肝硬化患者外周血清HIF-1α、HO-1定量检测的临床价值

Clinical significance of circulating hypoxia inducible factor-1α and hemeoxygenase-1 in patients with liver cirrhosis

目的 探讨血清中缺氧诱导因子1α（HIF-1α）、血红素加氧酶1（HO-1）作为肝硬化无创诊断的临床价值.方法 收集2012年5月至2013年5月复旦大学附属中山医院诊治的34例不同阶段肝硬化患者及10名健康对照者的血清,以酶联免疫吸附法（ELISA）定量检测其中HIF-1α、HO-1表达水平,并利用受试者工作曲线（ROC）分析其临床意义.结果 肝硬化患者血清中HIF-1 α及HO-1水平均明显高于健康对照组[（10.99 ±0.24）比（5.79±0.84） μg/L,（63.04±1.87）比（16.35 ±2.07） μg/L,均P＜0.01].但在肝硬化患者Child-Pugh A、B、C3级之间,HIF-1α、HO-1水平差异均无统计学意义（均P＞0.05）.HIF-1 α与HO-1表达水平呈线性关系（P＜0.01）.在有无再出血及门静脉血栓形成的肝硬化患者中HIF-1α的表达差异均有统计学意义;在有无再出血的肝硬化患者中H0-1表达差异亦有统计学意义（均P＜0.05）.HIF-1α和HO-1诊断早期肝硬化的ROC曲线下面积分别为0.894和0.994.将HIF-1 α临界值定为9.45 μg/L,敏感度和特异度分别为91.2％和90.0％.以31.86 μg/L作为HO-1的临界值,敏感度和特异度分别为97.1％和100％.结论 外周血清HIF-1 α、HO-1水平是肝硬化患者病情评估的独立预测因子,可联合或单独用于肝硬化无创诊断.

Objective To explore the levels of circulating hypoxia inducible factor-1α （HIF-1α） and hemeoxygenase-1 （HO-1） in liver cirrhosis and to explore their diagnostic values as noninvasive methods.Methods The levels of circulating HIF-lα and HO-1 were quantitatively detected in 34 patients with liver cirrhosis and 10 healthy controls by ELISA from May 2012 to May 2013.The diagnostic values were analyzed by ROC curve and their correlation with clinicopathological characters were also compared.Results The serum levels of HIF-lα and HO-1 were significantly higher than those in healthy controls （（10.99 ±0.24） vs（5.79 ±0.84） μg/L,（63.04 ± 1.87） vs （16.35 ±2.07） μg/L,both P ＜0.01）.No significant difference existed among Child-Pugh classification.The expressions of HIF-1α and HO-1 had a linear correlation between each other,and closely related with rebleeding and portal thrombosis during a oneyear follow-up （all P ＜ 0.05）.The area under ROC curve of HIF-lα and HO-1 was 0.894 and 0.994 respectively.With 9.45 μg/L as a critical point for HIF-1α,the diagnosis of liver cirrhosis might be predicted with a positive predictive value of 91.2％.And HO-1 ＞ 31.86 μg/L predicted the diagnosis of liver cirrhosis with a sensitivity of 97.1％ and a specificity of 100％.Conclusion The serum levels of HIF1α and HO-1 may serve as useful molecular markers for a noninvasive diagnosis of liver cirrhosis.