Kamar Nassim, Rostaing Lionel, Sandres-Saune Karine, Selves Janick, Barthe Carole, Dubois Martine, Alric Laurent, Durand Dominique, Izopet Jacques
Department of Nephrology, Dialysis and Multiorgan Transplantation, CHU Rangueil, Toulouse, France.
J Med Virol. 2005 Aug;76(4):482-8. doi: 10.1002/jmv.20387.
In order to examine the immunopathogenesis of hepatitis C virus (HCV)-related liver injury in renal-transplant patients, intra-hepatic cytokine profiles were examined in 38 liver biopsies from 38 patients by measuring messenger RNA (mRNA) concentrations by a real-time PCR method of a Th1 cytokine (i.e., interferon (IFN)-gamma), a Th2 cytokines (i.e., interleukine (IL)-10), a proinflammatory cytokine (i.e., IL-8), and a potent fibrogenic factor (transforming growth factor [TGF]-beta). There was no significant difference in TGF-beta, IFN-gamma, IL-10, or IL-8 levels of expression according to liver-activity grade, liver-fibrosis stage, the concentration of HCV RNA at liver biopsies, or the HCV genotype. However, IFN-gamma/beta-actin mRNA concentration was higher than the IL-10/beta-actin mRNA concentration in patients with F3 Metavir score. Median IFN-gamma/beta-actin mRNA concentration tended to be higher in patients with A3 and A4 Metavir activity grades compared with those with A0 and A1 activity grades. There was a significant correlation between the duration of HCV infection and both TGF-beta/beta-actin (r(2)=0.19, P=0.04) and IL-8/beta-actin mRNA concentrations (r(2)=0.19, P=0.03). IFN-gamma/beta-actin mRNA concentration also increased according to the duration of HCV (r(2)=0.19, P=0.07). Finally, there was a significant correlation between the duration of HCV infection and liver fibrosis stage (r(2)=0.17, P=0.045). Intrahepatic Th1 cytokine profile seems to be predominant in patients with extensive fibrosis and activity scores, suggesting that it might be responsible for liver injury in renal transplant patients.
为了研究肾移植患者丙型肝炎病毒（HCV）相关肝损伤的免疫发病机制，通过实时聚合酶链反应（PCR）法测量38例患者38份肝活检组织中Th1细胞因子（即干扰素（IFN）-γ）、Th2细胞因子（即白细胞介素（IL）-10）、促炎细胞因子（即IL-8）和强效纤维化因子（转化生长因子（TGF）-β）的信使核糖核酸（mRNA）浓度，检测肝内细胞因子谱。根据肝活动度分级、肝纤维化分期、肝活检时HCV RNA浓度或HCV基因型，TGF-β、IFN-γ、IL-10或IL-8的表达水平无显著差异。然而，F3 Metavir评分患者的IFN-γ/β-肌动蛋白mRNA浓度高于IL-10/β-肌动蛋白mRNA浓度。与A0和A1活动度分级的患者相比，A3和A4 Metavir活动度分级的患者中IFN-γ/β-肌动蛋白mRNA浓度中位数往往更高。HCV感染持续时间与TGF-β/β-肌动蛋白（r²=0.19，P=0.04）和IL-8/β-肌动蛋白mRNA浓度（r²=0.19，P=0.03）均存在显著相关性。IFN-γ/β-肌动蛋白mRNA浓度也随HCV感染持续时间增加（r²=0.19，P=0.07）。最后，HCV感染持续时间与肝纤维化分期存在显著相关性（r²=0.17，P=0.045）。肝内Th1细胞因子谱在广泛纤维化和活动度评分的患者中似乎占主导地位，提示其可能是肾移植患者肝损伤的原因。
