Department of Medicine, Imperial College London, London, United Kingdom.
PLoS One. 2012;7(7):e38980. doi: 10.1371/journal.pone.0038980. Epub 2012 Jul 12.
Microglial cell activation and cerebral function impairment are described in both chronic hepatitis C viral (HCV) and Human-Immune-Deficiency viral (HIV) infections. The aim of this study was to investigate the effect of acute HCV infection upon cerebral function and microglial cell activation in HIV-infected individuals.
A case-control study was conducted. Subjects with acute HCV and chronic HIV coinfection (aHCV) were compared to matched controls with chronic HIV monoinfection (HIVmono). aHCV was defined as a new positive plasma HCV RNA within 12 months of a negative RNA test. Subjects underwent neuro-cognitive testing (NCT), cerebral proton magnetic resonance spectroscopy ((1)H-MRS) and positron emission tomography (PET) using a (11)C-radiolabeled ligand (PK11195), which is highly specific for translocator protein 18 kDA receptors on activated microglial cells. Differences between cases and controls were assessed using linear regression modelling.
Twenty-four aHCV cases completed NCT and (1)H-MRS, 8 underwent PET. Of 57 HIVmono controls completing NCT, 12 underwent (1)H-MRS and 8 PET. Subjects with aHCV demonstrated on NCT, significantly poorer executive function (mean (SD) error rate 26.50(17.87) versus 19.09(8.12), p = 0.001) and on (1)H-MRS increased myo-inositol/creatine ratios (mI/Cr, a marker of cerebral inflammation) in the basal ganglia (ratio of 0.71(0.22) versus 0.55(0.23), p = 0.03), compared to subjects with HIVmono. On PET imaging, no difference in (11)C-PK11195 binding potential (BP) was observed between study groups (p>0.10 all cerebral locations), however lower BPs were associated with combination antiretroviral therapy (cART) use in the parietal (p = 0.01) and frontal (p = 0.03) cerebral locations.
Poorer cognitive performance and disturbance of cerebral metabolites are observed in subjects with aHC,V compared to subjects with HIVmono. Higher (11)C-PK11195 BP was not observed in subjects with aHCV, but was observed in subjects not on cART.
慢性丙型肝炎病毒（HCV）和人类免疫缺陷病毒（HIV）感染均可导致小胶质细胞激活和脑功能损害。本研究旨在探讨急性 HCV 感染对 HIV 感染者脑功能和小胶质细胞激活的影响。
采用病例对照研究。将急性 HCV 和慢性 HIV 合并感染（aHCV）患者与慢性 HIV 单一感染（HIVmono）的匹配对照进行比较。aHCV 定义为在阴性 RNA 检测后 12 个月内新出现的阳性血浆 HCV RNA。受试者接受神经认知测试（NCT）、质子磁共振波谱（1H-MRS）和正电子发射断层扫描（PET），使用（11）C 放射性标记配体（PK11195），该配体高度特异性地与激活的小胶质细胞上的转位蛋白 18 kDa 受体结合。采用线性回归模型评估病例组与对照组之间的差异。
24 例 aHCV 患者完成了 NCT 和 1H-MRS，8 例进行了 PET。57 例 HIVmono 对照组中，12 例完成了 NCT，8 例进行了 PET。aHCV 患者的 NCT 表现为执行功能明显较差（平均（SD）错误率 26.50（17.87）比 19.09（8.12），p = 0.001），1H-MRS 显示基底节区肌醇/肌酸比（mI/Cr，脑炎症标志物）升高（比值为 0.71（0.22）比 0.55（0.23），p = 0.03），与 HIVmono 患者相比。在 PET 成像中，研究组之间（11）C-PK11195 结合潜能（BP）无差异（所有脑区均>0.10），但在顶叶（p = 0.01）和额叶（p = 0.03）脑区，BP 与联合抗逆转录病毒治疗（cART）的使用呈负相关。
与 HIVmono 患者相比，aHCV 患者的认知功能表现较差，脑代谢物紊乱。在 aHCV 患者中未观察到较高的（11）C-PK11195 BP，但在未接受 cART 的患者中观察到。
