Circulating MicroRNAs as a Marker for Liver Injury in Human Immunodeficiency Virus Patients
Circulating MicroRNAs as a Marker for Liver Injury in Human Immunodeficiency Virus Patients
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DOI：
10.1002/hep.27369
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发表时间：
2015-01-01
期刊：
影响因子：
13.5
通讯作者：
Trebicka, Jonel
中科院分区：
文献类型：
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作者：
Anadol, Evrim;Schierwagen, Robert;Trebicka, Jonel
人类免疫缺陷病毒（HIV）和肝炎病毒合并感染可放大和加速肝损伤。microRNA（miRNAs）是一种小的调控RNA，被认为是肝损伤的生物标志物。我们分析了HIV患者中miRNA的循环水平与肝损伤的程度和病因。使用Qiazol从335名HIV患者和22名健康对照者的血清样品中提取总RNA。对8例HIV、8例HIV/HCV（丙型肝炎病毒）、6例HCV患者和3例健康对照的血清样本进行了全面的聚合酶链反应（PCR）阵列分析（768 miRNA）。逆转录（RT）-PCR测量了335名患者和19名健康对照参与者血清样本中miRNA-122，miRNA-22和miRNA-34 a的水平。这些患者的肝损伤和肝纤维化通过天冬氨酸转氨酶（AST）水平、纤维化-4（FIB-4）指数和AST与血小板比率指数（APRI）评分来定义。与HCV和HIV感染相比，HIV/HCV样本的miRNA模式分别显示57和33个miRNA的表达改变。miRNA-122、miRNA-22和miRNA-34 a在HIV/HCV患者中高度上调。分析整个队列，这些miRNAs与肝功能检查相关，并且是肝损伤的独立预测因子（AST >2 x ULN）。miRNA-122和miRNA-22与相关纤维化相关（FIB-4 >1.45; APRI >1）。miRNA-122的循环水平是HIV患者相关纤维化的独立预测因子。有趣的是，miRNA-122和miRNA-34 a水平在HIV/HCV患者中较高，miRNA-22水平在HIV/HBV患者中最高，并且miRNA-34 a的循环水平与非法药物使用和乙醇消耗呈正相关。结论：循环miRNA-122、miRNA-22和miRNA-34 a与HIV患者肝损伤的病因相关。这些生物标志物不仅反映了肝损伤的不同机制，而且是HIV患者肝损伤的独立预测因子。（肝病学2015;61：46-55）
Human immunodeficiency virus (HIV) and hepatitis virus coinfection amplify and accelerate hepatic injury. MicroRNAs (miRNAs) are small regulatory RNAs suggested as biomarkers for liver injury. We analyzed the circulating levels of miRNAs in HIV patients with regard to the extent and etiology of liver injury. Total RNA was extracted from 335 serum samples of HIV patients and 22 healthy control participants using Qiazol. Comprehensive polymerase chain reaction (PCR) array analyses (768 miRNA) were performed in serum samples of eight HIV, eight HIV/HCV (hepatitis C virus), six HCV patients, and three healthy controls. Reverse transcription (RT)-PCR measured levels of miRNA-122, miRNA-22, and miRNA-34a in serum samples of 335 patients and 19 healthy control participants. Liver injury and fibrosis in these patients were defined using aspartate aminotransferase (AST) levels, fibrosis-4 (FIB-4) index and AST-to-platelet ratio index (APRI) score. The miRNA pattern of HIV/HCV samples showed altered expression of 57 and 33 miRNA compared to HCV and HIV infection, respectively. miRNA-122, miRNA-22, and miRNA-34a were highly up-regulated in HIV/HCV patients. Analyzing the entire cohort, these miRNAs were correlated with liver function tests and were independent predictors of liver injury (AST >2 x ULN). miRNA-122 and miRNA-22 were associated with relevant fibrosis (FIB-4 >1.45; APRI >1). Circulating levels of miRNA-122 were independent predictors for relevant fibrosis in HIV patients. Interestingly, miRNA-122 and miRNA-34a levels were higher in HIV/HCV patients, miRNA-22 levels were highest in HIV/HBV patients, and circulating levels of miRNA-34a correlated positively with illicit drug use and ethanol consumption. Conclusion: Circulating miRNA-122, miRNA-22, and miRNA-34a correlates with the etiology of liver injury in HIV patients. These biomarkers not only mirror different mechanisms of hepatic injury, but also are independent predictors of liver injury in HIV patients. (Hepatology 2015;61:46-55)