中文|English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

血清脂联素、视黄醇结合蛋白4及中性粒细胞/淋巴细胞比值对代谢相关脂肪性肝炎的诊断价值

魏燕娇,  雷俊杰,  郭剑津

引用本文:
Citation:

血清脂联素、视黄醇结合蛋白4及中性粒细胞/淋巴细胞比值对代谢相关脂肪性肝炎的诊断价值

DOI: 10.12449/JCH260913
基金项目: 

山西省基础研究计划项目 (202303021221198)

伦理学声明:本研究方案于2023年1月6日经由山西白求恩医院/山西医学科学院医学伦理委员会审批通过,伦理批号:YXLL-2023-011,所纳入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:魏燕娇负责课题设计,资料分析,撰写论文;魏燕娇、雷俊杰参与收集数据,修改论文;魏燕娇、郭剑津负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    郭剑津, 15135184838@139.com (ORCID: 0009-0008-7473-1371)

Value of serum adiponectin, retinol-binding protein 4, and neutrophil-to-lymphocyte ratio in the diagnosis of metabolic dysfunction-associated steatohepatitis

Research funding: 

Shanxi Basic Research Project (202303021221198)

More Information
  • 摘要:   目的  分析血清脂联素(ADPN)、视黄醇结合蛋白4(RBP4)及中性粒细胞/淋巴细胞比值(NLR)对代谢相关脂肪性肝炎(MASH)的评估价值,为临床预防提供参考。  方法  选取2023年1月—2025年1月于山西医科大学第三医院就诊的代谢相关脂肪性肝病(MAFLD)患者为研究对象,采用Logistic回归分析MASH的预测因素,采用R语言rms程序包建立列线图,绘制受试者操作特征曲线(ROC曲线)、校准曲线及决策曲线分析(DCA)评估模型的准确性和实用性,并采用Pearson相关性分析各指标间的相关性。计数资料两组间比较采用χ2检验;符合正态分布的计量资料两组间比较采用成组t检验;不符合正态分布的计量资料两组间比较采用Mann-Whitney U检验。  结果  共纳入298例MAFLD患者,其中MASH患者95例,单纯性脂肪变性患者203例。多因素Logistic回归分析显示,丙氨酸氨基转移酶(ALT)、碱性磷酸酶(ALP)、RBP4、ADPN及NLR是MASH的独立影响因素(P值均<0.05)。根据以上因素构建列线图模型并进行评估,ROC曲线结果显示,模型的曲线下面积为0.985(95%置信区间:0.976~0.995),灵敏度为0.968,特异度为0.901。校准曲线结果显示,H-L拟合优度检验(χ2=2.905,P=0.940)提示该模型预测概率与实际概率之间的差异无统计学意义,表明该模型拟合性良好、预测准确度较高。DCA结果显示,当预测风险阈值>0.05时,该模型可获得净收益。Pearson相关性分析显示,MASH患者血清RBP4与ADPN呈负相关(r=-0.275,P<0.001),与NLR呈正相关(r=0.282,P<0.001);ADPN与NLR呈负相关(r=-0.221,P<0.001)。  结论  ALT、ALP、RBP4、ADPN及NLR是MASH发生的独立影响因素,临床应加强监测,早期识别高风险患者并及时干预,以降低其发病率及疾病进展风险。

     

  • 注: ALT,丙氨酸氨基转移酶;ALP,碱性磷酸酶;ADPN,脂联素;RBP4,视黄醇结合蛋白4;NLR,中性粒细胞/淋巴细胞比值;MASH,代谢相关脂肪性肝炎。

    图  1  MASH疾病预测模型的建立

    Figure  1.  Establishment of MASH disease prediction system

    注: a,ROC曲线;b,校准曲线;c,DCA曲线。ROC曲线,受试者操作特征曲线;DCA,决策曲线分析;MASH,代谢相关脂肪性肝炎;AUC,曲线下面积;CI,置信区间。

    图  2  MASH疾病预测模型的评估

    Figure  2.  Evaluation of MASH disease prediction model

    注: a,RBP4与ADPN的相关性;b,RBP4与NLR的相关性;c,ADPN与NLR的相关性。ADPN,脂联素;RBP4,视黄醇结合蛋白4;NLR,中性粒细胞/淋巴细胞比值;MASH,代谢相关脂肪性肝炎。

    图  3  MASH患者血清RBP4、ADPN、NLR相关性分析

    Figure  3.  Correlation analysis of serum RBP4, ADPN and NLR in MASH patients

    表  1  两组临床资料及实验室指标比较

    Table  1.   Comparison of clinical data and laboratory indicators between the two groups

    因素 MASH组(n=95) SFL组(n=203) 统计值 P值
    性别[例(%)] χ2=0.473 0.492
    男 55(57.89) 126(62.07)
    女 40(42.11) 77(37.93)
    年龄(岁) 51.36±6.59 50.24±6.95 t=1.318 0.189
    BMI(kg/m2) 26.86±4.21 24.93±4.07 t=3.773 <0.001
    吸烟史[例(%)] χ2=0.165 0.685
    是 52(54.74) 106(52.22)
    否 43(45.26) 97(47.78)
    伴糖尿病[例(%)] χ2=0.521 0.471
    是 44(46.32) 85(41.87)
    否 51(53.68) 118(58.13)
    伴高血压[例(%)] χ2=0.336 0.562
    是 46(48.42) 91(44.83)
    否 49(51.58) 112(55.17)
    ALT(U/L) 45.23±11.57 30.31±9.68 t=11.633 <0.001
    AST(U/L) 24.22±6.59 23.09±6.13 t=1.448 0.149
    ALP(U/L) 101.39±12.27 82.37±10.43 t=13.850 <0.001
    GGT(U/L) 63.58±11.23 66.16±12.65 t=1.699 0.090
    TBil(μmol/L) 14.00(12.00~16.00) 14.00(12.00~16.00) Z=-0.797 0.425
    DBil(μmol/L) 5.00(4.00~7.00) 5.00(4.00~7.00) Z=-0.368 0.713
    TG(mmol/L) 3.45±1.10 3.21±0.95 t=1.931 0.055
    TC(mmol/L) 5.23±0.98 5.18±0.99 t=0.408 0.684
    HDL-C(mmol/L) 1.22±0.30 1.28±0.32 t=1.538 0.125
    LDL-C(mmol/L) 3.84±0.91 3.63±0.91 t=1.856 0.064
    ADPN(μg/mL) 9.13±2.05 11.58±2.43 t=8.510 <0.001
    RBP4(mg/L) 25.00(22.00~27.00) 19.00(17.00~22.00) Z=-10.625 <0.001
    NLR 1.65±0.45 1.21±0.35 t=9.204 <0.001
    PLT(×109/L) 7.00(6.00~8.00) 7.00(6.00~8.00) Z=-1.256 0.209

    注:MASH,代谢相关脂肪性肝炎;SFL,单纯性脂肪变性;BMI,体重指数;ALT,丙氨酸氨基转移酶;AST,天冬氨酸氨基转移酶;ALP,碱性磷酸酶;GGT,γ-谷氨酰转移酶;TBil,总胆红素;DBil,直接胆红素;TG,甘油三酯;TC,总胆固醇;HDL-C,高密度脂蛋白胆固醇;LDL-C,低密度脂蛋白胆固醇;ADPN,脂联素;RBP4,视黄醇结合蛋白4;NLR,中性粒细胞/淋巴细胞比值;PLT,血小板。

    下载: 导出CSV

    表  2  MASH预测指标的Logistic多因素分析

    Table  2.   Multi-factor analysis of MASH predictors

    自变量 B值 SE Wald P值 OR 95%CI
    BMI 0.005 0.067 0.005 0.945 0.995 0.873~1.135
    ALT 0.112 0.031 13.295 <0.001 1.118 1.053~1.188
    ALP 0.142 0.033 18.011 <0.001 1.152 1.079~1.230
    ADPN -0.550 0.146 14.181 <0.001 0.577 0.434~0.768
    RBP4 0.502 0.108 21.752 <0.001 1.651 1.337~2.039
    NLR 3.911 1.004 15.192 <0.001 49.971 6.991~357.209
    常量 -28.798 5.246 30.134 0.002 <0.001 —

    注:BMI,体重指数;ALT,丙氨酸氨基转移酶;ALP,碱性磷酸酶;ADPN,脂联素;RBP4,视黄醇结合蛋白4;NLR,中性粒细胞/淋巴细胞比值;MASH,代谢相关脂肪性肝炎;OR,比值比;CI,置信区间;SE,标准误。

    下载: 导出CSV
  • [1] Fang J, Yu C H, Li X J, et al. Gut dysbiosis in nonalcoholic fatty liver disease: Pathogenesis, diagnosis, and therapeutic implications[J]. Front Cell Infect Microbiol, 2022, 12: 997018. DOI: 10.3389/fcimb.2022.997018.
    [2] Lv K X, Zhou R, Gu Y P, et al. Status and factors influencing health-related quality of life in patients with non-alcoholic fatty liver disease in Hangzhou: A cross-sectional study[J]. BMJ Open, 2025, 15( 3): e088357. DOI: 10.1136/bmjopen-2024-088357.
    [3] Grander C, Grabherr F, Tilg H. Non-alcoholic fatty liver disease: Pathophysiological concepts and treatment options[J]. Cardiovasc Res, 2023, 119( 9): 1787- 1798. DOI: 10.1093/cvr/cvad095.
    [4] Musso G, Saba F, Cassader M, et al. Lipidomics in pathogenesis, progression and treatment of nonalcoholic steatohepatitis(NASH): Recent advances[J]. Prog Lipid Res, 2023, 91: 101238. DOI: 10.1016/j.plipres.2023.101238.
    [5] Tong Jing, Zhang Keli, Li Changping. Diagnostic performance of serum proneurotensin level and micro RNA load in patients with nonalcoholic steatohepatitis[J]. J Pract Hepatol, 2024, 27( 2): 202- 205. DOI: 10.3969/j.issn.1672-5069.2024.02.011.

    童静, 张珂瓈, 李昌平. 非酒精性脂肪性肝炎患者血清前神经降压素和微小RNA-122水平变化及其诊断脂肪性肝炎的价值探讨[J]. 实用肝脏病杂志, 2024, 27( 2): 202- 205. DOI: 10.3969/j.issn.1672-5069.2024.02.011.
    [6] Mavilia M G, Wu G Y. Liver and serum adiponectin levels in non-alcoholic fatty liver disease[J]. J Dig Dis, 2021, 22( 4): 214- 221. DOI: 10.1111/1751-2980.12980.
    [7] Huang H K, Xu C F. Retinol-binding protein-4 and nonalcoholic fatty liver disease[J]. Chin Med J, 2022, 135( 10): 1182- 1189. DOI: 10.1097/CM9.0000000000002135.
    [8] Liu C F, Chien L W. Predictive role of neutrophil-percentage-to-albumin ratio(NPAR) in nonalcoholic fatty liver disease and advanced liver fibrosis in nondiabetic US adults: Evidence from NHANES 2017-2018[J]. Nutrients, 2023, 15( 8): 1892. DOI: 10.3390/nu15081892.
    [9] Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association; Fatty Liver Expert Committee, Chinese Medical Doctor Association. Guidelines of prevention and treatment for nonalcoholic fatty liver disease: A 2018 update[J]. J Pract Hepatol, 2018, 21( 2): 177- 186. DOI: 10.3969/j.issn.1672-5069.2018.02.007.

    中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会. 非酒精性脂肪性肝病防治指南(2018年更新版)[J]. 实用肝脏病杂志, 2018, 21( 2): 177- 186. DOI: 10.3969/j.issn.1672-5069.2018.02.007.
    [10] Fatty Liver and Alcoholic Liver Disease Group of Chinese Society of Hepatology. Guidelines for management of nonalcoholic fatty liver disease: An updated and revised edition[J]. Chin J Gastroenterol Hepatol, 2010, 19( 6): 483- 487.

    中华医学会肝病学分会脂肪肝和酒精性肝病学组. 非酒精性脂肪性肝病诊疗指南(2010年修订版)[J]. 胃肠病学和肝病学杂志, 2010, 19( 6): 483- 487.
    [11] Han S K, Baik S K, Kim M Y. Non-alcoholic fatty liver disease: Definition and subtypes[J]. Clin Mol Hepatol, 2023, 29( Suppl): S5- S16. DOI: 10.3350/cmh.2022.0424.
    [12] Rong L, Zou J Y, Ran W, et al. Advancements in the treatment of non-alcoholic fatty liver disease(NAFLD)[J]. Front Endocrinol, 2022, 13: 1087260. DOI: 10.3389/fendo.2022.1087260.
    [13] Shen Yue, Zhu Ning, Wang Hai. Diagnostic performance of FibroTouch parameters in the diagnosis of non-alcoholic steatohepatitis[J]. J Pract Hepatol, 2025, 28( 1): 60- 63. DOI: 10.3969/j.issn.1672-5069.2025.01.016.

    沈玥, 朱宁, 王海. FibroTouch检测参数诊断非酒精性脂肪性肝炎患者效能分析[J]. 实用肝脏病杂志, 2025, 28( 1): 60- 63. DOI: 10.3969/j.issn.1672-5069.2025.01.016.
    [14] Liu B, Zheng H, Liu G H, et al. Adiponectin is inversely associated with insulin resistance in adolescents with nonalcoholic fatty liver disease[J]. Endocr Metab Immune Disord Drug Targets, 2022, 22( 6): 631- 639. DOI: 10.2174/1871530321666210927153831.
    [15] Karamfilova V, Gateva A, Alexiev A, et al. The association between retinol-binding protein 4 and prediabetes in obese patients with nonalcoholic fatty liver disease[J]. Arch Physiol Biochem, 2022, 128( 1): 217- 222. DOI: 10.1080/13813455.2019.1673429.
    [16] Cucoranu D C, Pop M, Niculescu R, et al. The association of nonalcoholic fatty liver disease with neutrophil-to-lymphocyte ratio and neutrophil-percentage-to-albumin ratio[J]. Cureus, 2023, 15( 6): e41197. DOI: 10.7759/cureus.41197.
    [17] Hao Lei, Gao Weidong, Hu Juanjuan, et al. Changes of serum adiponectin, vitamin D and apolipoprotein B levels in patients with nonalcoholic fatty liver disease[J]. J Pract Hepatol, 2023, 26( 2): 189- 192. DOI: 10.3969/j.issn.1672-5069.2023.02.010.

    郝蕾, 高卫东, 胡娟娟, 等. 非酒精性脂肪性肝病患者血清脂联素、维生素D和载脂蛋白B水平变化及其临床意义探讨[J]. 实用肝脏病杂志, 2023, 26( 2): 189- 192. DOI: 10.3969/j.issn.1672-5069.2023.02.010.
    [18] Zhan Qirui, Duan Taimei, Yan Jie. Changes of serum amyloid A, plasma heme oxygenase-1 and bone morphogenetic protein 9 levels in patients with nonalcoholic fatty liver diseases[J]. J Pract Hepatol, 2023, 26( 3): 348- 351. DOI: 10.3969/j.issn.1672-5069.2023.03.012.

    湛栖睿, 段太美, 闫洁. 非酒精性脂肪性肝病患者血清淀粉样蛋白A、血浆血红素氧合酶1和骨形成蛋白9水平变化及其临床意义探讨[J]. 实用肝脏病杂志, 2023, 26( 3): 348- 351. DOI: 10.3969/j.issn.1672-5069.2023.03.012.
    [19] Lonardo A. Alanine aminotransferase predicts incident steatotic liver disease of metabolic etiology: Long life to the old biomarker![J]. World J Gastroenterol, 2024, 30( 24): 3016- 3021. DOI: 10.3748/wjg.v30.i24.3016.
    [20] Ferrannini G, Rosenthal N, Hansen M K, et al. Liver function markers predict cardiovascular and renal outcomes in the CANVAS Program[J]. Cardiovasc Diabetol, 2022, 21( 1): 127. DOI: 10.1186/s12933-022-01558-w.
    [21] Tamber S S, Bansal P, Sharma S, et al. Biomarkers of liver diseases[J]. Mol Biol Rep, 2023, 50( 9): 7815- 7823. DOI: 10.1007/s11033-023-08666-0.
    [22] Zhong Xin, Yu Hana, Huang Qingzhi, et al. Correlation between retinol binding protein 4, visfatin and nonalcoholic fatty liver disease[J]. Mod Prev Med, 2021, 48( 8): 1528- 1532. DOI: 10.20043/j.cnki.mpm.2021.08.042.

    钟新, 虞哈娜, 黄清志, 等. 视黄醇结合蛋白4和内脂素与非酒精性脂肪肝的相关性研究[J]. 现代预防医学, 2021, 48( 8): 1528- 1532. DOI: 10.20043/j.cnki.mpm.2021.08.042.
    [23] Yin Huifen, Yu Hongyan, Liu Zhiping. Changes of serum leptin, retinol-binding protein-4 and cholinesterase levels in patients with NAFLD and T2DM[J]. J Pract Hepatol, 2023, 26( 4): 500- 503. DOI: 10.3969/j.issn.1672-5069.2023.04.012.

    尹会芬, 于红艳, 刘志平. 非酒精性脂肪性肝病合并2型糖尿病患者血清瘦素、视黄醇结合蛋白4和胆碱酯酶水平变化及其临床意义研究[J]. 实用肝脏病杂志, 2023, 26( 4): 500- 503. DOI: 10.3969/j.issn.1672-5069.2023.04.012.
    [24] Zhou Lin, Wang Yonghai, Song Xiaofeng, et al. Observation on serum levels of non-HDL, RBP, RBP-4 and adiponectin in patients with type 2 diabetes mellitus and nonalcoholic fatty liver[J]. J Clin Exp Med, 2023, 22( 8): 813- 817. DOI: 10.3969/j.issn.1671-4695.2023.08.008.

    周林, 王永海, 宋晓锋, 等. 2型糖尿病合并非酒精性脂肪肝患者血清non-HDL、RBP、RBP-4及脂联素水平观察[J]. 临床和实验医学杂志, 2023, 22( 8): 813- 817. DOI: 10.3969/j.issn.1671-4695.2023.08.008.
    [25] Ryu J, Hadley J T, Li Z, et al. Adiponectin alleviates diet-induced inflammation in the liver by suppressing MCP-1 expression and macrophage infiltration[J]. Diabetes, 2021, 70( 6): 1303- 1316. DOI: 10.2337/db20-1073.
    [26] Zhou Baocang, Cao Yawei, Wang Qian. Value of serum ADPN and HGF levels in the diagnosis of non-alcoholic fatty liver disease[J]. J Southeast Univ Med Sci Ed, 2024, 43( 5): 698- 703. DOI: 10.3969/j.issn.1671-6264.2024.05.007.

    周保仓, 曹亚伟, 王倩. 血清脂联素、肝细胞生长因子水平对非酒精性脂肪肝的诊断价值[J]. 东南大学学报(医学版), 2024, 43( 5): 698- 703. DOI: 10.3969/j.issn.1671-6264.2024.05.007.
    [27] Yan Meizhu, Huang Jiying, An Min, et al. Study on the application value of neutrophil-lymphocyte ratio in metabolic associated fatty liver disease with liver fibrosis[J]. Int J Lab Med, 2022, 43( 15): 1849- 1853, 1858. DOI: 10.3969/j.issn.1673-4130.2022.15.013.

    颜美珠, 黄继英, 安敏, 等. NLR在代谢相关脂肪性肝病肝纤维化中的应用价值研究[J]. 国际检验医学杂志, 2022, 43( 15): 1849- 1853, 1858. DOI: 10.3969/j.issn.1673-4130.2022.15.013.
    [28] Xiong Feixiang, Meng Peipei, Jiang Yuyong, et al. Clinical value of C-reactive protein/albumin ratio in the diagnosis of alcoholic cirrhosis with spontaneous bacterial peritonitis[J]. J Clin Hepatol, 2023, 39( 8): 1880- 1885. DOI: 10.3969/j.issn.1001-5256.2023.08.017.

    熊飞翔, 孟培培, 江宇泳, 等. C反应蛋白与白蛋白比值对酒精性肝硬化合并自发性细菌性腹膜炎的诊断价值[J]. 临床肝胆病杂志, 2023, 39( 8): 1880- 1885. DOI: 10.3969/j.issn.1001-5256.2023.08.017.
  • 加载中
图(3) / 表(2)
计量
  • 文章访问数:  15
  • HTML全文浏览量:  5
  • PDF下载量:  0
  • 被引次数: 0
出版历程
  • 收稿日期:  2026-02-10
  • 录用日期:  2026-04-28
  • 出版日期:  2026-09-25
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回