Villani Rosanna, Facciorusso Antonio, Bellanti Francesco, Tamborra Rosanna, Piscazzi Annamaria, Landriscina Matteo, Vendemiale Gianluigi, Serviddio Gaetano
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.
Medical Oncology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
PLoS One. 2016 Dec 20;11(12):e0167934. doi: 10.1371/journal.pone.0167934. eCollection 2016.
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.
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.
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.
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.
新型直接抗病毒药物（DAAs）因其高效性和良好的安全性，彻底改变了丙型肝炎的治疗局面。不幸的是，有报道称在开始治疗数周内肝细胞癌早期复发率意外地高，但机制尚不清楚。
我们监测了103例接受DAA方案抗病毒治疗的慢性丙型肝炎患者血清血管内皮生长因子（VEGF）水平以及循环白细胞介素模式的变化。在基线、治疗期间和治疗后评估VEGF、表皮生长因子（EGF）和几种白细胞介素。还证实了DAA治疗患者血清对人脐静脉内皮细胞（HUVEC）增殖的生物学效应。
治疗4周后，VEGF水平相比基线升高约4倍，直至治疗结束一直保持升高，治疗结束后恢复到治疗前水平。相比之下，白细胞介素-10和肿瘤坏死因子-α在治疗期间显著下降，这与HCV清除相一致。治疗后两者水平均保持较低。添加治疗期间收集的患者血清可诱导HUVEC增殖；然而，治疗结束后这种情况消失。
给予DAA会导致血清VEGF早期升高以及炎症模式改变，这与HCV清除同时发生。这可能会改变炎症和抗炎过程之间的平衡，并改变宿主的抗肿瘤监测。幸运的是，治疗结束后这些改变会恢复正常。
