCC were significantly higher than those who did not develop HCC. The changes in the sGP88 levels before and after treatment in patients who developed HCC were significantly lower than those in patients who did not develop HCC. The cumulative incidence of HCC was significantly higher in either patients with high sGP88 levels after treatment or those with small changes of sGP88 levels pre- and post-treatment. Conclusions: Sustained high levels of sGP88 in patients treated with DAA agents are correlated with the risk of developing HCC.