单核细胞/高密度脂蛋白胆固醇与非酒精性脂肪性肝病的相关性分析
DOI: 10.3969/j.issn.1001-5256.2021.05.031
Association between monocyte-to-high-density lipoprotein cholesterol ratio and nonalcoholic fatty liver disease
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摘要:
目的 探讨单核细胞/高密度脂蛋白胆固醇(MHR)与非酒精性脂肪性肝病(NAFLD)的关系。 方法 选取2018年1月—2020年10月入住大连大学附属中山医院消化内科并经腹部CT诊断为NAFLD的208例患者作为NAFLD组,另选取同期210例健康体检人群设为对照组。所有受试者均行血常规、生化及腹部CT检查,计算血清MHR水平。另外,根据腹部CT的影像学结果,将NAFLD患者分为轻度NAFLD组(n=148)及中重度NAFLD组(n=60),观察不同程度NAFLD患者与对照组WBC及MHR等指标的差异。正态分布计量资料两组间比较采用独立样本t检验,多组间比较采用单因素方差分析。偏态分布计量资料两组间比较采用Mann-Whitney U秩和检验,多组间采用Kruskal-Wallis H检验。计数资料两组间比较采用四格表χ2检验,3组间比较采用R×C表χ2检验。MHR与各代谢指标及NAFLD严重程度间的相关性采用Spearman相关分析。绘制受试者工作特征曲线评估MHR对NAFLD的诊断价值。 结果 与对照组相比,NAFLD组中的体质量(t=-10.573, P < 0.001)、BMI(t=-13.112, P < 0.001)、吸烟史(χ2=14.667, P < 0.001)、WBC(t=-7.359, P < 0.001)、单核细胞(Z=-9.932, P < 0.001)、LDL-C(t=-3.394, P=0.001)、TG(Z=-11.737, P < 0.001)、CHO(t=-2.985, P=0.003)、空腹血糖(Z=-7.827, P < 0.001)、ALT(Z=-12.583, P < 0.001)、AST(Z=-9.514, P < 0.001) 水平均增加,而血清HDL-C(t=10.440, P < 0.001)水平下降;另外,MHR水平存在性别差异,男性明显高于女性,差异有统计学意义(P < 0.001)。与对照组及轻度NAFLD组相比,血清MHR水平在中重度NAFLD组中显著升高,差异有统计学意义(P值均 < 0.001)。相关分析结果提示血清MHR水平与HDL-C呈负相关(r=-0.565, P < 0.001),与吸烟史、体质量、BMI、WBC、单核细胞、TG、空腹血糖、ALT、AST呈正相关(r值分别为0.449、0.482、0.430、0.478、0.892、0.333、0.157、0.386、0.281,P值均 < 0.01)。同时,MHR水平与NAFLD严重程度呈正相关(r=0.629,P < 0.001)。ROC曲线表明MHR曲线下面积为0.846(95%CI:0.810~0.882,P < 0.001),敏感度和特异度分别为77.9%和74.3%。 结论 血清MHR水平与NAFLD相关,可作为评价NAFLD病情进展的一种预测指标。 Abstract:Objective To investigate the association between monocyte-to-high-density lipoprotein cholesterol ratio (MHR) and nonalcoholic fatty liver disease (NAFLD). Methods A total of 208 patients who were admitted to Department of Gastroenterology, Zhongshan Hospital Affiliated to Dalian University, from January 2018 to October 2020 and were diagnosed with NAFLD by abdominal CT were enrolled as NAFLD group, and 210 healthy individuals were enrolled as control group. All subjects underwent routine blood test, biochemical examination, and abdominal CT examination, and serum MHR was calculated. In addition, according to abdominal CT findings, the patients with NAFLD were divided into mild NAFLD group with 148 patients and moderate-to-severe NAFLD group with 60 patients, and the variables such as white blood cell count (WBC) and MHR were compared between the three groups. The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and a one-way analysis of variance was used for comparison between multiple groups; the Mann-Whitney U test was used for comparison of data with skewed distribution between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups. The fourfold table chi-square test was used for comparison of categorical data between two groups, and the R×C table chi-square test was used for comparison between three groups. A Spearman correlation analysis was used to investigate the correlation of MHR with metabolic markers and the severity of NAFLD. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of MHR in predicting NAFLD. Results Compared with the control group, the NAFLD group had significant increases in body weight (t=-10.573, P < 0.001), body mass index (BMI) (t=-13.112, P < 0.001), smoking history (Z=14.667, P < 0.001), WBC (t=-7.359, P < 0.001), monocytes (Z=-9.932, P < 0.001), low-density lipoprotein cholesterol (t=-3.394, P=0.001), triglyceride (TG) (Z=-11.737, P < 0.001), cholesterol (t=-2.985, P=0.003), fasting blood glucose (FBG) (Z=-7.827, P < 0.001), alanine aminotransferase (ALT) (Z=-12.583, P < 0.001), and aspartate aminotransferase (AST) (Z=-9.514, P < 0.001) and a significant reduction in serum high-density lipoprotein cholesterol (HDL-C) (t=10.440, P < 0.001); in addition, MHR level had gender differences, and male patients had a significantly higher level than female patients (P < 0.001). Compared with the control group and the mild NAFLD group, the moderate-to-severe NAFLD group had a significant increase in serum MHR level (P < 0.001). The correlation analysis showed that serum MHR level was negatively correlated with HDL-C (r=-0.565, P < 0.001) and were positively correlated with smoking history, body weight, BMI, WBC, monocytes, TG, FBG, ALT, and AST (r=0.449, 0.482, 0.430, 0.478, 0.892, 0.333, 0.157, 0.386, and 0.281, all P < 0.01). At the same time, MHR level was positively correlated with the severity of NAFLD (r=0.629, P < 0.001). The ROC curve showed that MHR had an area under the ROC curve of 0.846 (95% confidence interval: 0.810-0.882, P < 0.001), with a sensitivity of 77.9% and a specificity of 74.3%. Conclusion Serum MHR level is associated with NAFLD and can be used as a predictive index for evaluating the progression of NAFLD. -
Key words:
- Non-alcoholic Fatty Liver Disease /
- Monocytes /
- Cholesterol, HDL
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表 1 对照组与NAFLD组患者一般情况的比较
指标 对照组(n=210) NAFLD组(n=208) 统计值 P值 男/女(例) 95/115 114/94 χ2=3.828 >0.050 年龄(岁) 52(44~61) 55(43~62) Z=-1.066 0.286 吸烟[例(%)] 30(14.29) 62(29.81) χ2=14.667 < 0.001 身高(cm) 167(162~172) 170(162~175) Z=-1.891 0.059 体质量(kg) 64.64±10.83 77.80±14.35 t=-10.573 < 0.001 BMI(kg/m2) 22.88±2.87 27.03±3.56 t=-13.112 < 0.001 WBC(×109/L) 5.11±1.14 6.00±1.31 t=-7.359 < 0.001 单核细胞(×109/L) 0.16(0.13~0.20) 0.23(0.20~0.30) Z=-9.932 < 0.001 HDL-C(mmol/L) 1.45±0.30 1.18±0.22 t=10.440 < 0.001 MHR 0.12(0.08~0.16) 0.20(0.16~0.25) Z=-12.233 < 0.001 LDL-C(mmol/L) 2.88±0.68 3.13±0.78 t=-3.394 0.001 TG(mmol/L) 1.15(0.87~1.44) 1.92(1.49~2.86) Z=-11.737 < 0.001 CHO(mmol/L) 4.99±0.90 5.28±1.02 t=-2.985 0.003 FBG(mmol/L) 4.88(4.55~5.21) 5.34(4.89~6.06) Z=-7.827 < 0.001 ALT(U/L) 16.0(12.0~24.0) 36.0(25.0~54.5) Z=-12.583 < 0.001 AST(U/L) 18.00(15.00~21.00) 24.00(18.00~30.75) Z=-9.514 < 0.001 表 2 对照组与不同程度NAFLD患者一般情况的比较
指标 对照组(n=210) 轻度NAFLD组(n=148) 中重度NAFLD组(n=60) 统计值 P值 男/女(例) 95/115 75/73 39/21 χ2=7.332 0.026 年龄(岁) 51.40±11.78 53.61±11.50 50.43±13.32 F=2.141 0.119 吸烟[例(%)] 30(14.29) 36(24.32) 26(43.33) H=23.654 < 0.001 身高(cm) 167.0(162.0~172.0) 169.0(161.3~175.0) 170.5(162.0~177.0) H=5.292 0.071 体质量(kg) 64.64±10.83 76.67±12.84 80.60±17.36 F=58.503 < 0.001 BMI(kg/m2) 22.88±2.87 26.81±3.18 27.58±4.35 F=129.920 < 0.001 WBC(×109/L) 5.11±1.14 5.79±1.17 6.51±1.49 F=54.130 < 0.001 单核细胞(×109/L) 0.16(0.13~0.20) 0.21(0.19~0.26) 0.30(0.22~0.35) H=115.697 < 0.001 HDL-C(mmol/L) 1.45±0.30 1.21±0.23 1.13±0.19 F=88.936 < 0.001 MHR 0.12(0.08~0.16) 0.19(0.15~0.22) 0.26(0.20~0.32) H=167.607 < 0.001 LDL-C(mmol/L) 2.88±0.68 3.18±0.79 2.99±0.75 F=7.180 0.001 TG(mmol/L) 1.15(0.87~1.44) 1.91(1.53~2.82) 1.96(1.45~3.11) H=137.865 < 0.001 CHO(mmol/L) 4.99±0.90 5.33±0.99 5.14±1.11 F=5.278 0.005 FBG(mmol/L) 4.88(4.55~5.21) 5.34(4.87~6.05) 5.35(4.94~6.06) H=61.521 < 0.001 ALT(U/L) 16.00(12.00~24.00) 32.00(21.78~50.00) 46.00(32.35~60.75) H=167.151 < 0.001 AST(U/L) 18.00(15.00~21.00) 23.00(17.25~29.00) 24.50(21.00~33.75) H=95.963 < 0.001 表 3 血清MHR水平与各变量的相关性
变量 r值 P值 年龄 -0.094 0.054 吸烟史 0.449 < 0.001 体质量 0.482 < 0.001 BMI 0.430 < 0.001 WBC 0.478 < 0.001 单核细胞 0.892 < 0.001 HDL-C -0.565 < 0.001 LDL-C 0.013 0.781 TG 0.333 < 0.001 CHO -0.071 0.145 FBG 0.157 0.001 ALT 0.386 < 0.001 AST 0.281 < 0.001 NAFLD严重性 0.629 < 0.001 -
[1] ESLAM M, SANYAL AJ, GEORGE J, et al. MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease[J]. Gastroenterology, 2020, 158(7): 1999-2014. e1. DOI: 10.1053/j.gastro.2019.11.312. [2] YILMAZ M, KAYANÇIÇEK H. A new inflammatory marker: Elevated monocyte to HDL cholesterol ratio associated with smoking[J]. J Clin Med, 2018, 7(4): 76. DOI: 10.3390/jcm7040076. [3] 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. DOI: 10.2217/bmm-2018-0048. [4] KAPLAN IG, KAPLAN M, ABACIOGLU OO, et al. Monocyte/HDL ratio predicts hypertensive complications[J]. Bratisl Lek Listy, 2020, 121(2): 133-136. DOI: 10.4149/BLL_2020_018. [5] USTA A, AVCI E, BULBUL CB, et al. The monocyte counts to hdlcholesterol ratio in obese and lean patients with polycystic ovary syndrome[J]. Reprod Biol Endocrinol, 2018, 16 (1): 34. DOI: 10.1186/s12958-018-0351-0. [6] VAHIT D, AKBOGA MK, SAMET Y, et al. Assessment of monocyte to high density lipoprotein cholesterol ratio and lymphocyte-to-monocyte ratio in patients with metabolic syndrome[J]. Biomark Med, 2017, 11(7): 535-540. DOI: 10.2217/bmm-2016-0380. [7] Chinese Medical Association Liver Diseases Branch Fatty Liver and Alcoholic Liver Disease Group, Guidelines for the prevention and treatment of nonalcoholic fatty liver disease (updated version 2018) [J]. J Clin Hepatol, 2018, 34(5): 947-957. DOI: 10.3969/j.issn.1001-5256.2018.05.007.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防治指南(2018年更新版)[J]. 临床肝胆病杂志, 2018, 34(5): 947-957. DOI: 10.3969/j.issn.1001-5256.2018.05.007. [8] ALSWAT KA, FALLATAH HI, AL-JUDAIBI B, et al. Position statement on the diagnosis and management of non-alcoholic fatty liver disease[J]. Saudi Med J, 2019, 40(6): 531-540. DOI: 10.15537/smj.2019.6.23980. [9] MALIAKKAL BJ. Pathogenesis of non-alcoholic fatty liver disease and implications on cardiovascular outcomes in liver transplantation[J]. Transl Gastroenterol Hepatol, 2020, 5: 36. DOI: 10.21037/tgh.2019.12.02. [10] SHAO M, YE Z, QIN Y, et al. Abnormal metabolic processes involved in the pathogenesis of non-alcoholic fatty liver disease (Review)[J]. Exp Ther Med, 2020, 20(5): 26. DOI: 10.3892/etm.2020.9154. [11] WANG S, ZHANG C, ZHANG G, et al. Association between white blood cell count and non-alcoholic fatty liver disease in urban Han Chinese: A prospective cohort study[J]. BMJ Open, 2016, 6(6): e010342. DOI: 10.1136/bmjopen-2015-010342. [12] ZHANG J, CHEN W, FANG L, et al. Increased intermediate monocyte fraction in peripheral blood is associated with nonalcoholic fatty liver disease[J]. Wien Klin Wochenschr, 2018, 130(11-12): 390-397. DOI: 10.1007/s00508-018-1348-6. [13] WANG HY, SHI WR, YI X, et al. Assessing the performance of monocyte to high-density lipoprotein ratio for predicting ischemic stroke: Insights from a population-based Chinese cohort[J]. Lipids Health Dis, 2019, 18(1): 127. DOI: 10.1186/s12944-019-1076-6. [14] LI N, REN L, WANG JH, et al. Relationship between monocyte to HDL cholesterol ratio and concomitant cardiovascular disease in Chinese Han patients with obstructive sleep apnea[J]. Cardiovasc Diagn Ther, 2019, 9(4): 362-370. DOI: 10.21037/cdt.2019.08.02. [15] JIALAL I, JIALAL G, ADAMS-HUET B, et al. Neutrophil and monocyte ratios to high-density lipoprotein-cholesterol and adiponectin as biomarkers of nascent metabolic syndrome[J]. Horm Mol Biol Clin Investig, 2020, 41(2). DOI: 10.1515/hmbci-2019-0070. [16] ANCUTA P, WANG J, GABUZDA D. CD16+ monocytes produce IL-6, CCL2, and matrix metalloproteinase-9 upon interaction with CX3CL1-expressing endothelial cells[J]. J Leukoc Biol, 2006, 80(5): 1156-1164. DOI: 10.1189/jlb.0206125. [17] CHA JY, KIM DH, CHUN KH. The role of hepatic macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[J]. Lab Anim Res, 2018, 34(4): 133-139. DOI: 10.5625/lar.2018.34.4.133. [18] MCMAHAN RH, WANG XX, CHENG LL, et al. Bile acid receptor activation modulates hepatic monocyte activity and improves nonalcoholic fatty liver disease[J]. J Biol Chem, 2013, 288(17): 11761-11770. DOI: 10.1074/jbc.M112.446575. [19] GLASS CK, OLEFSKY JM. Inflammation and lipid signaling in the etiology of insulin resistance[J]. Cell Metab, 2012, 15(5): 635-645. DOI: 10.1016/j.cmet.2012.04.001.