非酒精性脂肪性肝病发生进展期肝纤维化的危险因素及列线图预测模型构建

杨金秋; 赵文霞; 周铖; 刘通

doi:10.12449/JCH240812

非酒精性脂肪性肝病发生进展期肝纤维化的危险因素及列线图预测模型构建

DOI: 10.12449/JCH240812

杨金秋¹,
赵文霞^2, , ,,
周铖¹,
刘通¹

1.
河南中医药大学第一临床医学院，郑州 450000
2.
河南中医药大学第一附属医院脾胃肝胆科，郑州 450000

基金项目:

河南省中医药科学研究专项课题项目 (2018JDZX005);

河南省中医药科学研究专项课题项目 (2022JDZX006);

“双一流”创建工程中医学学科项目任务书 (HSRP-DFCTCM-2023-8-16);

河南省特色骨干学科中医学学科建设项目 (STG-ZYXKY-2020024);

全国名中医传承工作室建设项目 (Guozhongyiyao Renjiaohan ［2022］ No.245)

伦理学声明：本研究方案于2023年11月17日经由河南中医药大学第一附属医院伦理委员会审批，批号：2023HL-441。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：杨金秋负责课题设计，资料分析，撰写论文；周铖、刘通参与收集数据，修改论文；赵文霞负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
赵文霞， zhao-wenxia@163.com （ORCID： 0000-0001-6666-9469）

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出版历程
- 收稿日期: 2023-11-22
- 录用日期: 2023-12-11
- 出版日期: 2024-08-25

Risk factors for the development of advanced liver fibrosis in nonalcoholic fatty liver disease and establishment of a nomogram model

1.
The First Clinical Medical College of Henan University of Chinese Medicine，Zhengzhou 450000，China
2.
Spleen，Stomach and Hepatobiliary Department，The First Affiliated Hospital of Henan University of Chinese Medicine，Zhengzhou 450000，China

Research funding:

Traditional Chinese Medicine Science Research Project of Henan Province (2018JDZX005);

Traditional Chinese Medicine Science Research Project of Henan Province (2022JDZX006);

“Double First Class” Creation of Engineering Traditional Chinese Medicine Discipline Project Task Book (HSRP-DFCTCM-2023-8-16);

Subject Construction Project of Traditional Chinese Medicine in Henan Province (STG-ZYXKY-2020024);

National Famous TCM Doctor Studio Construction (Guozhongyiyao Renjiaohan ［2022］ No.245)

More Information

Corresponding author: ZHAO Wenxia， zhao-wenxia@163.com （ORCID： 0000-0001-6666-9469）

摘要

摘要: 目的通过分析非酒精性脂肪性肝病（NAFLD）进展期肝纤维化患者的临床特征，探讨进展期肝纤维化发生的危险因素，并建立预测进展期肝纤维化发生风险的列线图。方法回顾性分析2022年1月—2023年10月就诊于河南中医药大学第一附属医院的406例NAFLD患者的临床资料，依据FibroScan检测的肝脏弹性值（LSM）是否≥11.0 kPa，分为进展期肝纤维化组（65例）和非进展期纤维化组（341例），收集患者一般资料、实验室检查指标、既往病史。正态分布的计量资料两组间比较采用成组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χ²检验。通过多因素Logistic回归分析筛选独立危险因素，并基于此建立列线图，采用受试者工作特征曲线（ROC曲线）评估该列线图模型的区分度，校准曲线评价其有效性。结果单因素分析显示，进展期肝纤维化组患者的年龄、受控衰减参数、总胆红素、直接胆红素、间接胆红素、球蛋白、丙氨酸氨基转移酶、门冬氨酸氨基转移酶、碱性磷酸酶、谷氨酰转移酶、葡萄糖、体质量指数、糖尿病史与非进展期肝纤维化组比较，差异均有统计学意义（P值均<0.05）。进一步通过Logistic回归分析发现受控衰减参数（OR=1.015，95%CI：1.006～1.024，P=0.010）、直接胆红素（OR=1.345，95%CI：1.139～1.590，P=0.001）、碱性磷酸酶（OR=1.019，95%CI：1.008～1.029，P=0.001）、谷氨酰转移酶（OR=1.004，95%CI：1.000～1.008，P=0.035）和身体质量指数（OR=1.240，95%CI：1.137～1.353，P=0.001）是NAFLD进展期肝纤维化发生的独立危险因素。基于多因素回归结果构建列线图，ROC曲线分析结果显示该列线图模型预测NAFLD人群发生进展期肝纤维化的曲线下面积为0.841（95%CI：0.791～0.891）；校准曲线显示进展期肝纤维化发生的观测值与预测值拟合度较好。结论受控衰减参数、身体质量指数、直接胆红素、碱性磷酸酶及谷氨酰转移酶水平升高是NAFLD进展期肝纤维化的独立影响因素，基于此建立的列线图预测效能良好，对进展期肝纤维化具有一定的预测价值。
- 非酒精性脂肪性肝病 /
- 肝纤维化 /
- 危险因素 /
- 列线图
Abstract: Objective To investigate the risk factors for the development of advanced liver fibrosis by analyzing the clinical features of patients with in nonalcoholic fatty liver disease （NAFLD） and advanced liver fibrosis， and to establish a nomogram model for predicting the risk of advanced liver fibrosis. Methods A retrospective analysis was performed for the clinical data of 406 NAFLD patients who attended The First Affiliated Hospital of Henan University of Chinese Medicine from January 2022 to October 2023， and according to whether liver stiffness measurement （LSM） measured by FibroScan was ≥11.0 kPa， the patients were divided into advanced liver fibrosis group with 65 patients and non-advanced liver fibrosis group with 341 patients. Related data were collected， including general information， laboratory markers， and medical history. The independent-samples 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 multivariate Logistic regression analysis was used to identify independent risk factors， and a nomogram model was established based on these factors. The receiver operating characteristic （ROC） curve was used to evaluate the discriminatory ability of the nomogram model， and the calibration curve was used to evaluate its effectiveness. Results The univariate analysis showed that there were significant differences between the advanced liver fibrosis group and the non-advanced liver fibrosis group in age， controlled attenuation parameter （CAP）， total bilirubin， direct bilirubin （DBil）， indirect bilirubin， globin， alanine aminotransferase， aspartate aminotransferase， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， glucose， body mass index （BMI）， and history of diabetes （all P<0.05）. The multivariate Logistic regression analysis showed that CAP （odds ratio ［OR］=1.015， 95% confidence interval ［CI］： 1.006‍ ‍—‍ ‍1.024， P=0.010）， DBil （OR=1.345， 95%CI： 1.139‍ ‍—‍ ‍1.590， P=0.001）， ALP （OR=1.019， 95%CI： 1.008‍ ‍—‍ ‍1.029， P=0.001）， GGT （OR=1.004， 95%CI： 1.000‍ ‍—‍ ‍1.008， P=0.035） and BMI （OR=1.240， 95%CI： 1.137‍ ‍—‍ ‍1.353， P=0.001） were independent risk factors for the development of advanced liver fibrosis in NAFLD. A nomogram model was established based on the results of the multivariate Logistic regression analysis. The ROC curve analysis showed that this nomogram model had an area under the ROC curve of 0.841 （95%CI： 0.791‍ ‍—‍ ‍0.891） in predicting the development of advanced liver fibrosis in the NAFLD population， and the calibration curve showed a good degree of fitting between the observed and predicted values for the development of advanced liver fibrosis. Conclusion Elevated levels of CAP， BMI， DBil， ALP， and GGT are independent risk factors for advanced liver fibrosis in NAFLD. The nomogram model established based on these factors has good predictive performance and a certain value in predicting advanced liver fibrosis.
- Non-Alcoholic Fatty Liver Disease /
- Hepatic Fibrosis /
- Risk Factors /
- Nomograms

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图 1 预测NAFLD患者发生进展期肝纤维化的列线图

Figure 1. Nomogram for predicting the occurrence of advanced liver fibrosis in NAFLD patients

下载: 全尺寸图片幻灯片

图 2 列线图模型预测NAFLD人群发生进展期肝纤维化的ROC曲线

Figure 2. The ROC curve of predicting advanced liver fibrosis in NAFLD population using Nomogram

下载: 全尺寸图片幻灯片

图 3 模型校准曲线

Figure 3. Model calibration graphics

下载: 全尺寸图片幻灯片

表 1 两组间一般资料比较

Table 1. Comparison of general data between two groups

指标	进展期肝纤维化组（n=65）	非进展期肝纤维化组（n=341）	统计值	P值
性别［例（%）］			χ²=0.014	0.906
男	50（76.9）	260（76.2）
女	15（23.1）	81（23.8）
年龄（岁）	39.09±11.96	39.25±12.25	t=1.985	0.048
CAP（dB/m）	341（314～341）	306（272～334）	Z=-4.999	0.001
TBil（μmol/L）	18.4（13.7～23.3）	14.2（10.9～18.6）	Z=-3.857	0.001
DBil（μmol/L）	3.9（2.9～5.3）	2.8（2.0～4.0）	Z=-4.734	0.001
IBil（μmol/L）	14.3（10.3～18.0）	11.2（8.8～14.7）	Z=-3.302	0.001
Alb（g/L）	44.7（42.4～46.5）	44.4（41.9～46.9）	Z=-0.438	0.661
Glb（g/L）	28.4（26.3～31.4）	27.2（25.0～29.5）	Z=-2.348	0.019
ALT（U/L）	61.4（38.3～112.9）	39.4（23.6～67.2）	Z=-4.238	0.001
AST（U/L）	42.2（30.7～65.3）	27.4（21.1～38.4）	Z=-6.212	0.001
ALP（U/L）	86.3（72.9～106.1）	76.8（66.0～91.4）	Z=-3.481	0.001
GGT（U/L）	59.5（43.3～105.1）	44.1（28.8～80.2）	Z=-3.735	0.001
Cr（μmol/L）	61.5（49.9～74.8）	65.2（56.4～72.7）	Z=-0.736	0.465
UA（μmol/L）	403.95（322.10～504.05）	395.80（334.50～473.90）	Z=-0.627	0.530
GLU（μmol/L）	5.77（4.98～6.64）	5.28（4.85～5.80）	Z=-2.852	0.040
TC（mmol/L）	5.14（4.59～5.70）	4.83（4.17～5.51）	Z=-1.611	0.107
TG（mmol/L）	1.93（1.41～2.59）	1.86（1.31～2.78）	Z=-0.008	0.994
HDL-C（mmol/L）	1.03（0.90～1.30）	1.11（0.95～1.29）	Z=-0.905	0.366
BMI（kg/m²）	31.4（28.5～34.6）	28.1（25.4～30.7）	Z=-6.061	0.001
糖尿病病史［例（%）］	15（23.1）	42（12.3）	χ²=5.238	0.022
高血压病史［例（%）］	12（18.5）	64（18.8）	χ²=0.003	0.954
结直肠息肉病史［例（%）］	11（16.9）	95（27.9）	χ²=3.655	0.056

下载: 导出CSV

表 2 NAFLD患者发生进展期肝纤维化的危险因素

Table 2. Risk factors for advanced liver fibrosis in NAFLD patients

变量	B值	Wald	OR	95%CI	P值
CAP	0.015	3.31	1.015	1.006～1.024	0.010
DBil	0.297	3.48	1.345	1.139～1.590	0.001
ALP	0.019	3.52	1.019	1.008～1.029	0.001
GGT	0.004	2.10	1.004	1.000～1.008	0.035
BMI	0.215	4.84	1.240	1.137～1.353	0.001

下载: 导出CSV

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