Circulating miRNA-122 levels are associated with hepatic necroinflammation and portal hypertension in HIV/HCV coinfection.

Circulating miRNA-122 levels are associated with hepatic necroinflammation and portal hypertension in HIV/HCV coinfection.
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DOI:
10.1371/journal.pone.0116768
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Trebicka J
Trebicka J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Jansen C;Reiberger T;Huang J;Eischeid H;Schierwagen R;Mandorfer M;Anadol E;Schwabl P;Schwarze-Zander C;Warnecke-Eberz U;Strassburg CP;Rockstroh JK;Peck-Radosavljevic M;Odenthal M;Trebicka J

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联合抗逆转录病毒治疗(cART)的引入改善了HIV感染者的生存率,而肝脏相关死亡率的相对贡献增加了。特别是在HIV/HCV合并感染的患者中,肝纤维化和门静脉高压是肝脏相关疾病发病率和死亡率的主要原因。循环中的miRNA-122水平在HIV患者中升高,并已被证明与肝损伤的严重程度相关。然而,miRNA-122水平与肝纤维化和门脉高压症的关系在HIV/HCV合并感染中仍有待研究。共纳入74例(31%为女性)HIV/HCV合并感染患者。通过定量聚合酶链反应(PCR)分析miRNA-122的血清水平,并将其标准化为SV-40加标RNA。52例(70%)患者测量了肝静脉压力梯度(HVPG),63例(85%)患者使用瞬时弹性成像确定了纤维化分期。在HIV/HCV合并感染患者中,循环miRNA-122水平升高,并与丙氨酸氨基转移酶(ALT)(rs = 0.438; p<0.001)和天冬氨酸氨基转移酶AST值(rs = 0.336; p = 0.003)显著相关,但与纤维化分期无关(p = n.s.)。有趣的是,miRNA-122水平与肝静脉压力梯度(HVPG)呈负相关(rs =-0.302; p = 0.03)。miRNA-122水平升高与肝损伤和低HVPG相关。虽然miRNA-122水平不适合预测肝纤维化程度,但它们可能作为HIV/HCV合并感染患者门脉高压的指标。
Introduction of combined antiretroviral therapy (cART) has improved survival of HIV infected individuals, while the relative contribution of liver-related mortality increased. Especially in HIV/HCV-coinfected patients hepatic fibrosis and portal hypertension represent the main causes of liver-related morbidity and mortality. Circulating miRNA-122 levels are elevated in HIV patients and have been shown to correlate with severity of liver injury. However, the association of miRNA-122 levels and hepatic fibrosis and portal hypertension remains to be explored in HIV/HCV coinfection. From a total of 74 (31% female) patients with HIV/HCV coinfection were included. Serum levels of miRNA-122 were analyzed by quantitative polymerase chain reaction (PCR) and normalized to SV-40 spike-in RNA. Hepatic venous pressure gradient (HVPG) was measured in 52 (70%) patients and the fibrosis stage was determined in 63 (85%) patients using transient elastography. The levels of circulating miRNA-122 were increased in HIV/HCV coinfected patients and significantly correlated with the alanine aminotransferase (ALT) (rs = 0.438; p<0.001) and aspartate transaminase AST values (rs = 0.336; p = 0.003), but not with fibrosis stage (p = n.s.). Interestingly, miRNA-122 levels showed an inverse correlation with hepatic venous pressure gradient (HVPG) (rs = −0.302; p = 0.03). Elevated miRNA-122 levels are associated with liver injury, and with low HVPG. Though, miRNA-122 levels are not suitable to predict the degree of fibrosis, they might function as indicators for portal hypertension in HIV/HCV coinfected patients.
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