血清肝纤维化指标对肝纤维化的诊断价值

张宇; 唐世孝

doi:10.3969/j.issn.1001-5256.2019.11.016

血清肝纤维化指标对肝纤维化的诊断价值

DOI: 10.3969/j.issn.1001-5256.2019.11.016

张宇,
唐世孝

1. 西南医科大学临床医学院
2. 西南医科大学附属医院消化内科

基金项目:

四川省泸州市人民政府—四川医科大学科技战略合作项目[2015LZCYD-S01(9/15)]；

详细信息

中图分类号: R575.2
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出版历程
- 收稿日期: 2019-06-03
- 出版日期: 2019-11-20

Value of serum liver fibrosis markers in the diagnosis of liver fibrosis

School of Clinical Medicine,Southwest Medical University

Research funding:

摘要

摘要: 目的探讨血清肝纤维化指标Ⅲ型前胶原蛋白（PCⅢ）、Ⅳ型胶原蛋白（C-Ⅳ）、透明质酸（HA）、层粘连蛋白（LN）,即肝纤维化四项对肝纤维化诊断的价值。方法回顾性分析2018年4月-2019年4月西南医科大学附属医院收治的155例肝硬化、42例肝硬化合并原发性肝癌（PHC）、150例慢性肝炎和73例健康体检者的临床资料。对所有研究对象均测定血清肝纤维化四项指标,比较各组间血清学指标的差异,并绘制受试者工作特征曲线（ROC曲线）比较肝纤维化四项的诊断效能。符合正态分布的计量资料2组间比较采用t检验,不符合正态分布的计量资料多组间比较采用Kruskal-Wallis H秩和检验,2组间进一步比较采用Wilcoxon秩和检验。计数资料组间比较采用χ2检验。结果肝硬化患者、肝硬化合并PHC患者血清肝纤维化四项指标的水平及阳性检出率均高于慢性肝炎患者和健康体检者（P值均<0. 05）,但肝硬化患者与肝硬化合并PHC患者PCⅢ、C-Ⅳ和HA水平及阳性检出率比较,差异均无统计学意义（P值均> 0. 05）。虽然肝硬化合并PHC患者的LN水平高于肝硬化患者（P <0...
- 肝硬化 /
- 诊断 /
- 对比研究
Abstract: Objective To investigate the value of the four serum liver fibrosis markers,i. e.,procollagen Ⅲ( PCⅢ),type Ⅳ collagen( C-Ⅳ),hyaluronic acid( HA),and laminin( LN),in the diagnosis of liver fibrosis. Methods A retrospective analysis was performed for the clinical data of 155 patients with liver cirrhosis,42 patients with liver cirrhosis and primary hepatic carcinoma( PHC),and 150 patients with chronic hepatitis who were admitted to The First Affiliated Hospital of Southwest Medical University from April 2018 to April2019,and 73 healthy individuals who underwent physical examination were also enrolled. The serum levels of the above four markers were measured for all subjects and were compared between groups. The receiver operating characteristic( ROC) curve was plotted to compare the diagnostic efficiency of these four markers. The t-test was used for normally distributed continuous data between two groups; the Kruskal-Wallis H rank sum test was used for comparison of non-normally distributed continuous data between multiple groups,and the Wilcoxon rank-sum test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between groups. Results The patients with liver cirrhosis and the patients with liver cirrhosis and PHC had significantly higher serum levels and positive rates of the four markers than the patients with chronic hepatitis and the healthy subjects( all P < 0. 05). while there were no significant differences in the levels and positive rates of PCⅢ,C-Ⅳ,and HA between the patients with liver cirrhosis and the patients with liver cirrhosis and PHC( all P > 0. 05). Although the patients with liver cirrhosis and PHC had a significantly higher serum level of LN than those with liver cirrhosis( P < 0. 05),there was no significant difference in the positive rate of LN between the two groups( P > 0. 05). The patients with alcoholic cirrhosis had significantly higher serum levels of PCⅢ and C-Ⅳ than those with viral cirrhosis,viral-alcoholic cirrhosis,or autoimmune cirrhosis( all P < 0. 05),the patients with autoimmune cirrhosis,alcoholic cirrhosis,or viral-alcoholic cirrhosis had a significantly higher serum level of HA than those with viral cirrhosis( all P < 0. 05),and the patients with viral-alcoholic cirrhosis,viral cirrhosis,or alcoholic cirrhosis had a significantly higher serum level of LN than those autoimmune( all P < 0. 05). The patients with chronic hepatitis of different etiologies had significantly lower serum levels and positive rates of these four markers than those with liver cirrhosis( all P < 0. 05),and the patients with severe viral hepatitis had significantly higher positive rates of the four markers than the other patients( all P < 0. 05). PC Ⅲ,C-IV,HA,LN,and the combination of these four markers had an area under the ROC curve of 0. 836,0. 832,0. 895,0. 808,and 0. 901,respectively,in the diagnosis of liver cirrhosis. HA had a significantly larger area under the ROC curve than PCⅢ,C-Ⅳ,and LN( all P < 0. 05),while there was no significant difference between HA and the combination of these four markers( P >0. 05). Conclusion HA has a high diagnostic efficiency in liver fibrosis.
- liver cirrhosis /
- diagnosis /
- comparative study

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参考文献(31)

[1] FRIEDMAN SL. Hepatic fibrosis-overview[J]. Toxicology,2008,254(3):120-129.

[2] LIN SR,QIAN JM,ZHOU LY,et al. Digestive internal medicine[M]. Beijing:People’s Military Medical Press,2013:377-381.(in Chinese)林三仁，钱家鸣，周丽雅，等．消化内科学[M]．北京:人民军医出版社，2013:377-381.

[3] PATELL K,BEDOSSA P,CASTERA L. Diagnosis of liver fibrosis:Present and future[J]. Liver Dis,2015,35(2):166-183.

[4] FOUAD SA,ESMAT S,OMRAN D,et al. Noninvasive assessment of hepatic fibrosis in Egyptian patients with chronic hepatitis C virus infection[J]. World J Gastroenterol,2012,18(23):2988-2994.

[5] EBRAHIMI H,NADERIAN M,SOHRABPOUR AA. New concepts on pathogenesis,diagnosis,and targeting of liver fibrosis; A review article[J]. Middle East J Did Dis,2016,8(3):166-178.

[6] KASWALA DH,LAI M,AFDHAL NH. Fibrosis assessment in nonalcoholic fatty liver disease(NAFLD)in 2016[J]. Dig Dis Sci,2016,61(5):1356-1364.

[7] VALKHOFF VE,STURKENBOOM MC,KUIPERS EJ. Risk factors for gastrointestinalbleeding associated with low-dose aspirin[J]. Best Pract Res Clin Gastroenterol,2012,26(2):125-140.

[8] GAMALl S,ALAA I,AHMED H,et al. Asian-Pacific Association for the Study of the Liver(APASL)consensus guidelines on invasive and non-invasive assessment of hepatic fibrosis:A 2016 update[J]. Hepatol Int,2017,11(1):1-30.

[9] FUKUI H,SAITO H,UENO Y,et al. Evidence-based clinical practice guidelines for liver cirrhosis 2015[J]. J Gastroenterol,2016,51(7):629-650.

[10] TERRAULT NA,LOK ASF,MCMAHON BJ,et al. Update on prevention,diagnosis,and treatment of chronic hepatitis B:AASLD 2018 hepatitis B guidance[J]. Hepatology,2018,67(4):1560-1599.

[11] National Health and Family Planning Comission of The People’s Republic of China. WS213-2018 Diagnosis for hepatitis C[J]. J Clin Hepatol,2018,34(8):1619-1621.(in Chinese)中华人民共和国国家卫生和计划生育委员会．WS213-2018丙型肝炎诊断[J]．临床肝胆病杂志，2018,34(8):1619-1621.

[12] National Workshop on Fatty 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 alcoholic liver disease:A 2018 update[J]. J Clin Hepatol,2018,34(5):939-946.(in Chinese)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，2018,34(5):939-946.

[13] CHEN HZ,ZHONG NS,LU ZY. Internal medicine[M]. 9th ed. Beijing:People’s Health Publishing House,2018:385-399.(in Chinese)陈灏珠，钟南山，陆再英．内科学[M]. 9版．北京:人民卫生出版社，2018:385-399.

[14] National Health and Family Planning Commission of the People’s Republic of China. Diagnosis,management,and treatment of hepatocellular carcinoma(V2017)[J]. J Clin Hepatol,2017,33(8):1419-1431.(in Chinese)中华人民共和国国家卫生和计划生育委员会．原发性肝癌诊疗规范(2017年版)[J]．临床肝胆病杂志，2017,33(8):1419-1431.

[15] Chinese Society of Hepatology,Chinese Medical Association;Chinese Society of Gastroenterology,Chinese Medical Association; Chinese Society of Infectious Diseases,Chinese Medical Association. Consensus on the diagnosis and management of autoimmune hepatitis(2015)[J]. J Clin Hepatol,2016,32(1):9-22.(in Chinese)中华医学会肝病学分会，中华医学会消化病学分会，中华医学会感染病学分会．自身免疫性肝炎诊断和治疗共识(2015)[J]．临床肝胆病杂志，2016,32(1):9-22.

[16] National Workshop on Fatty 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 Clin Hepatol,2018,34(5):947-957.(in Chinese)中华医学会肝病学分会脂肪肝和酒精性肝病学组．非酒精性脂肪肝肝病防治指南(2018更新版)[J]．临床肝胆病杂志，2018,34(5):947-957.

[17] LIU T,XU MY. Serologic diagnosis of liver fibrosis[J]. J Prac Hepatol,2016,19(1):1-4.(in Chinese)刘婷，徐铭益．肝纤维化的血清学诊断研究进展[J]．实用肝脏病杂志，2016,19(1):1-4.

[18] RODERFELD M,HEMMANN S,ROEB E. Mechanisms of fibrinolysis in chronic liver injury(with special emphasis on MMPs and TIMPs)[J]. Z Gastroenterol,2007,45(1):25-33.

[19] MAHMOUD AA,BAKIR AS,SHABANA SS. Serum TGF-β，Serum MMP-1,and HOMA-IR as non-invasive predictors of fibrosis in Egyptian patients with NAFLD[J]. Saudi J Gastroenterol,2012,18(5):327-333.

[20] SAITOU Y,SHIRAKI K,YAMANAKA Y. Noninvasive estimation of liver fibrosis and response to interferon therapy by a serum fibrogenesis marker,YKL-40,in patients with HCV-associated liver disease[J]. World J Gastroenterol,2005,11(4):476-481.

[21] AHMED S,ABEDEL H,LAILA N,et al. Role of fibroscan,TGF-β1,and YKL-40 in the detection of hepatic fibrosis in chronic hepatitis C patients with and without schistosomiasis[J]. Egypt Liver J,2015,5(3):47-53.

[22] ZHANG HY,ZHANG Y,WANG XH,et al. Value of IGFBPr P1and contrast-enhanced ultrasound in liver fibrosis staging with rabbits[J]. Int J Clin Exp Med,2017,10(8):11606-11615.

[23] UMEMURA T,JOSHITA S,SEKIGUCHI T,et al. Serum wisteria floribunda agglutinin-positive mac-2-binding protein level predicts liver fibrosis and prognosis in primary biliary cirrhosis[J]. Am J Gastroenterol,2015,110(6):857-864.

[24] LIU LX,LYU TT. A challenge of serological diagnosis in liver fibrosis[J/CD]. Chin J Digest Med Imageol:Electronic Edition,2018,8(1):1-6.(in Chinese)刘立新，吕婷婷．肝纤维化血清学诊断标记物[J/CD]．中华消化病与影像杂志:电子版，2018,8(1):1-6.

[25] LIN YM,WANG YL,HE M,et,al. Clinical significance of combined determination of liver fibrosis indexes from liver disease patients’serum[J]. Chongqing Med,2014,43(29):3921-3922.(in Chinese)林一民，王云龙，何萌，等．肝病患者血清肝纤维化指标联合测定的临床意义[J]．重庆医学，2014,43(29):3921-3922.

[26] SORESI M,GIANNITRAPANI L,CERVELLO M,et al. Non invasive tools for the diagnosis of liver cirrhosis[J]. World J Gastroenterol,2014,20(48):18131-18150.

[27] DONG FC,LONG JL,LIN LQ,et al. The value of serum fibrosis indexes combined with liver function tests in the evaluation of hepatic fibrosis in patients with hepatitis B[J]. J Shenyang Med Coll,2018,20(3):224-226.(in Chinese)董福昌，龙健灵，林丽卿，等．血清肝纤维化指标联合肝生化检测对乙肝患者肝纤维化的评估[J]．沈阳医学院学报，2018,20(3):224-226.

[28] MAZZARA S,SINISI A,CARDACI A,et al. Two of them do it better:Novel serum biomarkers improve autoimmune hepatitis diagnosis[J]. PLo S One,2015,10(9):e0137927.

[29] GRESSNER AM,RIZK M,GAO CF,et al. Potential novel biomarkers for monitoring the fibrogenic process in liver[J]. Arab J Gastroenterol,2010,10(4):s12-s16.

[30] DU W,SHAN YL,LIAO QL,et,al. Clinical significances of HA,PⅢNP,LN and CⅣin the diagnosis of chronic liver disease and liver fibrosis[J]. J Chongqing Med Univ,2013,38(5):530-533.(in Chinese)杜伟，单幼兰，廖权利，等．HA、PⅢNP、LN、CⅣ在慢性肝病及肝纤维化诊断中的临床意义[J]．重庆医科大学学报，2013,38(5):530-533.

[31] CALES P,OBERTI F,MIEHAIAK S,et al. A novel panel of blood markers to assess the degree of liver fibrosis[J]. Hepatology,2005,42(6):1373-1381.

施引文献

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