The clinical value of HDL-C in differentiating patients with alcoholic liver cirrhosis of Child-Turcotte-Pugh grade C
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摘要: 目的 探究高密度脂蛋白胆固醇(high-density lipoprotein cholesterol，HDL-C)区分酒精性肝硬化(alcoholic liver cirrhosis，ALC)患者Child-Turcotte-Pugh(CTP)分级C级的诊断价值。方法 选取2017年1月—2022年2月期间在首都医科大学附属北京地坛医院住院的488例ALC患者为研究对象，其中CTP A/B级患者347例，CTP C级患者141例，记录患者的性别、年龄、实验室指标；通过单因素和多因素二元logistic回归得出区分CTP C级的独立危险因素；绘制受试者工作特征曲线(receiver operating characteristic curve，ROC)，得出曲线下面积(area under the curve，AUC)，并根据约登指数计算cut-off值。结果 CTP C级患者HDL-C水平为0.5(0.3，0.7)mmol/L，低于CTP A/B级患者的HDL-C水平[0.8(0.6，1.1)mmol/L]。通过单因素和多因素logistic回归显示，WBC(OR=1.184，95%CI：1.086~1.291，P < 0.001)，RBC(OR=0.658，95%CI：0.480~0.901，P < 0.001)，AST(OR=1.008，95%CI：1.000~1.016，P=0.044)，HDL-C(OR=0.604，95%CI：0.434~0.841，P < 0.001)是诊断ALC患者肝功能进展到CTP C级的独立危险因素。绘制HDL-C的ROC曲线，得出AUC为0.760，显著高于TC、TG、LDL-C的AUC，分别为0.629、0.589、0.535；根据约登指数得出HDL-C的cut-off值是0.655 mmol/L，以HDL-C 0.655 mmol/L为界值将患者分为低风险组和高风险组，发现低风险组HDL-C患者的肝功能更差。结论 CTP C级ALC患者的HDL-C水平显著低于CTP A/B级患者，HDL-C对CTP分级有一定的参考价值，可以作为ALC患者CTP分级的辅助指标。
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关键词:
- 酒精性肝硬化 /
- 血脂 /
- Child-Turcotte-Pugh分级 /
- 高密度脂蛋白胆固醇
Abstract: Objective To investigate the clinical value of high-density lipoprotein cholesterol(HDL-C) to identify alcoholic liver cirrhosis(ALC) patients in Child-Turcotte-Pugh(CTP) class C.Methods This retrospective study enrolled 488 patients with ALC who were hospitalized in Beijing Ditan Hospital of Capital Medical University between January 2017 and February 2022, including 347 patients with CTP grade A/B, and 141 patients with CTP grade C. Gender, age, and laboratory indexes of the patients were recorded; univariate and multifactorial binary logistic regression was employed to identify independent risk factors for determining CTP classification. The efficacy of these factors was evaluated through the receiver operating characteristic curve(ROC). The area under the curve(AUC) was derived to assess the diagnostic value, and the best cut-off value was calculated based on the Youden index.Results HDL-C levels in CTP class C patients were 0.5(0.3, 0.7)mmol/L, which were lower than CTP class A/B patients(0.8[0.6, 1.1]mmol/L). Through univariate and multivariate logistic regression, WBC(OR=1.184, 95%CI: 1.086-1.291, P < 0.001), RBC(OR=0.658, 95%CI: 0.480-0.901, P < 0.001), AST(OR=1.008, 95%CI: 1.000-1.016, P=0.044) and HDL-C(OR=0.604, 95%CI: 0.434-0.841, P < 0.001) were independent risk factors for the diagnosis of liver function in patients with ALC CTP class C. The AUC of HDL-C was 0.760, which was significantly higher than the AUC of TC(0.629), TG(0.589), and LDL-C(0.535). The cut-off value of HDL-C was 0.655 mmol/L based on the Youden index; with HDL-C ≤0.655 mmol/L as the boundary value patients were divided into low-risk groups and high-risk groups and it was found that patients with low levels of HDL-C had worse liver function.Conclusion HDL-C levels in ALC patients have some reference value for CTP grading, and can be used as an auxiliary index for CTP grading. -
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表 1 不同CTP分级患者的基线情况
M(P25，P75)，例(%)，X±S CTP A/B级(n=347) CTP C级(n=141) 总体(n=488) 年龄/岁 57(51，63) 52(45，58) 56(49，62) 男 343(98.8) 137(97.2) 481(98.6) WBC/(×109/L) 3.8(2.7，5.3) 5.1(3.6，7.5) 4.1(2.9，5.8) RBC/(×109/L) 3.3(2.7，3.9) 2.7(2.3，3.2) 3.1(2.6，3.7) HGB/(g/L) 98.0(75.0，122.0) 92.0(70.5，114.0) 96.0(74.0，118.0) PLT/(×109/L) 79.0(55.0，122.0) 78.0(52.0，111.5) 78.0(54.0，117.8) Cr/(μmol/L) 69.8(59.6，84.8) 69.4(59.3，90.3) 69.7(59.5，85.2) Glu/(mmol/L) 6.0(5.1，7.9) 6.2(5.2，8.0) 6.1(5.1，7.9) ALT/(U/L) 20.3(13.6，29.5) 44.8(15.8，33.3) 20.9(14.2，30.5) AST/(U/L) 30.5(20.9，44.4) 44.8(32.6，72.5) 34.8(23.3，51.0) TBIL/(μmol/L) 20.8(15.0，31.2) 63.0(44.3，99.0) 26.9(16.9，49.7) ALB/(g/L) 32.4(29.2，36.7) 26.8(24.6，28.9) 30.6(27.1，35.1) TC/(mmol/L) 3.1(2.6，3.8) 2.8(2.1，3.6) 3.0(2.4，3.8) TG/(mmol/L) 0.8(0.6，1.1) 0.8(0.5，1.0) 0.8(0.6，1.1) HDL-C/(mmol/L) 0.8(0.6，1.1) 0.5(0.3，0.7) 0.7(0.5，1.0) LDL-C/(mmol/L) 1.8(1.4，2.4) 1.5(1.1，2.0) 1.7(1.3，2.3) INR 1.3(1.2，1.4) 1.8(1.6，1.9) 1.4(1.2，1.6) 
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表 2 单因素和多因素logistic回归分析影响CTP分级的危险因素
指标 单因素 多因素 OR 95%CI P OR 95%CI P INR 6.981 4.637~9.396 < 0.001 WBC 1.223 1.137~1.317 < 0.001 1.184 1.086~1.291 < 0.001 RBC 0.426 0.326~0.557 < 0.001 0.658 0.480~0.901 0.009 HGB 0.990 0.984~0.997 0.006 PLT 0.997 0.994~1.000 0.080 Cr 1.001 0.997~1.004 0.658 Glu 1.026 0.977~1.078 0.305 ALT 1.009 1.001~1.017 0.029 AST 1.011 1.006~1.016 < 0.001 1.008 1.000~1.016 0.044 TBIL 1.065 1.052~1.078 < 0.001 ALB 0.871 0.839~0.905 < 0.001 TC 0.990 0.883~1.110 0.864 TG 1.013 0.953~1.077 0.677 HDL-C 0.037 0.016~0.082 < 0.001 0.604 0.434~0.841 < 0.001 LDL-C 0.622 0.472~0.820 0.001
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表 3 不同CTP分级及高、低风险HDL-C组间肝功能的比较
M(P25，P75) 肝功能指标 CTP C级 CTP A/B级 HDL-C≤0.655 mmol/L HDL-C>0.655
mmol/LP HDL-C≤0.655 mmol/L HDL-C>0.655mmol/L P ALT 23.5(16.6，38.9) 21.3(14.2，27.8) 0.210 19.3(13.2，29.6) 20.6(14.1，29.4) 0.740 AST 49.5(35.2，76.1) 38.9(28.4，49.5) 0.005 32.6(21.4，54.8) 29.9(20.7，41.6) 0.142 TBIL 73.5(47.9，111.7) 53.5(41.9，71.8) 0.012 20.8(15.2，31.7) 20.8(14.7，30.9) 0.826
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[1] World Health Organ. 2018. Alcohol. Fact Sheet, World Health. Organ., Geneva.
https://www.who.int/news-room/fact-sheets/detail/alcohol .[2] 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. 酒精性肝病防治指南(2018年更新版)[J]. 临床肝胆病杂志, 2018, 21(2): 170-176. https://www.cnki.com.cn/Article/CJFDTOTAL-LCGD201805009.htm
[3] Haj Ali S, Abu Sneineh A, Hasweh R. Nutritional assessment in patients with liver cirrhosis[J]. World J Hepatol, 2022, 14(9): 1694-1703. doi: 10.4254/wjh.v14.i9.1694
[4] Gao YY, Yuan HX, Han T, et al. Associations between endoscopic primary prophylaxis and rebleeding in liver cirrhosis patients with esophagogastric variceal bleeding[J]. Front Surg, 2022, 9: 925915. doi: 10.3389/fsurg.2022.925915
[5] Feng RR, Guo XZ, Kou Y, et al. Association of lipid profile with decompensation, liver dysfunction, and mortality in patients with liver cirrhosis[J]. Postgrad Med, 2021, 133(6): 626-638. doi: 10.1080/00325481.2021.1930560
[6] Tauseef A, Zafar M, Rashid B, et al. Correlation of fasting lipid profile in patients with chronic liver disease: a descriptive cross-sectional study in tertiary care hospital[J]. Cureus, 2020, 12(10): e11019.
[7] Privitera G, Spadaro L, Marchisello S, et al. Abnormalities of lipoprotein levels in liver cirrhosis: clinical relevance[J]. Dig Dis Sci, 2018, 63(1): 16-26. doi: 10.1007/s10620-017-4862-x
[8] 徐小元, 丁惠国, 李文刚, 等. 肝硬化诊治指南[J]. 临床肝胆病杂志, 2019, 22(6): 770-786. https://www.cnki.com.cn/Article/CJFDTOTAL-LCGD201911006.htm
[9] Sugimoto K, Takei Y. Pathogenesis of alcoholic liver disease[J]. Hepatol Res, 2017, 47(1): 70-79. doi: 10.1111/hepr.12736
[10] Ambade A, Lowe P, Kodys K, et al. Pharmacological Inhibition of CCR2/5 Signaling Prevents and Reverses Alcohol-Induced Liver Damage, Steatosis, and Inflammation in Mice[J]. Hepatology, 2019, 69(3): 1105-1121. doi: 10.1002/hep.30249
[11] You M, Fischer M, Deeg MA, et al. Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein(SREBP)[J]. J Biol Chem, 2002, 277(32): 29342-29347. doi: 10.1074/jbc.M202411200
[12] Hu M, Wang FM, Li X, et al. Regulation of hepatic lipin-1 by ethanol: role of AMP-activated protein kinase/sterol regulatory element-binding protein 1 signaling in mice[J]. Hepatology, 2012, 55(2): 437-446. doi: 10.1002/hep.24708
[13] Trieb M, Stadlbauer V, Birner-Gruenberger R, et al. Liver disease alters high-density lipoprotein composition, metabolism and function[J]. Atherosclerosis, 2016, 252: e225.
[14] Yu YJ, Raka F, Adeli K. The role of the gut microbiota in lipid and lipoprotein metabolism[J]. J Clin Med, 2019, 8(12): 2227. doi: 10.3390/jcm8122227
[15] Acharya C, Bajaj JS. Gut microbiota and complications of liver disease[J]. Gastroenterol Clin N Am, 2017, 46(1): 155-169. doi: 10.1016/j.gtc.2016.09.013
[16] 石翠翠, 刘彦君, 章瑞南, 等. 肝硬化患者血脂异常分析[J]. 实用肝脏病杂志, 2021, 24(6): 859-862. doi: 10.3969/j.issn.1672-5069.2021.06.023
[17] Chrostek L, Supronowicz L, Panasiuk A, et al. The effect of the severity of liver cirrhosis on the level of lipids and lipoproteins[J]. Clin Exp Med, 2014, 14(4): 417-421. doi: 10.1007/s10238-013-0262-5
[18] Shoaib N, Khan Z, Ibrahim M, et al. Dyslipidemia and impaired liver function biomarkers in patients with hepatitis B liver cirrhosis[J]. J Taibah Univ Med Sci, 2023, 18(4): 748-754.
[19] Unger LW, Forstner B, Schneglberger S, et al. Patterns and prevalence of dyslipidemia in patients with different etiologies of chronic liver disease[J]. Wiener Klinische Wochenschrift, 2019, 131(17-18): 395-403. doi: 10.1007/s00508-019-01544-5
[20] Halsted CH. Nutrition and alcoholic liver disease[J]. Semin Liver Dis, 2004, 24(3): 289-304. doi: 10.1055/s-2004-832941
[21] Marsillach J, Camps J, Ferre N, et al. Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in experimental liver disease[J]. BMC Gastroenterol, 2009, 9: 3. doi: 10.1186/1471-230X-9-3
[22] Aviram M, Rosenblat M, Bisgaier CL, et al. Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase[J]. J Clin Invest, 1998, 101(8): 1581-1590. doi: 10.1172/JCI1649
[23] Marsillach J, Ferre N, Vila MC, et al. Serum paraoxonase-1 in chronic alcoholics: relationship with liver disease[J]. Clin Biochem, 2007, 40(9-10): 645-650. doi: 10.1016/j.clinbiochem.2007.01.020
[24] Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases[J]. Gastroenterology, 2014, 146(6): 1513-1524. doi: 10.1053/j.gastro.2014.01.020
[25] Wang H, Zhou H, Zhang Q, et al. Inhibition of IRAK4 kinase activity improves ethanol-induced liver injury in mice[J]. J Hepatol, 2020, 73(6): 1470-1481. doi: 10.1016/j.jhep.2020.07.016
[26] Jayaraman S, Haupt C, Gursky O. Paradoxical effects of SAA on lipoprotein oxidation suggest a new antioxidant function for SAA[J]. J Lipid Res, 2016, 57(12): 2138-2149. doi: 10.1194/jlr.M071191
[27] Schwedhelm C, Nimptsch K, Bub A, et al. Association between alcohol consumption and serum paraoxonase and arylesterase activities: a cross-sectional study within the Bavarian population[J]. Br J Nutr, 2016, 115(4): 730-736. doi: 10.1017/S0007114515004985
[28] Thabut D, Tazi KA, Bonnefont-Rousselot D, et al. High-density lipoprotein administration attenuates liver proinflammatory response, restores liver endothelial nitric oxide synthase activity, and lowers portal pressure in cirrhotic rats[J]. Hepatology, 2007, 46(6): 1893-1906. doi: 10.1002/hep.21875
[29] Trieb M, Rainer F, Stadlbauer V, et al. HDL-related biomarkers are robust predictors of survival in patients with chronic liver failure[J]. J Hepatol, 2020, 73(1): 113-120. doi: 10.1016/j.jhep.2020.01.026
[30] Selimoglu MA, Aydogdu S, Yagci RV. Lipid parameters in childhood cirrhosis and chronic liver disease[J]. Pediatr Int, 2002, 44(4): 400-403. doi: 10.1046/j.1442-200X.2002.01590.x
[31] Levels JH, Abraham PR, van den Ende A, et al. Distribution and kinetics of lipoprotein-bound endotoxin[J]. Infect Immun, 2001, 69(5): 2821-2828. doi: 10.1128/IAI.69.5.2821-2828.2001
[32] Cheng R, Tan N, Kang Q, et al. High-density lipoprotein cholesterol is a predictor of survival in cirrhotic patients with acute gastrointestinal bleeding: a retrospective study[J]. BMC Gastroenterol, 2020, 20(1): 1-9. doi: 10.1186/s12876-019-1136-4
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