Radmanic Matotek Leona, Zidovec-Lepej Snjezana, Salek Nikolina, Vince Adriana, Papic Neven
Department of Immunological and Molecular Diagnostics, University Hospital for Infectious Diseases "Dr. Fran Mihaljević", 10000 Zagreb, Croatia.
Department for Viral Hepatitis, University Hospital for Infectious Diseases "Dr. Fran Mihaljević", 10000 Zagreb, Croatia.
J Clin Med. 2024 Aug 16;13(16):4849. doi: 10.3390/jcm13164849.
Various biological response modifiers play important roles in the immunopathogenesis of chronic hepatitis C (CHC). While serum levels of cytokines and growth factors change with the disease severity and treatment responses, the impact of concomitant liver steatosis on systemic inflammatory response is largely unknown. The aim of this study was to analyze the characteristics and kinetics of serum profiles of interleukins and growth factors in CHC patients with steatotic liver disease (SLD). Serum concentrations of 12 cytokines (IL-5, IL-13, IL-2, IL-6, IL-9, IL-10, IFN-γ, TNF-α, IL-17A, IL-17F, IL-4 and IL-22) and 6 growth factors (Angiopoietin-2, EGF, EPO, HGF, SCF, VEGF) were analyzed in 56 CHC patients at four time points (baseline, week 4, week 8 and SVR12) with bead-based flow cytometry assay. At baseline, patients with SLD had significantly lower IL-9, IL-10, IL-13 and IL-22 and higher serum concentrations of EGF, VEGF and ANG. In a subgroup of patients with advanced liver fibrosis, SLD was linked with lower serum concentrations of IL-4, IL-5, IL-9, IL-10, IL-13 and IL-22 and higher concentrations of HGH and VEGF. Distinct cytokine kinetics during DAA treatment was observed, and SLD was identified as the main source of variation for IL-5, IL-9, IL-10, IL-13, IL-17A, IL-22, EGF, VEGF and ANG. Patients with SLD at SVR12 had significantly higher VEGF and HGF serum concentrations. SLD is associated with distinct cytokine and growth factor profiles and kinetics during CHC treatment, which might be associated with disease severity and the capacity for liver regeneration and contribute to fibrosis persistence.
多种生物反应调节剂在慢性丙型肝炎（CHC）的免疫发病机制中发挥重要作用。虽然细胞因子和生长因子的血清水平随疾病严重程度和治疗反应而变化，但合并肝脂肪变性对全身炎症反应的影响在很大程度上尚不清楚。本研究的目的是分析合并脂肪性肝病（SLD）的CHC患者血清白细胞介素和生长因子谱的特征及动力学变化。采用基于微珠的流式细胞术分析了56例CHC患者在四个时间点（基线、第4周、第8周和SVR12）的12种细胞因子（IL-5、IL-13、IL-2、IL-6、IL-9、IL-10、IFN-γ、TNF-α、IL-17A、IL-17F、IL-4和IL-22）和6种生长因子（血管生成素-2、表皮生长因子、促红细胞生成素、肝细胞生长因子、干细胞因子、血管内皮生长因子）的血清浓度。在基线时，SLD患者的IL-9、IL-10、IL-13和IL-22水平显著较低，而表皮生长因子、血管内皮生长因子和血管生成素的血清浓度较高。在晚期肝纤维化患者亚组中，SLD与IL-4、IL-5、IL-9、IL-10、IL-13和IL-22的血清浓度较低以及生长激素和血管内皮生长因子浓度较高有关。在直接抗病毒药物治疗期间观察到不同的细胞因子动力学变化，且SLD被确定为IL-5、IL-9、IL-10、IL-13、IL-17A、IL-22、表皮生长因子、血管内皮生长因子和血管生成素变化的主要来源。SVR12时合并SLD的患者血清血管内皮生长因子和肝细胞生长因子浓度显著较高。SLD与CHC治疗期间不同的细胞因子和生长因子谱及动力学变化有关，这可能与疾病严重程度以及肝脏再生能力有关，并导致纤维化持续存在。
