Serum Angiopoietin-2 Levels Predict the Development of Hepatocellular Carcinoma following Hepatitis C Virus Eradication Using Direct-Acting Antiviral Agents

Abstract

<b><i>Introduction:</i></b> Our previous studies showed that serum angiopoietin-2 (Ang-2) and C-X-C motif chemokine ligand 10 (CXCL10) levels predicted improvement in liver fibrosis following sustained virological response (SVR) of hepatitis C virus (HCV) obtained with administration of with direct-acting antiviral agents (DAAs). These levels were evaluated retrospectively as predictive indicators of hepatocellular carcinoma (HCC) development following SVR. <b><i>Methods:</i></b> We enrolled individuals from a historical cohort of 89 chronic HCV patients without history of HCC at baseline and with SVR following DAA therapy and had baseline serum levels of Mac-2 binding protein glycosylation isomer ≥2.0 cut-off index (C.O.I.). <b><i>Results:</i></b> Multivariate analyses revealed that only the Ang-2 level at 24 weeks following the end of treatment (EOT24W) was significantly related to HCC development (hazard ratio 2.27; <i>p</i> = 0.003). This result was reproduced in individuals without history of HCC and with advanced liver fibrosis (M2BPGi level ≥3.3 C.O.I. at baseline). Time-dependent receiver operating characteristic curve analyses for the future risk of developing HCC within 5 years of follow-up (5y-HCC) showed the best cut-off Ang-2 level at the EOT24W was 2,780 pg/mL, and significantly stratified the cumulative incidence of HCC (≥2,780 vs. &lt; 2,780 pg/mL, 5y-HCC: 45.5 vs. 8.2%, <i>p</i> &lt; 0.001). <b><i>Conclusions:</i></b> At the EOT24W, serum Ang-2 level predicts the likelihood of developing HCC following SVR to DAA therapy.