构建诺模图模型预测肝硬化食管胃底静脉曲张出血的风险

doi:10.3877/cma.j.issn.2095-2015.2024.04.009

目的

评估HBV相关肝硬化患者食管胃底静脉曲张出血（EVGB）的风险因素，以构建预测EVGB风险的诺模图模型。

方法

以2019年1月至2022年1月南通大学附属南通第三医院收治的300例HBV相关肝硬化患者为研究对象，采用单、多变量Logistic回归分析筛选EVGB的风险因素并构建诺模图。通过受试者特征（ROC）的曲线下面积（AUC），评估模型对EVGB风险的识别能力。绘制校准曲线衡量模型预测风险与实际观测风险之间的一致性。

结果

共131例（43.7%）患者有EVGB史，单、多变量Logistic回归分析显示，腹水（OR=6.186，95% CI 3.286～11.644，P<0.001）、血小板计数（OR=0.983，95% CI 0.978～0.989，P<0.001）、血清白蛋白值（OR=0.963，95% CI 0.928～0.999，P=0.042）以及血糖水平（OR=1.093，95% CI 1.003～1.190，P=0.042）是EVGB的独立风险因素。基于以上变量构建预测肝硬化患者EVGB风险的诺模图，该模型AUC值为0.826（95% CI 0.780～0.872），提示判别能力良好。校准曲线显示模型预测风险与发生EGVB的实际风险之间具有高度一致性。

结论

腹水、血小板计数、血清白蛋白和血糖水平与肝硬化EGVB显著相关，基于这些变量构建的诺模图模型对EGVB风险具有良好的预测能力，可能有助于指导医护人员开展精准预防和临床干预。

关键词: 肝硬化, 食管胃底静脉曲张, 出血, 风险因素, 预测, 诺模图

Objective

To evaluate the risk factors of esophagogastric variceal bleeding (EVGB) for patients with hepatitis B virus (HBV)-related cirrhosis, and to construct a nomogram model to predict the risk of EVGB.

Methods

A total of 300 HBV-related cirrhotic patients admitted to Nantong Third Hospital Affiliated to Nantong University from January 2019 to January 2022 were selected as the study objects. The independent risk factors of EVGB were determined by the univariate and multivariate Logistic regression analysis, and a nomogram for predicting the risk of EVGB was constructed. The discriminative ability of the nomogram model for high-risk individual with EVGB was evaluated using the area under curve (AUC) of receiver operation characteristics (ROC) curve. Calibration curves were plotted to compare the consistency between the predicted risk and actual risk.

Results

A total of 131 patients (43.7%) had a history of EVGB, and the results of univariate and multivariate Logistic regression analysis revealed that ascites (OR=6.186, 95% CI: 3.286-11.644, P<0.001), platelet count (OR=0.983, 95% CI: 0.978-0.989, P<0.001), serum albumin (OR=0.963, 95% CI: 0.928-0.999, P=0.042) and blood glucose level (OR=1.093, 95% CI: 1.003-1.190, P=0.042) were independent risk factors for EVGB. Based on the above variables, a nomogram was constructed to predict the risk of EVGB in cirrhotic patients. The AUC value was 0.826 (95% CI: 0.780-0.872), suggesting a good predictive ability. The calibration curve showed a high level of consistency between the predicted risk and the actual risk.

Conclusion

Ascites, platelet count, serum albumin and blood glucose level are significantly correlated with the risk of EGVB in liver cirrhosis. The nomogram based on these variables has good predictive ability for the risk of EGVB, and it may help medical staffs make prevention strategy and clinical interventions.

Key words: Liver cirrhosis, Esophagogastric varices, Bleeding, Risk factors, Prediction, Nomogram

表1 研究人群基线特征的比较

基线特征	食管胃底静脉曲张破裂出血		统计量	P值
基线特征	无(n=169)	有(n=131)	统计量	P值
年龄[例(%)]			4.167	0.041
<55岁	100(59.2)	62(47.3)
≥55岁	69(40.8)	69(52.7)
性别[例(%)]			0.639	0.424
男	122(72.2)	89(67.9)
女	47(27.8)	42(32.1)
吸烟史[例(%)]	57(33.7)	42(32.1)	0.093	0.761
酗酒史[例(%)]	52(30.8)	33(25.2)	1.131	0.288
高血压[例(%)]	27(16.0)	27(20.6)	1.074	0.300
糖尿病[例(%)]	18(10.7)	15(11.5)	0.048	0.826
腹水[例(%)]			16.348	<0.001
无	147(87.0)	67(51.1)
有	22(13.0)	64(48.9)
WBC计数(×10⁹/L,IP25-P75)	5.2(3.9~7.4)	4.4(3.0~6.3)	3.368	0.001
PLT计数(×10⁹/L,IP25-P75)	142.0(102.0~170.0)	82.0(55.0~113.0)	7.974	< 0.001
血红蛋白(g/dL,±s)	12.5±3.1	11.0±3.2	4.111	< 0.001
INR(±s)	1.09±0.18	1.18±0.19	4.328	< 0.001
PT(S,IP25-P75)	12.0(11.1~15.6)	14.4(12.0~17.9)	4.089	< 0.001
ALT(U/L,IP25-P75)	41.0(25.0~97.0)	42.0(28.0~90.0)	0.456	0.648
AST(U/L,IP25-P75)	37.0(27.0~66.0)	42.0(29.0~61.0)	0.798	0.425
总胆红素(μmol/L,IP25-P75)	22.0(16.2~30.8)	27.3(18.8~36.4)	3054	0.002
血清白蛋白(g/L,±s)	38.3±7.9	34.5±8.0	4.189	< 0.001
γ-GT(U/L,IP25-P75)	40.0(19.0~100.0)	48.0(23.0~97.0)	0.837	0.402
ALP(U/L,IP25-P75)	88.0(68.0~120.0)	97.0(72.0~127.0)	1.580	0.114
血肌酐(μmol/L,IP25-P75)	69.6(59.7~83.9)	69.6(59.2~83.1)	0.641	0.521
尿素氮(mmol/L,IP25-P75)	4.8(4.0~6.9)	5.7(4.1~9.3)	1.953	0.053
血钠(mmol/L,±s)	139.5±3.3	138.7±3.4	2.040	0.042
血钾(mmol/L,±s)	3.9±0.6	3.9±0.7	0.313	0.754
血糖(mmol/L,IP25-P75)	5.5(5.0~6.7)	6.0(5.1~7.8)	2.469	0.014
Child-pugh分级[例(%)]			18.969	< 0.001
A	106(62.7)	50(38.2)
B	58(34.3)	70(53.4)
C	5(3.0)	11(8.4)

表1 研究人群基线特征的比较

基线特征	食管胃底静脉曲张破裂出血		统计量	P值
基线特征	无(n=169)	有(n=131)	统计量	P值
年龄[例(%)]			4.167	0.041
<55岁	100(59.2)	62(47.3)
≥55岁	69(40.8)	69(52.7)
性别[例(%)]			0.639	0.424
男	122(72.2)	89(67.9)
女	47(27.8)	42(32.1)
吸烟史[例(%)]	57(33.7)	42(32.1)	0.093	0.761
酗酒史[例(%)]	52(30.8)	33(25.2)	1.131	0.288
高血压[例(%)]	27(16.0)	27(20.6)	1.074	0.300
糖尿病[例(%)]	18(10.7)	15(11.5)	0.048	0.826
腹水[例(%)]			16.348	<0.001
无	147(87.0)	67(51.1)
有	22(13.0)	64(48.9)
WBC计数(×10⁹/L,IP25-P75)	5.2(3.9~7.4)	4.4(3.0~6.3)	3.368	0.001
PLT计数(×10⁹/L,IP25-P75)	142.0(102.0~170.0)	82.0(55.0~113.0)	7.974	< 0.001
血红蛋白(g/dL,±s)	12.5±3.1	11.0±3.2	4.111	< 0.001
INR(±s)	1.09±0.18	1.18±0.19	4.328	< 0.001
PT(S,IP25-P75)	12.0(11.1~15.6)	14.4(12.0~17.9)	4.089	< 0.001
ALT(U/L,IP25-P75)	41.0(25.0~97.0)	42.0(28.0~90.0)	0.456	0.648
AST(U/L,IP25-P75)	37.0(27.0~66.0)	42.0(29.0~61.0)	0.798	0.425
总胆红素(μmol/L,IP25-P75)	22.0(16.2~30.8)	27.3(18.8~36.4)	3054	0.002
血清白蛋白(g/L,±s)	38.3±7.9	34.5±8.0	4.189	< 0.001
γ-GT(U/L,IP25-P75)	40.0(19.0~100.0)	48.0(23.0~97.0)	0.837	0.402
ALP(U/L,IP25-P75)	88.0(68.0~120.0)	97.0(72.0~127.0)	1.580	0.114
血肌酐(μmol/L,IP25-P75)	69.6(59.7~83.9)	69.6(59.2~83.1)	0.641	0.521
尿素氮(mmol/L,IP25-P75)	4.8(4.0~6.9)	5.7(4.1~9.3)	1.953	0.053
血钠(mmol/L,±s)	139.5±3.3	138.7±3.4	2.040	0.042
血钾(mmol/L,±s)	3.9±0.6	3.9±0.7	0.313	0.754
血糖(mmol/L,IP25-P75)	5.5(5.0~6.7)	6.0(5.1~7.8)	2.469	0.014
Child-pugh分级[例(%)]			18.969	< 0.001
A	106(62.7)	50(38.2)
B	58(34.3)	70(53.4)
C	5(3.0)	11(8.4)

表2 多变量Logistic回归分析肝硬化食管胃底静脉曲张破裂出血的风险因素

因素	β	SE	Wald	OR	95% CI	P
年龄(≥55岁vs <55岁)	0.089	0.303	0.087	1.076	0.597~1.941	0.807
腹水(有vs无)	1.822	0.323	31.880	6.186	3.286~11.644	<0.001
WBC计数	-0.056	0.051	1.184	0.933	0.845~1.030	0.171
PLT计数	-0.017	0.003	32.252	0.983	0.978~0.989	<0.001
血红蛋白	-0.057	0.065	0.751	0.953	0.839~1.083	0.462
INR	-1.008	1.189	0.719	0.279	0.028~2.766	0.275
PT	-0.028	0.020	1.855	0.973	0.935~1.012	0.173
总胆红素	0.003	0.004	0.577	1.004	0.996~1.012	0.355
血清白蛋白	-0.038	0.019	4.149	0.963	0.928~0.999	0.042
血钠	-0.082	0.048	2.955	0.943	0.865~1.028	0.182
血糖	0.077	0.040	3.787	1.093	1.003~1.190	0.042
Child-pugh分级(B~C级vs A级)	0.320	0.455	0.494	1.127	0.482~2.635	0.783

表2 多变量Logistic回归分析肝硬化食管胃底静脉曲张破裂出血的风险因素

因素	β	SE	Wald	OR	95% CI	P
年龄(≥55岁vs <55岁)	0.089	0.303	0.087	1.076	0.597~1.941	0.807
腹水(有vs无)	1.822	0.323	31.880	6.186	3.286~11.644	<0.001
WBC计数	-0.056	0.051	1.184	0.933	0.845~1.030	0.171
PLT计数	-0.017	0.003	32.252	0.983	0.978~0.989	<0.001
血红蛋白	-0.057	0.065	0.751	0.953	0.839~1.083	0.462
INR	-1.008	1.189	0.719	0.279	0.028~2.766	0.275
PT	-0.028	0.020	1.855	0.973	0.935~1.012	0.173
总胆红素	0.003	0.004	0.577	1.004	0.996~1.012	0.355
血清白蛋白	-0.038	0.019	4.149	0.963	0.928~0.999	0.042
血钠	-0.082	0.048	2.955	0.943	0.865~1.028	0.182
血糖	0.077	0.040	3.787	1.093	1.003~1.190	0.042
Child-pugh分级(B~C级vs A级)	0.320	0.455	0.494	1.127	0.482~2.635	0.783

图1 预测肝硬化患者食管胃底静脉曲张破裂出血风险的诺模图

图2 诺模图预测肝硬化食管胃底静脉曲张破裂出血风险的ROC曲线（2A）与校正曲线（2B）

[1]	European Association for the Study of the Liver. Electronic address: easloffice@easloffice. eu, 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.
[2]	Tripathi D, Stanley AJ, Hayes PC, et al. U. K. guidelines on the management of variceal haemorrhage in cirrhotic patients[J]. Gut, 2015, 64(11): 1680-1704.
[3]	Seo YS. Prevention and management of gastroesophageal varices[J]. Clin Mol Hepatol, 2018, 24(1): 20-42.
[4]	Haq I, Tripathi D. Recent advances in the management of variceal bleeding. Gastroenterol Rep(Oxf), 2017, 5(2): 113-126.
[5]	de Franchis R, Bosch J, Garcia-Tsao G, et al. Baveno VII-Renewing consensus in portal hypertension[J]. J Hepatol, 2022, 76(4): 959-974.
[6]	Lesmana C, Raharjo M, Gani RA. Managing liver cirrhotic complications: Overview of esophageal and gastric varices[J]. Clin Mol Hepatol, 2020, 26(4): 444-460.
[7]	Garcia-Tsao G, Abraldes JG, Berzigotti A, et al. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases[J]. Hepatology, 2017, 65(1): 310-335.
[8]	中华医学会肝病学分会, 中华医学会消化病学分会, 中华医学会消化内镜学分会. 肝硬化门静脉高压食管胃静脉曲张出血的防治指南[J]. 中华内科杂志, 2016, 55(1): 57-72.
[9]	Elshaarawy O, Allam N, Abdelsameea E, et al. Platelet-albumin-bilirubin score-a predictor of outcome of acute variceal bleeding in patients with cirrhosis[J]. World J Hepatol, 2020, 12(3): 99-107.
[10]	Luo R, Gao J, Gan W, et al. Clinical-radiomics nomogram for predicting esophagogastric variceal bleeding risk noninvasively in patients with cirrhosis[J]. World J Gastroenterol, 2023, 29(6): 1076-1089.
[11]	Takehara T, Sakamori R. Remaining challenges for the noninvasive diagnosis of esophageal varices in liver cirrhosis[J]. Esophagus, 2020, 17(1): 19-24.
[12]	Hou Y, Yu H, Zhang Q, et al. Machine learning-based model for predicting the esophagogastric variceal bleeding risk in liver cirrhosis patients[J]. Diagn Pathol, 2023, 18(1): 29.
[13]	连佳, 韩涛, 向慧玲, 等. 肝硬化食管胃静脉曲张出血患者胃镜治疗术后再出血的影响因素分析[J]. 临床肝胆病杂志, 2021, 37(9): 5.
[14]	门昌君, 张国梁, 邵娴. 基于超声内镜及临床数据预测肝硬化患者出血风险的列线图模型建立[J]. 中华肝脏病杂志, 2021, 29(8): 759-765.
[15]	Zhang Q, Niu S, Yang L, et al. A novel prognostic model for predicting the risk of first variceal hemorrhage in patients with HBV-related cirrhosis[J]. Front Cell Infect Microbiol, 2023, 13: 1062172.
[16]	中华医学会肝病学分会. 肝硬化诊治指南[J]. 中华肝脏病杂志, 2019, 27(11): 20.
[17]	中华医学会外科学分会脾及门静脉高压外科学组. 肝硬化门静脉高压症食管、胃底静脉曲张破裂出血诊治专家共识(2019版)[J]. 中国实用外科杂志, 2019, 39(12): 1241-1247.
[18]	El Sheref S, Afify S, Berengy MS. Clinical characteristics and predictors of esophagogastric variceal bleeding among patients with HCV-induced liver cirrhosis: An observational comparative study[J]. PLoS One, 2022, 17(10): e0275373.
[19]	Elsebaey MA, Tawfik MA, Elshweikh SA, et al. Impact of Helicobacter pylori Infection on Gastric Variceal Bleeding among Patients with Liver Cirrhosis[J]. Gastroenterol Res Pract, 2019, 2019: 6529420.
[20]	Kleber G, Sauerbruch T, Ansari H, et al. Prediction of variceal hemorrhage in cirrhosis: a prospective follow-up study[J]. Gastroenterology, 1991, 100(5 Pt 1): 1332-1337.
[21]	Liu H, Zhang Q, Gao F, et al. Platelet Count/Spleen Thickness Ratio and the Risk of Variceal Bleeding in Cirrhosis With Esophagogastric Varices[J]. Front Med(Lausanne), 2022, 9: 870351.
[22]	Yu S, Chen W, Jiang Z. Platelet count/spleen volume ratio has a good predictive value for esophageal varices in patients with hepatitis B liver cirrhosis[J]. PLoS One, 2021, 16(12): e0260774.
[23]	Metwally K, Essam T, Atwa A, et al. Helicobacter pylori versus platelet-to-spleen ratio as a risk factor for variceal bleeding in patients with liver-cirrhosis-related portal hypertension[J]. Am J Med Sci, 2022, 364(1): 23-28.
[24]	Driver BE, Horton G, Barkun A, et al. Validation of a decision rule to predict patients at low risk of variceal upper gastrointestinal hemorrhage[J]. Am J Emerg Med, 2021, 44: 267-271.
[25]	Liu CH, Liu S, Zhao YB, et al. Development and validation of a nomogram for esophagogastric variceal bleeding in liver cirrhosis: A cohort study in 1099 cases[J]. J Dig Dis, 2022, 23(10): 597-609.

[1]	兰华, 高丽莎, 申明, 张铭光. 内镜黏膜下剥离术后溃疡出血的研究进展[J]. 中华普外科手术学杂志(电子版), 2024, 18(04): 467-469.
[2]	丁关棣, 黄云, 曹震, 刘刚. 胃癌根治术后感染性并发症预测：基于真实世界数据的Nomogram模型开发与验证[J]. 中华普外科手术学杂志(电子版), 2024, 18(03): 261-266.
[3]	张阳, 纽燕娜, 常丽蓉, 唐国华, 赵萍. ERAS理念下肝棘球蚴病术后并发症风险预测模型构建[J]. 中华普外科手术学杂志(电子版), 2024, 18(03): 287-290.
[4]	解良婕, 王剑, 阳韬. 采用AI的CT影像特征对肺结节良恶性鉴别的价值分析[J]. 中华肺部疾病杂志(电子版), 2024, 17(02): 242-246.
[5]	周文欢, 杨黎. AECOPD低钠血症发生风险及预测因素分析[J]. 中华肺部疾病杂志(电子版), 2024, 17(02): 313-315.
[6]	刘起帆, 蒋安. 肝硬化门静脉高压症门静脉压力无创测量进展[J]. 中华肝脏外科手术学电子杂志, 2024, 13(03): 270-275.
[7]	杨竞, 周光文. 肝硬化门静脉高压症治疗后再出血危险因素分析及预测模型构建[J]. 中华肝脏外科手术学电子杂志, 2024, 13(03): 296-301.
[8]	王如海, 韩超, 于强, 胡海成, 孙菲琳, 杨震. 重型创伤性脑损伤患者术后慢性意识障碍的危险因素及其预测价值[J]. 中华神经创伤外科电子杂志, 2024, 10(02): 78-83.
[9]	苗楠, 宗子钰. 脑出血后继发性脑损伤与线粒体相关机制的研究进展[J]. 中华神经创伤外科电子杂志, 2024, 10(02): 107-111.
[10]	周军, 赵志明, 刘运锋, 唐兆伟, 宋常华, 刘杰, 李浩然, 吴绍光. 神经内镜下脑室血肿清除术与脑室外引流术治疗脑室内出血的疗效分析[J]. 中华脑科疾病与康复杂志(电子版), 2024, 14(02): 86-92.
[11]	董西朝, 王林林, 袁致海, 高文文. 超早期经脑沟裂入路与经脑回皮质入路显微手术治疗基底节区脑出血的疗效分析[J]. 中华脑科疾病与康复杂志(电子版), 2024, 14(02): 100-105.
[12]	鲁悦, 李伟, 庄宗, 王娟, 赵鹏来, 杭春华. 脑出血继发吉兰-巴雷综合征二例报道并文献复习[J]. 中华脑科疾病与康复杂志(电子版), 2024, 14(02): 120-123.
[13]	杨巨顺, 何伯圣. 急性肠系膜缺血不可逆肠坏死预测因素的研究进展[J]. 中华消化病与影像杂志(电子版), 2024, 14(03): 275-281.
[14]	戚泽雪, 赵连晖, 王广川, 张春清. 从国内专家共识推荐意见更新探讨经颈静脉肝内门体分流术的临床应用进展[J]. 中华消化病与影像杂志(电子版), 2024, 14(03): 193-196.
[15]	赵倩, 刘文超, 李玺琳, 章邱东. 老年急性脑梗死诱发胃肠损伤的风险因素分析及模型构建[J]. 中华消化病与影像杂志(电子版), 2024, 14(03): 213-217.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

Construction of a normogram model for predicting the risk of esophageal and gastric varices bleeding in cirrhosis

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

Construction of a normogram model for predicting the risk of esophageal and gastric varices bleeding in cirrhosis