Mascia Claudia, Lichtner Miriam, Zuccalà Paola, Vita Serena, Tieghi Tiziana, Marocco Raffaella, Savinelli Stefano, Rossi Raffaella, Iannetta Marco, Campagna Michela, Schiavone Francesco, Mengoni Fabio, Russo Gianluca, Mastroianni Claudio Maria, Vullo Vincenzo
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00155 Rome, Italy.
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00155 Rome, Italy; Infectious Diseases Unit, Sapienza University, S. M. Goretti Hospital, Corso della Repubblica 79, 04100 Latina, Italy.
Clin Res Hepatol Gastroenterol. 2017 Dec;41(6):644-655. doi: 10.1016/j.clinre.2017.04.007. Epub 2017 May 31.
Interferon-gamma (IFN-γ)-inducible protein-10 (IP-10), soluble (s) CD163 and sCD14 play an important role in the pathogenesis of HCV and HIV infection and are involved in inflammation and liver fibrosis. The aim of the present study was to evaluate at a single time point, plasma soluble biomarkers and inflammatory monocytes subsets in different groups of subjects: (i) HIV monoinfected patients on suppressive ART; (ii) HIV/HCV coinfected patients on ART, with undetectable HIV viremia (including either subjects who had active HCV replication or those who cleared HCV); (iii) HCV monoinfected individual with active viral replication.
Hundred and twenty-nine plasma samples were analyzed including HCV and HIV monoinfected patients, HIV/HCV coinfected patients, with active HCV infection (AHI) or with HCV viral clearance (VHC) and healthy donors (HD). Levels of IP-10, sCD163 and sCD14 were measured by ELISA. Absolute cell counts of monocyte subpopulations were enumerated in whole blood by using flow cytometric analyses.
IP-10 and sCD163 plasma levels were higher in HCV monoinfected and in AHI coinfected pts compared to HIV monoinfected and HD, whereas sCD14 levels were higher only in HIV monoinfected patients. Considering the degree of fibrosis, sCD163 and sCD14 levels positively correlated with kPa values (as assessed by fibroscan) and FIB-4 in HCV monoinfected group. On the other hand, IP-10 did not correlate with the fibrosis stage and it was found increased also in patients with low fibrosis. Moreover, we found an increase of the inflammatory NCM subset, in non-cirrhotic HCV subjects, while no alterations were observed in HIV, AHI and VHC.
Our study suggests a scenario in which active HCV infection is associated with a strong pro-inflammatory state, even in the initial stage of liver fibrosis, regardless the presence of HIV coinfection, thus underlying the need of an early anti-HCV treatment.
干扰素-γ（IFN-γ）诱导蛋白-10（IP-10）、可溶性（s）CD163和sCD14在丙型肝炎病毒（HCV）和人类免疫缺陷病毒（HIV）感染的发病机制中起重要作用，并参与炎症和肝纤维化过程。本研究的目的是在单个时间点评估不同组受试者的血浆可溶性生物标志物和炎性单核细胞亚群：（i）接受抑制性抗逆转录病毒治疗（ART）的HIV单感染患者；（ii）接受ART治疗且HIV病毒血症检测不到的HIV/HCV合并感染患者（包括HCV有活跃复制或已清除HCV的受试者）；（iii）有活跃病毒复制的HCV单感染个体。
分析了129份血浆样本，包括HCV和HIV单感染患者、HIV/HCV合并感染患者（有活跃HCV感染（AHI）或HCV病毒清除（VHC））以及健康供者（HD）。通过酶联免疫吸附测定（ELISA）法检测IP-10、sCD163和sCD14的水平。使用流式细胞术分析全血中单核细胞亚群的绝对细胞计数。
与HIV单感染患者和健康供者相比，HCV单感染患者和AHI合并感染患者的血浆IP-10和sCD163水平更高，而sCD14水平仅在HIV单感染患者中更高。考虑到纤维化程度，在HCV单感染组中，sCD163和sCD14水平与kPa值（通过FibroScan评估）和FIB-4呈正相关。另一方面，IP-10与纤维化阶段无关，且在低纤维化患者中也发现其升高。此外，我们发现非肝硬化HCV受试者中炎性非经典单核细胞（NCM）亚群增加，而在HIV、AHI和VHC患者中未观察到变化。
我们的研究表明，即使在肝纤维化的初始阶段，无论是否合并HIV感染，活跃的HCV感染都与强烈的促炎状态相关，因此强调了早期抗HCV治疗的必要性。
