title: DAAs Rapidly Reduce Inflammation but Increase Serum VEGF Level: A Rationale for Tumor Risk during Anti-HCV Treatment.
abstract: BACKGROUND
  Novel direct-acting antivirals (DAAs) have completely changed the panorama of hepatitis C due to their high efficacy and optimal safety profile. Unfortunately, an unexpectedly high rate of early recurrence of hepatocellular carcinoma has been reported within weeks of starting treatment, but the mechanism is not known.
  
  
  METHODS
  We monitored the serum level of vascular endothelial growth factor (VEGF) and changes in the pattern of circulating interleukins in 103 chronic hepatitis C patients during antiviral treatment with DAA-regimens. VEGF, epidermal growth factor (EGF), and several interleukins were assessed at baseline, during treatment, and after treatment. The biological effect of DAA-treated patient serum on human umbilical vein endothelial cell (HUVEC) proliferation was also confirmed.
  
  
  RESULTS
  After 4 weeks of therapy, VEGF increased approximately 4-fold compared to baseline, remained elevated up to the end of treatment, and returned to the pre-treatment level after the end of therapy. In contrast, interleukin-10 and tumor necrosis factor-alpha significantly decreased during therapy, which was coincident with HCV clearance. The levels of both remained low after treatment. The addition of serum from patients collected during therapy induced HUVEC proliferation; however, this disappeared after the end of therapy.
  
  
  CONCLUSIONS
  DAA administration induces an early increase in serum VEGF and a change in the inflammatory pattern, coinciding with HCV clearance. This may alter the balance between inflammatory and anti-inflammatory processes and modify the antitumor surveillance of the host. Fortunately, such modifications return reverse to normal after the end of treatment.
authors.affiliation: C.U.R.E. (Centro per la Ricerca e la Cura delle Epatopatie), Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Villani
authors.affiliation: C.U.R.E. (Centro per la Ricerca e la Cura delle Epatopatie), Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Facciorusso
authors.affiliation: C.U.R.E. (Centro per la Ricerca e la Cura delle Epatopatie), Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bellanti
authors.affiliation: C.U.R.E. (Centro per la Ricerca e la Cura delle Epatopatie), Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Tamborra
authors.affiliation: Medical Oncology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Piscazzi
authors.affiliation: Medical Oncology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.|Laboratory of Pre-Clinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Landriscina
authors.affiliation: C.U.R.E. (Centro per la Ricerca e la Cura delle Epatopatie), Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Vendemiale
authors.affiliation: C.U.R.E. (Centro per la Ricerca e la Cura delle Epatopatie), Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Serviddio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D049109:Cell Proliferation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000097:blood; D005260:Female; D016174:Hepacivirus / Q000378:metabolism*; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009369:Neoplasms; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D000998:Antiviral Agents; C508609:IL10 protein, human; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; D004815:Epidermal Growth Factor