瘦型代谢相关脂肪性肝病患者肝纤维化程度与颈动脉斑块的相关性分析

章帅; 靳寿璐; 李晚情; 史茜菁; 梁好; 董浩; 陆戴龙; 朱滢; 向晓星; 刘军

doi:10.12449/JCH260212

瘦型代谢相关脂肪性肝病患者肝纤维化程度与颈动脉斑块的相关性分析

DOI: 10.12449/JCH260212

章帅¹,
靳寿璐¹,
李晚情¹,
史茜菁¹,
梁好²,
董浩³,
陆戴龙⁴,
朱滢¹,
向晓星¹,
刘军^1, , ,

1.
扬州大学附属苏北人民医院消化内科，江苏扬州 225001
2.
扬州大学附属苏北人民医院心血管内科，江苏扬州 225001
3.
扬州大学附属苏北人民医院肝胆外科，江苏扬州 225001
4.
扬州大学附属苏北人民医院胃肠外科，江苏扬州 225001

基金项目:

江苏省基础研究计划（自然科学基金）青年基金项目 (BK20240498);

国家自然科学基金青年项目 (82400623)

伦理学声明：本研究方案于2024年12月16日经由扬州大学附属苏北人民医院伦理审查委员会审批，批号：2024ky342，患者均签署知情同意书。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：章帅负责统计学分析，设计论文框架，起草论文；梁好负责统计学分析，绘制图表；史茜菁、靳寿璐、李晚情、董浩、陆戴龙负责数据收集及分析；朱滢、向晓星负责论文修改；刘军负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
刘军，sbyy_liujun@163.com（ORCID： 0000-0001-8738-6548）

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出版历程
- 收稿日期: 2025-09-21
- 录用日期: 2025-10-27
- 出版日期: 2026-02-25

Correlation between liver fibrosis degree and carotid plaque in patients with lean metabolic dysfunction-associated fatty liver disease

1.
Department of Gastroenterology，Subei People’s Hospital Affiliated to Yangzhou University，Yangzhou，Jiangsu 225001，China
2.
Department of Cardiology，Subei People’s Hospital Affiliated to Yangzhou University，Yangzhou，Jiangsu 225001，China
3.
Department of Hepatobiliary，Subei People’s Hospital Affiliated to Yangzhou University，Yangzhou，Jiangsu 225001，China
4.
Department of Gastrointestinal Surgery，Subei People’s Hospital Affiliated to Yangzhou University，Yangzhou，Jiangsu 225001，China

Research funding:

Jiangsu Provincial Basic Research Program （Natural Science Foundation） Youth Fund Project (BK20240498);

National Natural Science Foundation of China Youth Project (82400623)

More Information

Corresponding author: LIU Jun， sbyy_liujun@163.com （ORCID： 0000-0001-8738-6548）

摘要

摘要: 目的通过观察瘦型代谢相关脂肪性肝病（MAFLD）患者的无创肝纤维化指标，分析其与颈动脉斑块（CP）的关系，为筛查相关高危人群提供依据。方法以苏北人民医院2021年1月—2023年6月体检的957例瘦型MAFLD患者为观察队列，以是否患有CP为结局，选择肝纤维化-4（FIB-4）指数、非酒精性脂肪肝病纤维化评分（NFS）作为肝纤维化程度评价指标。对于符合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。多元Logistic回归、限制性立方样条分析、受试者操作特征曲线和中介效应分析被用于探究肝纤维化程度与CP患病的关系。结果瘦型MAFLD人群中CP患病率为36.6%。CP组（n=350）的男性、吸烟、糖尿病、高血压比例，以及年龄、血肌酐、血尿素氮、甘油三酯、空腹血糖、天冬氨酸氨基转移酶、天冬氨酸氨基转移酶/丙氨酸氨基转移酶、NFS、FIB-4指数均高于非CP组（n=607），而血小板计数、白蛋白水平则低于非CP组（P值均<0.05）。多元Logistic回归显示，在完全校正混杂因素后，FIB-4指数（OR=2.979， 95%CI：2.141～4.219）和NFS（OR=1.747， 95%CI：1.499～2.046）均与CP患病呈正相关（P值均<0.001）。FIB-4指数和NFS均对CP有较好的预测价值。高血压通过影响肝纤维化指标对CP的患病率有显著的间接效应，经NFS和FIB-4指数评估，中介效应分别为40.8%和39.5%（P值均<0.001）。结论在瘦型MAFLD患者中，NFS和FIB-4指数与CP的患病率呈显著正相关。肝纤维化指标可能在高血压与CP的关联中起中介作用。针对高血压和肝纤维化指标的干预措施可能有助于预防和减缓CP进程。
- 代谢相关脂肪性肝病 /
- 颈动脉斑块 /
- 肝纤维化
Abstract: Objective To investigate the association between noninvasive liver fibrosis markers and carotid plaque （CP） in patients with lean metabolic dysfunction-associated fatty liver disease （MAFLD）， and to provide a basis for screening high-risk populations. Methods A total of 957 patients with lean MAFLD who underwent physical examination in Subei People’s Hospital from January 2021 to June 2023 was enrolled as the observation cohort， with the presence or absence of CP as the outcome， and fibrosis-4 （FIB-4） index and nonalcoholic fatty liver disease fibrosis score （NFS） were used to assess liver fibrosis degree. 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. The multivariate logistic regression analysis， the restricted cubic spline analysis， the receiver operating characteristic curve， and the mediation effect analysis were used to investigate the association between liver fibrosis degree and CP. Results The prevalence rate of CP was 36.6% in the lean MAFLD population. Compared with the non-CP group（n=607）， the CP group （n=350） had a significantly higher proportion of male patients， a significantly higher proportion of patients with smoking/diabetes/hypertension， and significantly higher levels of age， creatinine， blood urea nitrogen， triglycerides， fasting blood glucose， aspartate aminotransferase， aspartate aminotransferase/alanine aminotransferase ratio， NFS， and FIB-4 index， as well as significantly lower levels of platelet count and albumin （all P<0.05）. The multivariate logistic regression analysis showed that after adjustment for confounding factors， FIB-4 index （odds ratio［OR］=2.979， 95% confidence interval［CI］：2.141 — 4.219， P<0.001） and NFS （OR=1.747， 95%CI： 1.499 — 2.046， P<0.001） were positively correlated with CP. Both FIB-4 index and NFS had a good value in predicting CP. Hypertension had a significant indirect effect on the prevalence rate of CP through its impact on liver fibrosis markers， and its mediating effect accounted for 39.5% — 40.8% of the total effect （P<0.001）. Conclusion In patients with lean MAFLD， NFS and FIB-4 index are significantly positively correlated with the prevalence rate of CP， and they can be used as potential epidemiological predictive indicators. Liver fibrosis markers may play a mediating role in the association between hypertension and CP. Interventions targeting hypertension and liver fibrosis markers may help to prevent and delay the progression of CP.
- Metabolic Dysfunction-Associated Fatty Liver Disease /
- Carotid Plaque /
- Liver Fibrosis

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注： FIB-4指数，纤维化-4指数；NFS，非酒精性脂肪性肝病纤维化评分；OR，比值比；CI，置信区间。

图 1 FIB-4指数和NFS与颈动脉斑块患病的限制性立方样条曲线

Figure 1. Restricted cubic spline curves of FIB-4 Index and NFS

下载: 全尺寸图片幻灯片

注： NFS，非酒精性脂肪性肝病纤维化评分；AUC，受试者操作特征曲线下面积；FIB-4指数，肝纤维化-4指数；CI，置信区间。

图 2 肝纤维化指标预测颈动脉斑块的受试者操作特征曲线

Figure 2. Receiver operating characteristic curves for predicting carotid plaque prevalence using liver fibrosis indicators

下载: 全尺寸图片幻灯片

注： FIB-4指数，纤维化-4指数；NFS，非酒精性脂肪性肝病纤维化评分；CP，颈动脉斑块；CI，置信区间。

图 3 FIB-4指数和NFS的中介效应分析

Figure 3. Mediation effect analysis of FIB-4 and NFS

下载: 全尺寸图片幻灯片

表 1 一般资料比较

Table 1. Comparison of general information

变量	CP组（n=350）	非CP组（n=607）	统计值	P值
性别［例（%）］			χ²=5.652	0.017
男	247（70.6）	381（62.8）
女	103（29.4）	226（37.2）
年龄（岁）	54.29±11.89	42.96±11.15	t=14.528	<0.001
BMI（kg/m²）	22.74±0.98	22.65±1.10	t=1.291	0.197
吸烟［例（%）］	97（27.7）	110（18.1）	χ²=11.491	0.001
腹型肥胖［例（%）］	30（8.6）	48（7.9）	χ²=0.057	0.811
糖尿病［例（%）］	74（21.1）	36（5.9）	χ²=49.013	<0.001
高血压［例（%）］	142（40.6）	125（20.6）	χ²=43.061	<0.001
SUA（μmol/L）	369.73±77.20	369.09±78.26	t=1.466	0.143
PLT（×10⁹/L）	228.53±56.62	241.39±56.01	t=-3.401	0.001
Alb（g/L）	44.84±2.22	45.33±2.43	t=-3.119	0.002
SCr（μmol/L）	66.86±14.17	64.87±14.12	t=2.092	0.037
BUN（mmol/L）	5.49±1.38	5.11±1.25	t=4.172	<0.001
TG（mmol/L）	1.86（1.34～2.66）	1.67（1.28～2.37）	Z=3.014	0.003
FPG（mmol/L）	5.67±1.46	5.23±1.28	t=4.678	<0.001
LDL-C（mmol/L）	2.88±0.80	2.87±0.68	t=0.111	0.911
HDL-C（mmol/L）	1.150±0.249	1.160±0.234	t=-0.871	0.384
TBil（μmol/L）	13.76±5.19	13.81±5.57	t=-0.134	0.893
AST（U/L）	19（16～23）	18（15～23）	Z=1.739	0.039
ALT（U/L）	21（16～29）	21（15～32）	Z=0.112	0.967
AST/ALT	0.91（0.73～1.13）	0.87（0.67～1.08）	Z=2.071	0.039
NFS	-2.23（-3.12～-1.52）	-3.21（-3.83～-2.43）	Z=10.435	<0.001
FIB-4指数	1.04（0.73～1.35）	0.71（0.50～0.96）	Z=8.535	<0.001
注：CP，颈动脉斑块；BMI，体重指数；SUA，血清尿酸；PLT，血小板；Alb，白蛋白；SCr，血清肌酐；TG，甘油三酯；FPG，空腹葡萄糖；LDL-C，低密度脂蛋白胆固醇；HDL-C，高密度脂蛋白胆固醇；TBil，总胆红素；AST，天冬氨酸氨基转移酶；ALT，丙氨酸氨基转移酶；NFS，非酒精性脂肪性肝病纤维化评分；FIB-4指数，纤维化-4指数。

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表 2 多元Logistic回归分析

Table 2. Multivariate Logistic regression analysis

变量	原始队列		倾向性评分匹配后的队列
变量	模型1	模型2	模型1	模型2
NFS
OR	1.917	1.747	1.366	1.295
95%CI	1.659～2.227	1.499～2.046	1.199～1.561	1.124～1.488
P值	<0.001	<0.001	<0.001	<0.001
FIB-4指数
OR	3.552	2.979	1.736	1.489
95%CI	2.650～4.836	2.141～4.219	1.312～2.342	1.224～1.895
P值	<0.001	<0.001	<0.001	<0.001
注：FIB-4指数，纤维化-4指数；NFS，非酒精性脂肪性肝病纤维化评分；OR，比值比；CI，置信区间。

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