French Audrey L, Martin Jonathan W, Evans Charlesnika T, Peters Marion, Kessaye Seble G, Nowicki Marek, Kuniholm Mark, Golub Elizabeth, Augenbraun Michael, Desai Seema N
*CORE Center/Stroger (Cook County) Hospital, Chicago, IL;†Rush University Medical Center, Chicago, IL;‡Hines VA Medical Center, Chicago, IL;§Northwestern University Medical Center, Chicago, IL;‖University of California, San Francisco, CA;¶Georgetown University Medical Center, Washington, DC;#Mendez National Institute of Transplantation Foundation, Los Angeles, CA;**Department of Epidemiology & Population Health, University at Albany, State University of New York, Rensselaer, NY;††Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; and‡‡Department of Medicine, State University of New York Downstate, Brooklyn, NY.
J Acquir Immune Defic Syndr. 2017 Dec 1;76(4):438-444. doi: 10.1097/QAI.0000000000001524.
HIV/hepatitis C-coinfected persons experience more rapid liver disease progression than hepatitis C virus (HCV) monoinfected persons, even in the setting of potent antiretroviral therapy.
We sought to articulate the role of macrophage activation and inflammation in liver disease progression by measuring serial soluble markers in HIV/HCV-coinfected women. We compared markers measured during retrospectively defined periods of rapid liver disease progression to periods where little or no liver disease progression occurred. Liver disease progression was defined by liver biopsy, liver-related death or the serum markers AST-to-platelet ratio index and FIB-4. Soluble CD14, sCD163, lipopolysaccharide (LPS), tumor necrosis factor (TNF) receptor II, interleukin-6, and chemokine ligand 2 (CCL 2) were measured at 3 time points over 5 years.
One hundred six time intervals were included in the analysis: including 31 from liver disease progressors and 75 from nonprogressors. LPS, sCD14, interleukin-6, and CCL2 levels did not differ in slope or quantity over time between rapid liver disease progressors and nonprogressors. TNFRII and sCD163 were significantly higher in liver disease progressors at (P = 0.002 and <0.0001 respectively) and preceding (P = 0.01 and 0.003 respectively) the liver fibrosis outcome in unadjusted models, with similar values when adjusted for HIV RNA and CD4 count.
In women with HIV/HCV coinfection, higher sCD163 levels, a marker of macrophage activation, and TNFRII levels, implying activation of the TNF-α system, were associated with liver disease progression. Our results provide an addition to the growing body of evidence regarding the relationship between macrophage activation, inflammation, and liver disease progression in HIV/HCV coinfection.
即使在高效抗逆转录病毒治疗的情况下，合并感染人类免疫缺陷病毒（HIV）/丙型肝炎病毒（HCV）的患者比单纯感染HCV的患者肝病进展更快。
我们试图通过检测HIV/HCV合并感染女性的一系列可溶性标志物来阐明巨噬细胞活化和炎症在肝病进展中的作用。我们比较了在回顾性定义的肝病快速进展期与肝病进展很少或没有进展期所检测的标志物。肝病进展通过肝活检、肝病相关死亡或血清标志物AST与血小板比值指数及FIB-4来定义。在5年中的3个时间点检测可溶性CD-14、sCD163、脂多糖（LPS）、肿瘤坏死因子（TNF）受体II、白细胞介素-6和趋化因子配体2（CCL 2）。
分析纳入了106个时间间隔：包括来自肝病进展者的31个和来自非进展者的75个。在肝病快速进展者和非进展者之间，LPS、sCD14、白细胞介素-6和CCL2水平随时间的斜率或数量没有差异（P = 0.002和<0.0001），且在未调整模型中，在肝纤维化结果出现时（分别为P = 0.01和0.003）及之前，肝病进展者的TNFRII和sCD163显著更高，在根据HIV RNA和CD4计数进行调整后，结果相似（P = 0.01和0.003）。
在HIV/HCV合并感染的女性中，较高的sCD163水平（巨噬细胞活化的标志物）和TNFRII水平（意味着TNF-α系统的活化）与肝病进展相关。我们的结果为关于HIV/HCV合并感染中巨噬细胞活化、炎症和肝病进展之间关系的越来越多的证据增添了内容。
