Retrospective Analysis of Diagnostic and Prognostic Value of Serum Glypican-3 in Patients With HCV-Related Cirrhosis With Or Without HCC After Achieving SVR With DAA Treatment

Purpose: Despite achieving sustained virologic response (SVR) after treatment with direct-acting antivirals (DAAs), patients with hepatitis C virus (HCV)-related cirrhosis remain at risk of hepatocellular carcinoma (HCC) development. Glypican-3 (GPC-3) is a heparan sulfate proteoglycan with oncogenic role in HCC. This study aimed to assess the diagnostic and prognostic value of serum GPC-3 in patients with HCV-related cirrhosis who achieved SVR following DAA therapy. Methods: We conducted a retrospective, observational study including 832 patients with HCV-related cirrhosis treated with DAAs between 2014 and 2024. Patients were divided into two cohorts: cohort A (n = 551) without HCC at enrolment and cohort B (n = 281) with established HCC. Serum GPC-3 was measured using a commercially available enzyme immunoassay (CanAg Glypican-3 EIA, Fujirebio Diagnostics AB, Gothenburg, Sweden). Results: We analyzed 832 single serum samples: collected at SVR12 in Cohort A and at HCC diagnosis in Cohort B. GPC-3 levels were significantly higher in patients with HCC compared to those without (95, 50–185 pg/mL vs. 48, 29–79 pg/mL; p < 0.001), with moderate diagnostic accuracy (AUC = 0.711). During follow-up (37, 20–51 months), GPC-3 levels did not predict the development of de novo HCC in cohort A. However, in cohort B, GPC-3 > 150 pg/mL was independently associated with reduced survival (adjusted HR = 1.68, 95% CI 1.03–2.67, p = 0.036). Conclusions: While GPC-3 may be of limited utility for predicting HCC occurrence in patients cured of HCV, it could represent a valuable prognostic factor able to predict survival of patients with established HCC.