背景:乙型肝炎病毒(HBV)和人类免疫缺陷病毒(HIV)共同感染是重要的公共卫生问题,尽管近三十年来有效的HBV疫苗的可用性以及在预防和治疗HIV方面取得的巨大进展。HBV和HIV都调节微核糖核酸(microRNA)表达以支持病毒复制。这项研究的目的是描述在合并感染慢性HBV和HIV与不同疾病严重程度的患者microRNA表达的模式,如乙型肝炎e抗原(HBeAg)状态所示,HBV病毒载量,丙氨酸转氨酶(ALT)水平,和HIV病毒载量。
方法:血浆微小RNA,特定于HBV,通过定量实时聚合酶链反应(qRT-PCR)在HBV和HIV阴性健康对照(n=23)和合并感染慢性HBV-HIV的患者(n=50)中进行测量。MicroRNA表达水平比较高与低HBV病毒载量患者之间,HBeAg阳性与HBeAg阴性,高与低ALT水平,和高与低HIV病毒载量。此外,HBV病毒载量,ALT水平,HIV病毒载量与microRNA表达水平相关。
结果:与健康对照相比,在慢性HBV-HIV共感染患者中观察到所选microRNAs的表达水平明显更高。hsa-miR-122-5p的表达水平显著升高,hsa-miR-192-5p,和hsa-miR-193b-3p观察到高HBV病毒载量患者与低HBV病毒载量患者相比,这些微小RNA的水平与HBV病毒载量水平相关。在HBeAg阴性患者中观察到显著更高水平的hsa-miR-15b-5p和hsa-miR-181b-5p。
结论:这项研究证明了hsa-miR-15b-5p的潜在用途,hsa-miR-122-5p,hsa-miR-181b-5p,hsa-miR-192-5p和hsa-miR-193b-3p作为慢性HBV疾病进展的额外诊断生物标志物。
BACKGROUND: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection are significant public health issues, despite the availability of an effective HBV vaccine for nearly three decades and the great progress that has been made in preventing and treating HIV. HBV and HIV both modulate micro-ribonucleic acids (
microRNA) expression to support viral replication. The aim of this study was to describe the pattern of
microRNA expression in patients coinfected with chronic HBV and HIV with varying disease severity, as indicated by Hepatitis B e antigen (HBeAg) status, HBV viral load, alanine transaminase (ALT) levels, and HIV viral load.
METHODS: Plasma microRNAs, specific to HBV, were measured by quantitative real-time polymerase chain reaction (qRT-PCR) in HBV and HIV-negative healthy controls (n = 23) and patients coinfected with chronic HBV-HIV (n = 50).
MicroRNA expression levels were compared between patients with high vs low HBV viral load, HBeAg positive vs HBeAg negative, high vs low ALT levels, and high vs low HIV viral load. Additionally, HBV viral load, ALT levels, and HIV viral load were correlated with
microRNA expression levels.
RESULTS: Significantly higher expression levels of selected microRNAs were observed in chronic HBV-HIV coinfected patients compared to healthy controls. Significantly higher expression levels of hsa-miR-122-5p, hsa-miR-192-5p, and hsa-miR-193b-3p were observed in patients with high HBV viral load compared with low HBV viral load patients, and the levels of these microRNAs were correlated with HBV viral load levels. Significantly higher levels of hsa-miR-15b-5p and hsa-miR-181b-5p were observed in HBeAg-negative patients.
CONCLUSIONS: This study demonstrates the potential use of hsa-miR-15b-5p, hsa-miR-122-5p, hsa-miR-181b-5p, hsa-miR-192-5p and hsa-miR-193b-3p as additional diagnostic biomarkers in chronic HBV disease progression.