乙型肝炎相关慢加急性肝功能衰竭患者血清中miR-122的表达及其临床意义

Expression of miR-122 in serum of patients with HBV-related acute-on-chronic liver failure and the clinical significance

目的分析乙型肝炎(HBV)病毒感染相关慢加急性肝功能衰竭(HBV-ACLF)患者血清中miR-122表达水平与各临床指标是否有相关性,从而探讨血清中miR-122在评价HBV-ACLF疾病严重程度、诊断中的价值。方法收集山西医科大学第一医院就诊的HBV-ACLF患者血清样本49例、慢性乙型肝炎(CHB)患者血清样本30例及健康体检者的血清样本30例,通过实时荧光定量PCR检测各个样本miR-122的相对表达水平。以u6为内参,miR-122相对表达量用2-ΔCT表示。根据临床表现的严重程度将HBV-ACLF患者分为早期、中期和晚期组,比较不同组间miR-122表达水平的差异及其与生化指标的相关性。进一步通过非条件Logistic回归分析miR-122在HBV-ACLF病程进展中的作用,从而反映miR-122与疾病严重程度的关系。采用受试者工作特征曲线(ROC)评价血清中miR-122在HBV-ACLF诊断评估方面的价值。结果与健康体检者及CHB患者血清中miR-122的表达水平相比,HBV-ACLF患者血清中miR-122的表达水平上调(P<0.001),且在晚期HBV-ACLF患者血清中miR-122的表达水平较早期及中期显著上调(P<0.001、P=0.048)。HBV-ACLF患者血清miR-122表达水平的升高,与血清中总胆红素(TBil)的表达水平呈正相关(r=0.508、P<0.001);与PTA呈负相关(r=-0.797、P<0.001)。非条件Logistic回归分析结果显示对于HBV-ACLF早期而言,miR-122相对表达值2-ΔCT每增加一个单位,引起HBV-ACLF进展为中期的风险增加5.8%(95%CI:1.013~1.104),进展为晚期的风险增加13.0%(95%CI:1.034~1.235)。ROC分析结果显示,miR-122评价疾病的曲线下面积(AUC)为0.942(95%CI:0.903~0.982),灵敏度为83.7%,特异度为86.7%。结论血清中miR-122的表达水平可成为评价HBV-ACLF的严重程度及作为HBV-ACLF诊断的潜在生物标志。

Objective To investigate the relationship between the expression of miR-122 in HBV- related acute-on-chronic liver failure （HBV-ACLF） and clinical indicators, and to analyze the role of miR-122 in evaluating the severity and diagnosis of HBV-ACLF. Methods Serum samples from 49 patients with HBV- ACLF, 30 patients with chronic hepatitis B （CHB） and 30 healthy volunteers were collected from the First Affiated Hospital of Shanxi Medical University. The relative expression ofmiR-122 in each sample was detected by fluorescence real-time quantitative PCR. With the u6 as endogenous control, the relative expression of miR- 122 was expressed as 2-vCT. Patients with HBV-ACLF were divided into early stage, middle stage and late stage groups according to the severity of clinical manifestations. The levels of miR-122 expression between different groups were compared, and the correlation between the expression of miR-122 and biochemical markers were analyzed, respectively. Furthermore, the role of rniR-122 in the progression of HBV-ACLF was analyzed by Unconditional Logistic regression model, thus reflecting the association between miR-122 and disease severity. Receiver operating characteristic curve （ROC） was used to evaluate the value of serum miR-122 in the diagnosis of HBV-ACLF. Results The expression level ofmiR-122 in serum of patients with HBV-ACLF was significantly higher than those of healthy subjects and patients with CHB （P 〈 0.001）, and the level of miR-122 expression in advanced HBV-ACLF was significantly higher than those of the early and middle stages （P 〈 0.001, P = 0.048）. The serum level of miR-122 in patients With HBV-ACLF was positively correlated with the level of serum total bilirubin （TBil） （r = 0,508, P 〈 0.001） and negatively correlated with PTA （r =--0.797, P 〈 0.001）. Unconditional Logistic regression model showed that an increase of one unit of relative expression of miR-122 （2-~cT） was associated with 5.8% （95%CI： 1.013-1.104） increase in the risk of progression from HBV-ACLF early stage to middle stage and 13.0% （95%CI： 1.034-1.235） increase in the risk from early stage to late stage. The ROC analysis showed that the area under the curve （AUC） of disease diagnosis was 0.942 （95%CI： 0.903-0.982）, the sensitivity and the specificity were 83.7% and 86.7%, Conclusions The expression level of miR-122 in serum could be used as a biomarker for the diagnosis and the severity of HBV-ACLE