Department of Immunological and Molecular Diagnostics, University Hospital for Infectious Diseases "Dr. Fran Mihaljević", 10000 Zagreb, Croatia.
Research Department, University Hospital for Infectious Diseases "Dr. Fran Mihaljević", 10000 Zagreb, Croatia.
Viruses. 2022 Jul 24;14(8):1613. doi: 10.3390/v14081613.
In this study, we evaluated the effect of hepatitis C virus eradication using direct-acting antivirals (DAA) on the serum cytokine and growth factor profiles of chronic hepatitis C patients (CHC). Serum concentrations of 12 cytokines and 13 growth factors were measured in 56 patients with CHC before, during the DAA treatment and after sustained virological response using bead-based flow cytometry. Cytokine and growth factor levels were also measured in 15 healthy individuals. The majority of the selected cytokines and growth factors exhibited similar concentrations before, during and after successful DAA treatment, the exceptions being IL-10, EGF, HGF and VEGF. Significantly lower concentrations of IL-10, IL-13, IL-4, IL-4, IL-9, TNF- α and higher levels of Ang-2, HGF and SCF were observed in patients with CHC before and after DAA treatment compared with healthy individuals. Patients with severe fibrosis stages exhibited higher levels of Ang-2 and lower levels of EGF, PDGF-AA and VEGF. Furthermore, IL-4, IL-5 and SCF were characterized as potential biomarkers of DAA treatment using random forest. Additionally, logistic regression characterized EGF as a potential biomarker of severe CHC. Our results suggest inhibition of pro-inflammatory processes and promotion of liver regeneration in CHC patients during DAA treatment.
在这项研究中，我们评估了使用直接作用抗病毒药物（DAA）清除丙型肝炎病毒对慢性丙型肝炎患者（CHC）血清细胞因子和生长因子谱的影响。使用基于珠的流式细胞术，在 56 例 CHC 患者接受 DAA 治疗前、治疗期间和持续病毒学应答后，测量了 12 种细胞因子和 13 种生长因子的血清浓度。还在 15 名健康个体中测量了细胞因子和生长因子的水平。大多数选定的细胞因子和生长因子在成功的 DAA 治疗前、治疗中和治疗后表现出相似的浓度，例外的是 IL-10、EGF、HGF 和 VEGF。与健康个体相比，CHC 患者在 DAA 治疗前和治疗后观察到 IL-10、IL-13、IL-4、IL-6、IL-9、TNF-α的浓度显著降低，而 Ang-2、HGF 和 SCF 的水平升高。纤维化严重程度较高的患者表现出更高水平的 Ang-2 和更低水平的 EGF、PDGF-AA 和 VEGF。此外，使用随机森林，IL-4、IL-5 和 SCF 被确定为 DAA 治疗的潜在生物标志物。此外，逻辑回归将 EGF 确定为严重 CHC 的潜在生物标志物。我们的研究结果表明，在 DAA 治疗期间，CHC 患者的促炎过程受到抑制，肝脏再生得到促进。
