Levels of Cytokines in Serum Associate With Development of Hepatocellular Carcinoma in Patients With HCV Infection Treated With Direct-Acting Antivirals

Jose D. Debes, Marjolein van Tilborg, Zwier M.A. Groothuismink, Bettina E. Hansen, Julian Schulze zur Wiesch, Johann von Felden, Robert J. de Knegt, Andre Boonstra

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Concern has arisen about the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs). To identify patients at risk for HCC, we evaluated serum levels of immune mediators before, during, and after DAA treatment of HCV infection. Our study included 13 patients who developed HCC within 18 months after treatment (3 with HCC recurrence and 10 with new HCC) and 10 patients who did not develop HCC (controls), within at least 24 months of treatment (median, 26 months). We identified a set of 12 immune mediators (cytokines, growth factors, and apoptosis markers) whose levels were significantly higher in serum before DAA treatment of patients who eventually developed de novo HCC compared with controls. A panel of 9 cytokines, measured in serum before treatment (MIG, IL22, TRAIL, APRIL, VEGF, IL3, TWEAK, SCF, IL21), identified patients who developed de novo HCC with an area under the receiver operating characteristic curve value higher than 0.8. Further analyses of changes in levels of inflammatory cytokines during DAA treatment also provides important information about HCV-induced carcinogenesis and the effects of DAAs.

Original languageEnglish (US)
Pages (from-to)515-517.e3
JournalGastroenterology
Volume154
Issue number3
DOIs
StatePublished - Feb 2018

Bibliographical note

Funding Information:
vF and SzW are supported by the German Research Agency (DFG). SzW is supported by the German Center for Infection (DZIF).

Funding Information:
Funding The authors are supported by the Virgo consortium, funded by the Dutch government ( FES0908 ), and the Harold Amos Medical Faculty Development Program (74249) (to J.D.D.).

Publisher Copyright:
© 2018 AGA Institute

Keywords

  • AUROC
  • Biomarker
  • Interleukin
  • Liver Cancer
  • Prognostic Factor

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