血清NGAL和Cys C对慢加急性肝衰竭患者并发肝肾综合征早期诊断价值研究

doi:10.3969/j.issn.1672-5069.2018.04.023

摘要/Abstract

摘要： 目的研究血清中性粒细胞明胶酶相关载脂蛋白（NGAL）和光抑素C（Cys-C）诊断慢加急性肝衰竭（ACLF）患者并发肝肾综合征（HRS）的价值。方法 2010年1月~2017年1月收治的204例ACLF患者,并发HRS 58例。采用固相夹心酶联免疫吸附法检测血清NGAL,常规检测血清Cys-C、β2-微球蛋白（β2-MG）。绘制受试者工作特征曲线（ROC）评估血清指标诊断ACLF患者并发HRS的价值。结果 HRS与非HRS患者在性别、病程、BMI、糖尿病、血小板计数、血K⁺、平均动脉压方面比较无显著性差异（P>0.05）,两组在年龄、高血压、冠心病、白细胞计数、白蛋白、蛋白尿、血尿素氮、血Na⁺和Child-Pugh评分方面存在明显差异（P<0.05）;HRS患者NGAL、Cys-C、sCr、β2-MG、BUN水平分别为（64.1±18.4） ng/mL、（3.1±1.1） mg/L、（165.8±25.7） mol/L、（6.3±2.1） mg/L、（12.6±4.3） mmol/L,显著高于无HRS组【（11.5±2.3） ng/mL、（1.2±0.4） mg/L、（62.6±11.4） mol/L、（2.7±1.2） mg/L、（4.1±1.5） mmol/L,P<0.05】;HRS组患者肝损伤程度显著重于无HRS组（P<0.05）;血清 NGAL和Cys-C诊断ACLF并发HRS的敏感度和准确度分别为（89.6%）和（92.1%）,和85.9%和95.4%,显著高于血清sCr、β2-MG或BUN,而NGAL联合Cys-C检测诊断的敏感度和准确度分别为92.1%和96.2%,明显优于血清NGAL或Cys-C单独检测。结论在ACLF患者中年龄越大,并发HRS的机会越大,病情重的患者血清NGAL和Cys-C水平升高,应用它们联合诊断ACLF患者并发HRS的效能较好,值得进一步研究。

关键词: 慢加急性肝衰竭, 肝肾综合征, 中性粒细胞明胶酶相关载脂蛋白, 光抑素C, 诊断

Abstract: Objective To investigate the efficacy of serum neutrophil gelatinase associated apolipoprotein (NGAL) and cystatin C （Cys C） in early diagnosis of hepatorenal syndrome（HRS） in patients with acute on chronic liver failure （ACLF）. Methods The clinical data of 204 patients with acute on chronic liver failure in our hospital between January 2010 and January 2017 were retrospectively analyzed,and we found 58 patients having HRS. Serum NGAL,Cys-C, creatinine（Cr）,β2-microglobulin（β2-MG） and urea nitrogen（BUN） were assayed. The diagnostic value of serum parameters in ACLF patients were investigated by the area under the receiver operator characteristic curve （AUROC）. Results The gender,body mass index,course of disease, diabetes,platelet count,blood K⁺,mean arterial pressure were not significantly different between patients with HRS and those without （P>0.05）,while there were obvious differences as respect to the age,hypertension,coronary heart disease,white blood cell count,albumin,proteinuria,blood urea nitrogen, blood Na⁺ and Child-Pugh score between the two groups （P<0.05）;serum NGAL,Cys-C,sCr,β2-MG and BUN levels in patients with HRS were（64.1±18.4） ng/mL,（3.1±1.1） mg/L,（165.8±25.7） μmol/L,（6.3±2.1） mg/L and （12.6±4.3） mmol/L,significantly higher than （11.5±.3） ng/mL,（1.2±0.4） mg/L,（62.6±11.4） μmol/L,（2.7±1.2） mg/L and（4.1±1.5） mmol/L in patients without HRS（P<0.05）;serum parameters of liver functions such as serum bilirubin,and coagulation index in patients with HRS were more severe than those in patients without HRS （P<0.05）;the sensitivity and accuracyof NGAL and Cys-C in diagnosing HRS were 89.6% and 92.1%,and 85.9% and 95.4%,respectively, significantly higher than those by serum Cr,β2-MG or BUN,and the sensitivity and accuracy of combination of NGAL and Cys-C were 92.1% and 96.7%,respectively,also significantly higher than those by NGAL or Cys-C alone. Conclusion The probability of hepatorenal syndrome occurrence in ACLF patients with old age is increasing,and the application of serum NGAL and Cys C in the early diagnosis and prediction of HRS in patients with ACLF is promising, which warrants further clinically observation.

Key words: Acute on chronic liver failure, Hepatorenal syndrome, Neutrophil gelatinase associated apolipoprotein, Cystatin C, Diagnosis

李英宽, 索明果, 高聪聪, 魏伦. 血清NGAL和Cys C对慢加急性肝衰竭患者并发肝肾综合征早期诊断价值研究[J]. 实用肝脏病杂志, 2018, 21(4): 577-580.

Li Yingkuan, Suo Mingguo, Gao Congcong, et al. Efficacy of serum neutrophil gelatinase associated apolipoprotein and cystatin C in early diagnosis of hepatorenal syndrome in patients with acute on chronic liver failure[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(4): 577-580.

参考文献

[1] Stelmach-Goldys A,Czarkowska-Paczek B,Wyczalkowska-Toma-sik A,et al. Serum cystatin C and serum and urine NGAL in the kidney function assessment of patients with MGUS. Eur J Haematol,2015,94(2):162-168.
[2] Ermetici F,Filopanti M,Verga U,et al.Estimated glomerular filtration rate by serum cystatin C correlates with cardiometa-bolic parameters in patients with primary hyperparathyroidism. Eur J Endocrinol,2015,173(4):441.
[3] 赵萍,翟玉峰,张怀宏. 血清甲胎蛋白和凝血酶原活动度水平对慢加急性肝衰竭患者预后的预测价值研究. 实用肝脏病杂志,2017,20(2):230-231.
[4] Li H,Xia Q,Zeng B,et al.Submassive hepatic necrosis distinguishes HBV-associated acute on chronic liver failure from cirrhotic patients with acute decompensation. J Hepatol,2015,63(1):50-59.
[5] Woldu SL,Matulay JT,Silva MV,et al.Serum cystatin C as a novel marker to differentiate pseudoazotemia in the setting of intraperitoneal urine extravasation. Urology,2015,85(4):918-920.
[6] Treiber M,Balon B P,Gorenjak M.A new serum cystatin C formula for estimating glomerular filtration rate in newborns. Pediatr Nephrol,2015,30(8):1297-1305.
[7] 吴军. 特利加压素与托拉塞米治疗失代偿期肝硬化并发肝肾综合征患者疗效比较. 实用肝脏病杂志,2015,18(1):78-79.
[8] Seetlani NK,Memon AR,Iftikhar F,et al.Hepatorenal syndrome in patients with cirrhosis of liver according to 2007 international ascites club criteria. J Ayub Med Coll,2016,28(3):578-581.
[9] Yang Y,Zhao X,Tang X,et al.Comparison of serum cystatin C and creatinine level changes for prognosis of patients after peripheral arterial angiography. Angiology,2015,66(8):766-773.
[10] 蔡均均,周静,韩涛,等. 血清胱抑素C对肝硬化患者并发急性肾损伤的诊断价值. 中华肝脏病杂志,2017,25(5):157-158.
[11] Gustot T,Fernandez J,Garcia E,et al.Clinical course of acute-on-chronic liver failure syndrome and effects on prognosis. Hepatology,2015,62(1):243-252.
[12] Shi Y,Yang Y,Hu Y,et al.Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults. Hepatology,2015,62(1):232.
[13] Bernsmeier C,Pop OT,Singanayagam A,et al.Patients with acute-on-chronic liver failure have increased numbers of regulatory immune cells expressing the receptor tyrosine kinase MERTK. Gastroenterology,2015, 48(3):603.
[14] Anna S,Anna T,Mike S,et al.Factors limiting usefulness of serum and urinary NGAL as a marker of acute kidney injury in preterm newborns. Ren Fail,2015,37(3):1-7.
[15] 蒋一航,王玮,胡小鹏,等. NGAL与Cys c对于肾移植术后早期肾功能恢复的预测作用. 中华医学杂志,2015,95(2):112-115.
[16] Durand F,Graupera I,Ginès P,et al.Pathogenesis of hepatorenal syndrome:Implications for therapy. Am J Kidney Dis,2015,67(2):318-328.
[17] Hoková L,Franekova J,Málek I,et al.Comparison of cystatin C and NGAL in early diagnosis of acute kidney injury after heart transplantation. Ann Transpl,2016,21(22):329.
[18] Herbert C,Patel M,Nugent A,et al.Serum cystatin C as an early marker of neutrophil gelatinase-associated lipocalin-positive acute kidney injury resulting from cardiopulmonary bypass in infants with congenital heart disease. Congenit Heart Dis,2015,10(4):180-188.
[19] Ginès P.Management of hepatorenal syndrome in the era of acute-on-chronic liver failure:Terlipressin and beyond. Gastroenterology,2016,150(7):1525.
[20] Cavallin M,Piano S,Romano A,et al.Terlipressin given by continuous intravenous infusion versus intravenous boluses in the treatment of hepatorenal syndrome:A randomized controlled study. Hepatology,2016,63(3):983.