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Purpose <p>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.</p> Methods <p>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 (<i>n</i> = 551) without HCC at enrolment and cohort B (<i>n</i> = 281) with established HCC. Serum GPC-3 was measured using a commercially available enzyme immunoassay (CanAg Glypican-3 EIA, Fujirebio Diagnostics AB, Gothenburg, Sweden).</p> Results <p>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&#xa0;pg/mL vs. 48, 29–79&#xa0;pg/mL; <i>p</i> &lt; 0.001), with moderate diagnostic accuracy (AUC = 0.711). During follow-up (37, 20–51&#xa0;months), GPC-3 levels did not predict the development of de novo HCC in cohort A. However, in cohort B, GPC-3 &gt; 150&#xa0;pg/mL was independently associated with reduced survival (adjusted HR = 1.68, 95% CI 1.03–2.67, <i>p</i> = 0.036).</p> Conclusions <p>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.</p>

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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

  • 期刊论文

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  • 发表日期：

    2026年1月9日

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  • Gian Paolo Caviglia,
  • Marta Guariglia,
  • Silvia Gaia,
  • Yulia Troshina,
  • Emanuela Rolle,
  • Francesca Saba,
  • Eleonora Dileo,
  • Patrizia Carucci,
  • Alessia Ciancio

摘要

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.