中性粒细胞与淋巴细胞比值对失代偿期肝硬化患者预后的评估价值
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摘要
目的探讨中性粒细胞与淋巴细胞比值(NLR)评估失代偿期肝硬化患者预后的价值。方法回顾性分析2013年1月-2016年12月安徽医科大学第三附属医院确诊的173例失代偿期肝硬化患者的临床资料,包括性别、年龄、病因、病史、入院后首次的实验室检查等资料。以死亡为终点事件,根据随访1年的疾病转归情况将所纳入的患者分为生存组(n=123)和死亡组(n=50)。分析影响预后的相关因素,并评估NLR对失代偿期肝硬化患者预后的预测价值。正态分布的计量资料两组间比较采用t检验;非正态分布的计量资料两组间比较采用Mann-Whitney U检验,计数资料两组间比较采用χ~2检验。采用Spearman相关分析评估两变量间的相关性。对相关变量行Cox单因素分析,采用多因素Cox风险比例模型(enter法)分析独立影响因素。绘制受试者工作特征曲线(ROC曲线),计算ROC曲线下面积(AUC),并根据约登指数确定最佳临界值。运用Kaplan-Meier生存曲线分析不同NLR患者的1年生存率,并采用log-rank检验进行比较。结果死亡组患者的NLR、Child-Turcotte-Pugh(CTP)评分及终末期肝病模型(MELD)评分与生存组比较均显著升高(U值分别为4660. 0、4994. 5,t=-9. 209,P值均<0. 001)。NLR与CTP评分和MELD评分均呈正相关(r值分别为0. 363、0. 410,P值均<0. 001)。NLR、MELD评分预测患者1年预后最佳临界值分别为3. 52、14. 26,AUC分别为0. 758、0. 854,二者联合其AUC可增加至0. 863。生存分析结果显示高水平NLR组(NLR≥3. 52)患者生存率明显低于低水平NLR组(NLR <3. 52)(χ~2=36. 602,P <0. 001)。多因素Cox回归分析提示,NLR≥3. 52是预测患者1年死亡的独立危险因素。结论 NLR对失代偿期肝硬化患者1年预后有较好的预测价值。
Objective To investigate the value of neutrophil-lymphocyte ratio( NLR) in predicting the prognosis of patients with decompensated cirrhosis. Methods A retrospective analysis was performed for the clinical data of 173 patients who were diagnosed with decompensated cirrhosis in The Third Affiliated Hospital of Anhui Medical University from January 2013 to December 2016,including sex,age,etiology,medical history,and first laboratory examination after admission. With death as the outcome event,these patients were divided into survival group and death group according to the outcome of the disease at 1-year follow-up. The influencing factors for prognosis were analyzed,and the value of NLR in predicting the prognosis of patients with decompensated cirrhosis were evaluated. The t-test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was performed to investigate the correlation between two variables. A univariate Cox analysis was performed for related variables,and the multivariate Cox proportional hazards model was used to identify independent influencing factors.The receiver operating characteristic( ROC) curve was plotted and the area under the ROC curve( AUC) was calculated; the optimal cut-off value was determined according to the optimal Youden index. The Kaplan-Meier survival analysis was performed to compare the 1-year survival rate of patients with different NLR values,and the log-rank test was used for comparison. Results Of all 173 patients,50 died and 123 survived within the 1-year follow-up. The death group had significantly higher NLR,Child-Turcotte-Pugh( CTP) score,and Model for End-Stage Liver Disease( MELD) score than the survival group( U = 4660. 0,4994. 5,and t =-9. 209,all P < 0. 001).NLR was positively correlated with CTP score and MELD score( r = 0. 363 and 0. 410,both P < 0. 001). The optimal cut-off values of NLR and MELD score in predicting 1-year prognosis were 3. 52 and 14. 26,respectively,with AUCs of 0. 758 and 0. 854,respectively;the combination of NLR and MELD score had an increased AUC of 0. 863. The survival analysis showed that the high-NLR group( NLR≥3. 52) had a significantly lower survival rate than the low-NLR group( NLR < 3. 52)( χ~2= 36. 602,P < 0. 001). The multivariate Cox regression analysis showed that NLR≥3. 52 was an independent risk factor for death within 1 year. Conclusion NLR has a good value in predicting the 1-year prognosis of patients with decompensated cirrhosis.
Objective To investigate the value of neutrophil-lymphocyte ratio( NLR) in predicting the prognosis of patients with decompensated cirrhosis. Methods A retrospective analysis was performed for the clinical data of 173 patients who were diagnosed with decompensated cirrhosis in The Third Affiliated Hospital of Anhui Medical University from January 2013 to December 2016,including sex,age,etiology,medical history,and first laboratory examination after admission. With death as the outcome event,these patients were divided into survival group and death group according to the outcome of the disease at 1-year follow-up. The influencing factors for prognosis were analyzed,and the value of NLR in predicting the prognosis of patients with decompensated cirrhosis were evaluated. The t-test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was performed to investigate the correlation between two variables. A univariate Cox analysis was performed for related variables,and the multivariate Cox proportional hazards model was used to identify independent influencing factors.The receiver operating characteristic( ROC) curve was plotted and the area under the ROC curve( AUC) was calculated; the optimal cut-off value was determined according to the optimal Youden index. The Kaplan-Meier survival analysis was performed to compare the 1-year survival rate of patients with different NLR values,and the log-rank test was used for comparison. Results Of all 173 patients,50 died and 123 survived within the 1-year follow-up. The death group had significantly higher NLR,Child-Turcotte-Pugh( CTP) score,and Model for End-Stage Liver Disease( MELD) score than the survival group( U = 4660. 0,4994. 5,and t =-9. 209,all P < 0. 001).NLR was positively correlated with CTP score and MELD score( r = 0. 363 and 0. 410,both P < 0. 001). The optimal cut-off values of NLR and MELD score in predicting 1-year prognosis were 3. 52 and 14. 26,respectively,with AUCs of 0. 758 and 0. 854,respectively;the combination of NLR and MELD score had an increased AUC of 0. 863. The survival analysis showed that the high-NLR group( NLR≥3. 52) had a significantly lower survival rate than the low-NLR group( NLR < 3. 52)( χ~2= 36. 602,P < 0. 001). The multivariate Cox regression analysis showed that NLR≥3. 52 was an independent risk factor for death within 1 year. Conclusion NLR has a good value in predicting the 1-year prognosis of patients with decompensated cirrhosis.
引文
[1]BERNARDI M,CARACENI P.Novel perspectives in the management of decompensated cirrhosis[J].Nat Rev Gastroenterol Hepatol,2018,15(12):753-764.
[2]European Association for the Study of the Liver.EASL clinical practice guidelines for the management of patients with decompensated cirrhosis[J].J Hepatol,2018,69(2):406-460.
[3]KAMATH PS,WIESNER RH,MALINCHOC M,et al.A model to predict survival in patients with end-stage liver disease[J].Hepatology,2001,33(2):464-470.
[4]PENG Y,QI X,GUO X.Child-Pugh versus MELD score for the assessment of prognosis in liver cirrhosis:A systematic review and Meta-analysis of observational studies[J].Medicine(Baltimore),2016,95(8):e2877.
[5]DURAND F,VALLA D.Assessment of the prognosis of cirrhosis:Child-Pugh versus MELD[J].J Hepatol,2005,42(Suppl 1):s100-s107.
[6]LIPPI G,TARGHER G,MONTAGNANA M,et al.Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients[J].Arch Pathol Lab Med,2009,133(4):628-632.
[7]IMTIAZ F,SHAFIQUE K,MIRZA SS,et al.Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population[J].Int Arch Med,2012,5(1):2.
[8]FAN X,DENG H,WANG X,et al.Association of red blood cell distribution width with severity of hepatitis B virus-related liver diseases[J].Clin Chim Acta,2018,482:155-160.
[9]FAN Z,ENQIANG C,YAO DL,et al.Neutrophil-lymphocyte ratio predicts short term mortality in patients with hepatitis B virus-related acute-on-chronic liver failure treated with an artificial liver support system[J].PLo S One,2017,12(4):e0175332.
[10]CHEN L,LOU Y,CHEN Y,et al.Prognostic value of the neutrophil-to-lymphocyte ratio in patients with acute-on-chronic liver failure[J].Int J Clin Pract,2014,68(8):1034-1040.
[11]HU Z,SUN Y,WANG Q,et al.Red blood cell distribution width is a potential prognostic index for liver disease[J].Clin Chem Lab Med,2013,51(7):1403-1408.
[12]PUGH RN,MURRAY-LYON IM,DAWSON JL,et al.Transection of the oesophagus for bleeding oesophageal varices[J].Br J Surg,1973,60(8):646-649.
[13]D'AMICO G,GARCIA-TSAO G,PAGLIARO L.Natural history and prognostic indicators of survival in cirrhosis:A systematic review of 118 studies[J].J Hepatol,2006,44(1):217-231.
[14]BIYIK M,UCAR R,SOLAK Y,et al.Blood neutrophil-tolymphocyte ratio independently predicts survival in patients with liver cirrhosis[J].Eur J Gastroenterol Hepatol,2013,25(4):435-441.
[15]ZHANG H,SUN Q,MAO W,et al.Neutrophil-to-lymphocyte ratio predicts early mortality in patients with hbv-related decompensated cirrhosis[J].Gastroenterol Res Pract,2016,2016:4394650.
[16]ZHANG L,CHEN W,SHENG YJ,et al.Value of Model for End-Stage Liver Disease score combined with neutrophillymphocyte ratio in predicting the short-term prognosis of patients with HBV-related acute-on-chronic liver failure[J].J Clin Hepatol,2018,34(3):553-557.(in Chinese)张丽,陈文,盛云健,等.MELD评分联合中性粒细胞/淋巴细胞比值对HBV相关慢加急性肝衰竭短期预后的预测价值[J].临床肝胆病杂志,2018,34(3):553-557.
[17]LI XH,YANG RF,JIN Q,et al.Change in neutrophil-lymphocyte ratio during antiviral therapy for HBe Ag-positive chronic hepatitis B patients and its predictive value[J].Chin JHepatol,2018,26(1):60-62.(in Chinese)李晓鹤,杨瑞锋,金茜,等.HBe Ag阳性慢性乙型肝炎患者干扰素抗病毒治疗中中性粒细胞淋巴细胞比值的变化及预测价值[J].中华肝脏病杂志,2018,26(1):60-62.
[18]CLARIA J,STAUBER RE,COENRAAD MJ,et al.Systemic inflammation in decompensated cirrhosis:Characterization and role in acute-on-chronic liver failure[J].Hepatology,2016,64(4):1249-1264.
[19]GIRON-GONZALEZ JA,MARTINEZ-SIERRA C,RODRIGU-EZ-RAMOS C,et al.Implication of inflammation-related cytokines in the natural history of liver cirrhosis[J].Liver Int,2004,24(5):437-445.
[20]LIN L,YANF F,WANG Y,et al.Prognostic nomogram incorporating neutrophil-to-lymphocyte ratio for early mortality in decompensated liver cirrhosis[J].Int Immunopharmacol,2018,56:58-64.
[21]MIYAMOTO M,PRAUSE O,SJOSTRAND M,et al.Endogenous IL-17 as a mediator of neutrophil recruitment caused by endotoxin exposure in mouse airways[J].J Immunol,2003,170(9):4665-4672.
[22]FOCK RA,BLATT SL,BEUTLER B,et al.Study of lymphocyte subpopulations in bone marrow in a model of protein-energy malnutrition[J].Nutrition,2010,26(10):1021-1028.
[2]European Association for the Study of the Liver.EASL clinical practice guidelines for the management of patients with decompensated cirrhosis[J].J Hepatol,2018,69(2):406-460.
[3]KAMATH PS,WIESNER RH,MALINCHOC M,et al.A model to predict survival in patients with end-stage liver disease[J].Hepatology,2001,33(2):464-470.
[4]PENG Y,QI X,GUO X.Child-Pugh versus MELD score for the assessment of prognosis in liver cirrhosis:A systematic review and Meta-analysis of observational studies[J].Medicine(Baltimore),2016,95(8):e2877.
[5]DURAND F,VALLA D.Assessment of the prognosis of cirrhosis:Child-Pugh versus MELD[J].J Hepatol,2005,42(Suppl 1):s100-s107.
[6]LIPPI G,TARGHER G,MONTAGNANA M,et al.Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients[J].Arch Pathol Lab Med,2009,133(4):628-632.
[7]IMTIAZ F,SHAFIQUE K,MIRZA SS,et al.Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population[J].Int Arch Med,2012,5(1):2.
[8]FAN X,DENG H,WANG X,et al.Association of red blood cell distribution width with severity of hepatitis B virus-related liver diseases[J].Clin Chim Acta,2018,482:155-160.
[9]FAN Z,ENQIANG C,YAO DL,et al.Neutrophil-lymphocyte ratio predicts short term mortality in patients with hepatitis B virus-related acute-on-chronic liver failure treated with an artificial liver support system[J].PLo S One,2017,12(4):e0175332.
[10]CHEN L,LOU Y,CHEN Y,et al.Prognostic value of the neutrophil-to-lymphocyte ratio in patients with acute-on-chronic liver failure[J].Int J Clin Pract,2014,68(8):1034-1040.
[11]HU Z,SUN Y,WANG Q,et al.Red blood cell distribution width is a potential prognostic index for liver disease[J].Clin Chem Lab Med,2013,51(7):1403-1408.
[12]PUGH RN,MURRAY-LYON IM,DAWSON JL,et al.Transection of the oesophagus for bleeding oesophageal varices[J].Br J Surg,1973,60(8):646-649.
[13]D'AMICO G,GARCIA-TSAO G,PAGLIARO L.Natural history and prognostic indicators of survival in cirrhosis:A systematic review of 118 studies[J].J Hepatol,2006,44(1):217-231.
[14]BIYIK M,UCAR R,SOLAK Y,et al.Blood neutrophil-tolymphocyte ratio independently predicts survival in patients with liver cirrhosis[J].Eur J Gastroenterol Hepatol,2013,25(4):435-441.
[15]ZHANG H,SUN Q,MAO W,et al.Neutrophil-to-lymphocyte ratio predicts early mortality in patients with hbv-related decompensated cirrhosis[J].Gastroenterol Res Pract,2016,2016:4394650.
[16]ZHANG L,CHEN W,SHENG YJ,et al.Value of Model for End-Stage Liver Disease score combined with neutrophillymphocyte ratio in predicting the short-term prognosis of patients with HBV-related acute-on-chronic liver failure[J].J Clin Hepatol,2018,34(3):553-557.(in Chinese)张丽,陈文,盛云健,等.MELD评分联合中性粒细胞/淋巴细胞比值对HBV相关慢加急性肝衰竭短期预后的预测价值[J].临床肝胆病杂志,2018,34(3):553-557.
[17]LI XH,YANG RF,JIN Q,et al.Change in neutrophil-lymphocyte ratio during antiviral therapy for HBe Ag-positive chronic hepatitis B patients and its predictive value[J].Chin JHepatol,2018,26(1):60-62.(in Chinese)李晓鹤,杨瑞锋,金茜,等.HBe Ag阳性慢性乙型肝炎患者干扰素抗病毒治疗中中性粒细胞淋巴细胞比值的变化及预测价值[J].中华肝脏病杂志,2018,26(1):60-62.
[18]CLARIA J,STAUBER RE,COENRAAD MJ,et al.Systemic inflammation in decompensated cirrhosis:Characterization and role in acute-on-chronic liver failure[J].Hepatology,2016,64(4):1249-1264.
[19]GIRON-GONZALEZ JA,MARTINEZ-SIERRA C,RODRIGU-EZ-RAMOS C,et al.Implication of inflammation-related cytokines in the natural history of liver cirrhosis[J].Liver Int,2004,24(5):437-445.
[20]LIN L,YANF F,WANG Y,et al.Prognostic nomogram incorporating neutrophil-to-lymphocyte ratio for early mortality in decompensated liver cirrhosis[J].Int Immunopharmacol,2018,56:58-64.
[21]MIYAMOTO M,PRAUSE O,SJOSTRAND M,et al.Endogenous IL-17 as a mediator of neutrophil recruitment caused by endotoxin exposure in mouse airways[J].J Immunol,2003,170(9):4665-4672.
[22]FOCK RA,BLATT SL,BEUTLER B,et al.Study of lymphocyte subpopulations in bone marrow in a model of protein-energy malnutrition[J].Nutrition,2010,26(10):1021-1028.