Armah Kaku A, Quinn Emily K, Cheng Debbie M, Tracy Russell P, Baker Jason V, Samet Jeffrey H, Freiberg Matthew S
Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.
BMC Infect Dis. 2013 Aug 29;13:399. doi: 10.1186/1471-2334-13-399.
Assessing whether hepatitis C (HCV) co-infection with human immunodeficiency virus (HIV) is associated with increased inflammation is complex. The liver, integral to inflammatory biomarker synthesis, is compromised by HCV and alcohol abuse. Using single liver-synthesized biomarkers (e.g. C-reactive protein) to represent inflammation may not be appropriate in HIV/HCV co-infection. We hypothesized that 1) detectable HIV/HCV RNA was independently associated with increased inflammation; 2) a composite inflammation measure describes inflammation differently from single inflammatory biomarkers.
We compared inflammation by HIV/HCV group in a cohort of 361 HIV infected participants from the HIV-Longitudinal Interrelationships of Viruses and Ethanol study. Inflammatory biomarkers >75th percentile were considered elevated. Associations between HIV/HCV group and elevated biomarkers were analyzed as a composite measure (inflammatory burden) or individually. We defined inflammatory burden as number of concurrently elevated biomarkers. Biomarkers included interleukin-6 (IL-6), C-reactive protein (CRP), cystatin C, serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10). Covariates: alcohol, liver fibrosis, comorbidities, CD4 count, antiretroviral therapy, substance use.
Detectable HIV and HCV RNA (OR = 2.49; 95% CI = 1.05-5.89) and detectable HCV RNA alone (2.95; 1.08-8.01) were independently associated with increased odds of having a greater inflammatory burden compared to undetectable viremia. Elevated IL-10 (7.79; 1.90-31.97) and TNF-α (7.70; 1.42-41.83) were independently associated with detectable HIV and HCV RNA. Elevated IL-10 was also associated with detectable HCV RNA alone (5.51; 1.17, 25.84).
Detectable HIV and HCV replication versus undetectable replication was associated with inflammatory burden and certain inflammatory biomarkers independently of alcohol consumption, liver fibrosis and other comorbidities.
评估丙型肝炎病毒(HCV)与人类免疫缺陷病毒(HIV)合并感染是否与炎症增加相关是复杂的。肝脏是炎症生物标志物合成的重要场所,却因HCV和酒精滥用而受损。在HIV/HCV合并感染中,使用单一肝脏合成的生物标志物(如C反应蛋白)来代表炎症可能并不合适。我们假设:1)可检测到的HIV/HCV RNA与炎症增加独立相关;2)综合炎症指标对炎症的描述与单一炎症生物标志物不同。
我们在一项来自“病毒与乙醇的HIV纵向相互关系”研究的361名HIV感染参与者队列中,比较了HIV/HCV组之间的炎症情况。炎症生物标志物高于第75百分位数被视为升高。将HIV/HCV组与升高的生物标志物之间的关联作为综合指标(炎症负担)或单独进行分析。我们将炎症负担定义为同时升高的生物标志物数量。生物标志物包括白细胞介素-6(IL-6)、C反应蛋白(CRP)、胱抑素C、血清淀粉样蛋白A(SAA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)。协变量包括:酒精、肝纤维化、合并症、CD4细胞计数、抗逆转录病毒治疗、物质使用情况。
与无法检测到病毒血症相比,可检测到的HIV和HCV RNA(比值比[OR]=2.49;95%置信区间[CI]=1.05-5.89)以及仅可检测到的HCV RNA(2.95;1.08-8.01)与炎症负担增加的几率独立相关。IL-10升高(7.79;1.90-31.97)和TNF-α升高(7.70;1.42-41.83)与可检测到的HIV和HCV RNA独立相关。IL-10升高也与仅可检测到的HCV RNA相关(5.51;1.17,25.84)。
与无法检测到复制相比,可检测到的HIV和HCV复制与炎症负担及某些炎症生物标志物相关,且独立于酒精摄入、肝纤维化和其他合并症。