
浏览全部资源
扫码关注微信
重庆医科大学附属第二医院健康医学中心,重庆 404100
梅 佳,Email:2023122182@stu.cqmu.edu.cn ,研究方向:慢病管理、代谢相关脂肪肝病。
陈 英,Email:300492@hospital.cqmu.edu.cn。
收稿:2025-04-29,
修回:2025-07-24,
纸质出版:2026-01-28
移动端阅览
梅佳,王丽华,谢云彩等.炎症在代谢功能障碍相关脂肪性肝病肝纤维化与亚临床动脉粥样硬化间的中介效应分析[J].重庆医科大学学报,2026,51(01):130-138.
Mei Jia,Wang Lihua,Xie Yuncai,et al.Inflammation as a mediator between fibrosis in metabolic dysfunction-associated steatotic liver disease and subclinical atherosclerosis[J].Journal of Chongqing Medical University,2026,51(01):130-138.
梅佳,王丽华,谢云彩等.炎症在代谢功能障碍相关脂肪性肝病肝纤维化与亚临床动脉粥样硬化间的中介效应分析[J].重庆医科大学学报,2026,51(01):130-138. DOI: 10.13406/j.cnki.cyxb.003950.
Mei Jia,Wang Lihua,Xie Yuncai,et al.Inflammation as a mediator between fibrosis in metabolic dysfunction-associated steatotic liver disease and subclinical atherosclerosis[J].Journal of Chongqing Medical University,2026,51(01):130-138. DOI: 10.13406/j.cnki.cyxb.003950.
目的
2
分析炎症、代谢功能障碍相关脂肪性肝病(metabolic dysfunction-associated steatotic liver disease MASLD)与亚临床动脉粥样硬化(subclinical atherosclerosis SCA)患者的关系,探讨炎症在肝纤维化对SCA影响中的作用。
方法
2
连续纳入重医附二院江南院区体检中心2023年10月31日至2024年11月1日符合纳排标准的9 791例患者,从电子病历收集患者信息。
结果
2
在控制传统心血管风险因素后,多因素logistic结果显示,患MASLD与PLR(1.00,
P
=0.01)和MHR(1.21,
P
<
0.001)存在显著相关;SCA的发生与APRI(1.43,
P
=0.036)、LMR(0.96,
P
=0.019)和SIRI(0.71,
P
=0.018)存在显著相关;中介分析结果显示,FIB-4与APRI分别通过炎症因子MHR(95%CI=0.005~0.032)、SII(95%CI=-0.068~-0.032)、SIRI(95%CI=-0.011~-0.003)和NLR(95%CI=-0.02~-0.002)、PLR(95%CI=0.055~0175)、LMR(95%CI=0.011~0.001)、SIRI(95%CI=-0.042~-0.002)
对SCA的发生发挥部分中介的作用。
结论
2
MASLD肝纤维化对SCA的发生具有直接效应,同时还通过炎症因子对其产生影响,强调了MASLD患者在早期筛查CVD疾病风险的重要性,同时抗炎疗法可能会在MASLD的未来管理中发挥重要作用。
Objective
2
To analyze the relationships of inflammation,metabolic dysfunction-associated steatotic liver disease (MASLD),and subclinical atherosclerosis(SCA),and to explore the role of inflammation in the impact of liver fibrosis on SCA.
Methods
2
A total of 9791 patients who met the inclusion and exclusion criteria were consecutively enrolled from the Health Examination Center at the Jiangnan Campus of The Second Affiliated Hospital of Chongqing Medical University between October 31,2023 and November 1,2024. Patient information was collected from electronic medical records.
Results
2
After adjusting for traditional cardiovascular risk factors,multivariate logistic regression analysis showed significant associations of MASLD with platelet-to-lymphocyte ratio (1.00,
P
=0.01) and monocyte-to-high-density lipoprotein cholesterol ratio(1.21,
P
<
0.001). The occurrence of SCA was significantly related to aspartate aminotransferase-to-platelet ratio index(1.43,
P
=0.036),lymphocyte-to-monocyte ratio(0.96,
P
=0.019),and systemic inflammation response index(0.71,
P
=0.018). Mediation analysis indicated that fibrosis-4 index exerted partial mediating effects on the occurrence of SCA through inflammatory markers monocyte-to-high-density lipoprotein cholesterol ratio(95%CI=0.005 to 0.032),systemic immune-inflammation index (95%CI: -0.068 to -0.032),and systemic inflammation response index(95%CI= -0.011 to -0.003),while aspartate aminotransferase-to-platelet ratio index through neutrophil-to-lymphocyte ratio(95%CI=-0.02 to -0.002),platelet-to-lymphocyte ratio(95%CI=0.055 to 0.175),lymphocyte-to-monocyte ratio(95%CI=0.011 to 0.001),and systemic inflamma
tion response index(95%CI=-0.042 to -0.002).
Conclusion
2
Liver fibrosis in MASLD has a direct effect on the occurrence of SCA and also influences it through inflammatory markers. These findings highlight the importance of early screening for cardiovascular disease risk in MASLD patients and suggest that anti-inflammatory therapy may play a significant role in the future management of MASLD.
Younossi ZM , Golabi P , Paik JM , et al . The global epidemiology of nonalcoholic fatty liver disease(NAFLD) and nonalcoholic steatohepatitis(NASH):a systematic review [J ] . Hepatology , 2023 , 77 ( 4 ): 1335 - 1347 .
Eslam M , Newsome PN , Sarin SK , et al . A new definition for metabolic dysfunction-associated fatty liver disease:an international expert consensus statement [J ] . J Hepatol , 2020 , 73 ( 1 ): 202 - 209 .
Nan Y , An J , Bao J , et al . The Chinese Society of Hepatology position statement on the redefinition of fatty liver disease [J ] . J Hepatol , 2021 , 75 ( 2 ): 454 - 461 .
Rinella ME , Lazarus JV , Ratziu V , et al . A multisociety Delphi consensus statement on new fatty liver disease nomenclature [J ] . Ann Hepatol , 2024 , 29 ( 1 ): 101133 .
Hagström H , Vessby J , Ekstedt M , et al . 99% of patients with NAFLD meet MASLD criteria and natural history is therefore identical [J ] . J Hepatol , 2024 , 80 ( 2 ): 76 - 77 .
Yang A , Zhu X , Zhang L , et al . Transitioning from NAFLD to MAFLD and MASLD:consistent prevalence and risk factors in a Chinese cohort [J ] . J Hepatol , 2024 , 80 ( 4 ): 154 - 155 .
Adams LA , Anstee QM , Tilg H , et al . Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases [J ] . Gut , 2017 , 66 ( 6 ): 1138 - 1153 .
Chun HS , Lee M , Lee JS , et al . Metabolic dysfunction associated fatty liver disease identifies subjects with cardiovascular risk better than non-alcoholic fatty liver disease [J ] . Liver Int , 2023 , 43 ( 3 ): 608 - 625 .
Targher G , Byrne CD , Tilg H . MASLD:a systemic metabolic disorder with cardiovascular and malignant complications [J ] . Gut , 2024 , 73 ( 4 ): 691 - 702 .
Zheng HX , Sechi LA , Navarese EP , et al . Metabolic dysfunction-associated steatotic liver disease and cardiovascular risk:a comprehensive review [J ] . Cardiovasc Diabetol , 2024 , 23 ( 1 ): 346 .
Lee HH , Lee HA , Kim EJ , et al . Metabolic dysfunction-associated steatotic liver disease and risk of cardiovascular disease [J ] . Gut , 2024 , 73 ( 3 ): 533 - 540 .
Kaya E , Yilmaz Y . Metabolic-associated fatty liver disease (MAFLD):a multi-systemic disease beyond the liver [J ] . J Clin Transl Hepatol , 2022 , 10 ( 2 ): 329 - 338 .
Zhao J , Liu L , Cao YY , et al . MAFLD as part of systemic metabolic dysregulation [J ] . Hepatol Int , 2024 , 18 ( Suppl 2 ): S834 - S847 .
Jain S , Khera R , Corrales-Medina VF , et al . “ Inflammation and arterial stiffness in humans ”[J ] . Atherosclerosis , 2014 , 237 ( 2 ): 381 - 390 .
Tacke F , Puengel T , Loomba R , et al . An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH [J ] . J Hepatol , 2023 , 79 ( 2 ): 552 - 566 .
European Association for the Study of the Liver(EASL) , European Association for the Study of Diabetes(EASD) , European Association for the Study of Obesity(EASO) . EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease(MASLD) [J ] . J Hepatol , 2024 , 81 ( 3 ): 492 - 542 .
倪平 , 陈京立 , 刘娜 . 护理研究中量性研究的样本量估计 [J ] . 中华护理杂志 , 2010 , 45 ( 4 ): 378 - 380 .
Ni P , Chen JL , Liu N . Sample size estimation for quantitative research in nursing studies [J ] . Chinese Journal of Nursing , 2010 , 45 ( 4 ): 378 - 380 .
Zhao Y , Xia J , He H , et al . Diagnostic performance of novel inflammatory biomarkers based on ratios of laboratory indicators for nonalcoholic fatty liver disease [J ] . Front Endocrinol(Lausanne) , 2022 , 13 : 981196 .
Xie RJ , Xiao MD , Li LH , et al . Association between SII and hepatic steatosis and liver fibrosis:a population-based study [J ] . Front Immunol , 2022 , 13 : 925690 .
Cusi K , Isaacs S , Barb D , et al . American association of clinical endocrinology clinical practice guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings:co-sponsored by the American association for the study of liver diseases(AASLD) [J ] . Endocr Pract , 2022 , 28 ( 5 ): 528 - 562 .
Lee J , Vali Y , Boursier J , et al . Prognostic accuracy of FIB-4,NAFLD fibrosis score and APRI for NAFLD-related events:a systematic review [J ] . Liver Int , 2021 , 41 ( 2 ): 261 - 270 .
National Workshop on Fatty Liver and Alcoholic Liver Disease , Chinese Society of Hepatology , Chinese Medical Association , et al . Guidelines of prevention and treatment for nonalcoholic fatty liver disease:a 2018 update [J ] . Zhonghua Gan Zang Bing Za Zhi , 2018 , 26 ( 3 ): 195 - 203 .
Stein JH , Korcarz CE , Hurst RT , et al . Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk:a consensus statement from the American society of echocardiography carotid intima-media thickness task force endorsed by the society for vascular medicine [J ] . J Am Soc Echocardiogr , 2008 , 21 ( 2 ): 93 - 111 .
Touboul PJ , Hennerici MG , Meairs S , et al . Mannheim carotid intima-media thickness and plaque consensus(2004-2006-2011) [J ] . Cerebrovasc Dis , 2012 , 34 ( 4 ): 290 - 296 .
Hayes AF , Preacher KJ . Statistical mediation analysis with a multicategorical independent variable [J ] . Br J Math Stat Psychol , 2014 , 67 ( 3 ): 451 - 470 .
温忠麟 , 叶宝娟 . 中介效应分析:方法和模型发展 [J ] . 心理科学进展 , 2014 , 22 ( 5 ): 731 - 745 .
Wen ZL , Ye BJ . Analyses of mediating effects:The development of methods and models [J ] . Adv Psychol Sci , 2014 , 22 ( 5 ): 731 - 745 .
Wang Y , Yuan T , Deng S , et al . Metabolic health phenotype better predicts subclinical atherosclerosis than body mass index-based obesity phenotype in the non-alcoholic fatty liver disease population [J ] . Front Nutr , 2023 , 10 : 1104859 .
Niederseer D , Wernly B , Aigner E , et al . NAFLD and cardiovascular diseases:epidemiological,mechanistic and therapeutic considerations [J ] . J Clin Med , 2021 , 10 ( 3 ): 467 .
Duong M , Uno K , Nankivell V , et al . Induction of obesity impairs reverse cholesterol transport in ob/ob mice [J ] . PLoS One , 2018 , 13 ( 9 ): e0202102 .
Finney AC , Das S , Kumar D , et al . The interplay between nonalcoholic fatty liver disease and atherosclerotic cardiovascular disease [J ] . Front Cardiovasc Med , 2023 , 10 : 1116861 .
孔令银 . 分析脂肪肝患者行血脂检验与血常规检验的临床诊断价值 [J ] . 中国实用医药 , 2024 , 19 ( 3 ): 75 - 78 .
Kong LY . Analysis of the Clinical Diagnostic Value of Blood Lipid and Routine Blood Tests in Patients with Fatty Liver . Chin Pract Med. , 2024 , 19 ( 3 ), 75 - 78 .
陈 娟 , 刘志龙 , 张 倩 , 等 . 超声衰减技术对肝脂肪变性定量评估的研究进展 [J ] . 中华超声影像学杂志 , 2024 , 33 ( 6 ): 548 - 552 .
Chen J , Liu ZL , Zhang Q , et al . Advances in the quantitative evaluation of hepatic steatosis by ultrasonic attenuation techniques [J ] . Chin J Ultrasonogr , 2024 , 33 ( 6 ): 548 - 552 .
Uslu AU , Sekin Y , Tarhan G , et al . Evaluation of monocyte to high-density lipoprotein cholesterol ratio in the presence and severity of metabolic syndrome [J ] . Clin Appl Thromb Hemost , 2018 , 24 ( 5 ): 828 - 833 .
Hume DA , Irvine KM , Pridans C . The mononuclear phagocyte system:the relationship between monocytes and macrophages [J ] . Trends Immunol , 2019 , 40 ( 2 ): 98 - 112 .
Zhang B , Zhang Y , Xiong L , et al . CD127 imprints functional heterogeneity to diversify monocyte responses in inflammatory diseases [J ] . J Exp Med , 2022 , 219 ( 2 ): e20211191 .
Mukherjee R , Kanti Barman P , Kumar Thatoi P , et al . Non-Classical monocytes display inflammatory features:Validation in Sepsis and Systemic Lupus Erythematous [J ] . Sci Rep , 2015 , 5 : 13886 .
Suzuki M , Pritchard DK , Becker L , et al . High-density lipoprotein suppresses the type I interferon response,a family of potent antiviral immunoregulators,in macrophages challenged with lipopolysaccharide [J ] . Circulation , 2010 , 122 ( 19 ): 1919 - 1927 .
Karatas A , Turkmen E , Erdem E , et al . Monocyte to high-density lipoprotein cholesterol ratio in patients with diabetes mellitus and diabetic nephropathy [J ] . Biomark Med , 2018 , 12 ( 9 ): 953 - 959 .
Sanyal AJ . Past,present and future perspectives in nonalcoholic fatty liver disease [J ] . Nat Rev Gastroenterol Hepatol , 2019 , 16 ( 6 ): 377 - 386 .
Xin Z , Zhu Y , Wang S , et al . Associations of subclinical atherosclerosis with nonalcoholic fatty liver disease and fibrosis assessed by non-invasive score [J ] . Liver Int , 2020 , 40 ( 4 ): 806 - 814 .
Liu X , Zhang HJ , Fang CC , et al . Association between noninvasive liver fibrosis scores and heart failure in a general population [J ] . J Am Heart Assoc , 2024 , 13 ( 22 ): e035371 .
Ishiba Y , Sumida Y , Tanaka S , et al . Japan Study Group of Non-Alcoholic Fatty Liver Disease(JSG-NAFLD). Type Ⅳ collagen 7S is the most accurate test for identifying advanced fibrosis in non-alcoholic fatty liver disease with type 2 diabetes [J ] . Hepatol Commun , 2020 , 4 ( 8 ): 1135 - 1147 .
Sin ZQ , Wu Q , Chen SH , et al . The associations of two novel inflammation indexes,SII and SIRI with the risks for cardiovascular diseases and all-cause mortality:a ten-year follow-up study in 85,154 individuals [J ] . J Inflamm Res , 2021 , 14 : 131 - 140 .
Liu Z , Zheng L . Associations between SII,SIRI,and cardiovascular disease in obese individuals:a nationwide cross-sectional analysis [J ] . Front Cardiovasc Med , 2024 , 11 : 1361088 .
Dulai PS , Singh S , Patel J , et al . Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease:Systematic review and meta-analysis [J ] . Hepatology , 2017 , 65 ( 5 ): 1557 - 1565 .
Huang Z , Shen S , Li W , et al . Macrophage WEE1 directly binds to and phosphorylates NF-κB p65 subunit to induce inflammatory response and drive atherosclerosis [J ] . Adv Sci(Weinh) , 2025 : e2503192 .
Qiu X , Shen S , Jiang NZ , et al . Associations between systemic inflammatory biomarkers and metabolic dysfunction associated steatotic liver disease:a cross-sectional study of NHANES 2017-2020 [J ] . BMC Gastroenterol , 2025 , 25 ( 1 ): 42 .
Libby P , Ridker PM , Hansson GK . Progress and challenges in translating the biology of atherosclerosis [J ] . Nature , 2011 , 473 ( 7347 ): 317 - 325 .
Anstee QM , Mantovani A , Tilg H , et al . Risk of cardiomyopathy and cardiac arrhythmias in patients with nonalcoholic fatty liver disease [J ] . Nat Rev Gastroenterol Hepatol , 2018 , 15 ( 7 ): 425 - 439 .
Purón-González E , González-Cantú A , Coronado-Alejandro EU , et al . Predictive markers of nonalcoholic fatty liver disease in lean patients. A multinomial regression model and a 2k factorial analysis [J ] . Eur J Gastroenterol Hepatol , 2021 , 33 ( 10 ): 1316 - 1321 .
Kohsari M , Moradinazar M , Rahimi Z , et al . New inflammatory biomarkers(lymphocyte and monocyte percentage to high-density lipoprotein cholesterol ratio and lymphocyte to monocyte percentage ratio) and their association with some cardiometabolic diseases [J ] . Wien Klin Wochenschr , 2022 , 134 ( 17 ): 626 - 635 .
Sillesen H , Sartori S , Sandholt B , et al . Carotid plaque thickness and carotid plaque burden predict future cardiovascular events in asymptomatic adult Americans [J ] . Eur Heart J Cardiovasc Imaging , 2018 , 19 ( 9 ): 1042 - 1050 .
0
浏览量
1
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621