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Effect of interferon-based and -free therapy on early occurrence and recurrence of hepatocellular carcinoma in chronic hepatitis C

      Highlights

      • The risks of early HCC after viral eradication were similar between IFN-based and-free therapies.
      • Post-treatment levels of WFA+M2BP may be helpful for screening biomarkers to assess the risks of HCC.
      • Post-treatment WFA+M2BP was identified independently from liver fibrosis as a factor associated with HCC.

      Background and Aims

      Although treatment for hepatitis C virus has been dramatically improved by the development of direct-acting antiviral agents (DAAs), whether interferon (IFN)-free therapy reduces hepatocarcinogenesis in an equivalent manner to IFN-based therapy remains controversial. The aims of this study were to evaluate the occurrence and recurrence of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients treated with DAAs and to identify biomarkers of HCC development after antiviral treatment.

      Methods

      A restrospective review of a prospective database of 1,897 CHC patients who were treated with IFN-based (1,145) or IFN-free therapies (752) was carried out. Cumulative HCC occurrence and recurrence rates were compared using propensity score-matched analysis. Predictors of HCC development after viral eradication were identified by multivariate analysis.

      Results

      Propensity score-matched analysis showed no significant difference in HCC occurrence (p = 0.49) and recurrence rates (p = 0.54) between groups treated with IFN-based or IFN-free therapies. In multivariate analysis, higher levels of post-treatment α-fetoprotein (AFP) or Wisteria floribunda agglutinin positive Mac-2 binding protein (WFA+M2BP) were independently associated with HCC occurrence and recurrence after viral eradication. Only post-treatment WFA+M2BP level was significantly associated with HCC occurrence and recurrence among patients without severe fibrosis. The area under the receiver operating characteristic (ROC) curve for WFA+M2BP levels was greater than that for AFP levels in ROC analysis.

      Conclusion

      The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFN-free therapies. Post-treatment levels of WFA+M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy. Patients with high WFA+M2BP levels after antiviral treatment, even without severe fibrosis, must be followed up carefully for HCC development.
      Lay summary: The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFN-free therapies. Post-treatment levels of WFA+M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy.

      Graphical abstract

      Keywords

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      Linked Article

      • Imaging basis of AFP and WFA+M2BP as indicators of the risk of HCC after SVR
        Journal of HepatologyVol. 68Issue 3
        • Preview
          We read with great interest the article by Nagata et al.1 on the risk of developing hepatocellular carcinoma (HCC) after the eradication of hepatitis C virus (HCV) in patients with chronic hepatitis C who achieved a sustained virologic response (SVR). The authors reported that post-treatment serum alpha-fetoprotein (AFP) and Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+M2BP) are indicators of the risk of HCC development after SVR. To elucidate the link between the serum levels of these markers and the incidence of HCC development after SVR, we investigated the association between the post-treatment levels of these serum markers and liver imaging findings before anti-HCV therapy.
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      • Reply to: “Imaging Basis of AFP and WFA+M2BP as Indicators of the risk of HCC after SVR”
        Journal of HepatologyVol. 68Issue 3
        • Preview
          We appreciate the valuable comments that Toyoda et al. suggest in relation to our manuscript. We approve of the data that the presence of non-hypervascular hypointense nodules before anti-HCV therapy was associated with high post-treatment levels of AFP or Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+M2BP). We also analyzed 116 patients without a history of HCC who underwent Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) prior to the start of anti-HCV direct-acting antiviral (DAA) therapy and achieved a sustained virologic response (SVR) between October 2014 and January 2017.
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