Supplementary Material for: Serum angiopoietin-2 levels predict the development of hepatocellular carcinoma following hepatitis C virus eradication using direct-acting antiviral agents

Introduction: 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.
Methods: 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 C.O.I.
Results: 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; P = 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. < 2,780 pg/mL, 5y-HCC: 45.5 vs. 8.2%, P < 0.001).
Conclusions: At the EOT24W, serum Ang-2 level predicts the likelihood of developing HCC following SVR to DAA therapy.