Clinical value of Golgi protein 73 and hyaluronic acid in diagnosis of the progression of hepatitis B virus-related chronic liver diseases
-
摘要: 目的探讨高尔基体蛋白73(GP73)与透明质酸(HA)在HBV相关慢性肝病进展中的临床应用价值。方法收集2016年12月-2017年4月就诊于青岛大学附属医院的患者142例,其中伴有肝硬化的肝细胞癌(HCC)36例(HCC组),乙型肝炎肝硬化66例(肝硬化组),慢性乙型肝炎(CHB)40例(CHB组)。另选取同一时期健康体检者30例作为对照。ELISA法检测血清中GP73浓度,化学发光法检测HA浓度。正态分布的计量资料多组间比较单因素方差分析;非正态分布的计量资料多组间比较采用Kruskal-Wallis H检验,进一步两两比较采用Mann-Whitney U检验。曲线分析比较GP73和HA单独或联合应用的临床诊断价值。受试者工作特征曲线下面积(AUC)比较采用Z检验,性别比、敏感度及特异度比较采用χ2检验。结果 CHB组、肝硬化组及HCC组患者血清GP73和HA水平均高于对照组(P值均<0.05)。肝硬化组、HCC组患者GP73和HA水平均明显高于CHB组(U值分别为677、637、291、193,P值均<0.05)。肝硬化组内比较,失代偿期患者GP...Abstract: Objective To investigate the clinical value of Golgi protein 73 ( GP73) and hyaluronic acid ( HA) in the diagnosis of the progression of hepatitis B virus ( HBV) -related chronic liver diseases. Methods A total of 142 patients who visited The Affiliated Hospital of Qingdao University from December 2016 to April 2017 were enrolled, and among these patients, 36 had hepatocellular carcinoma ( HCC) with liver cirrhosis, 66 had hepatitis B cirrhosis, and 40 had chronic hepatitis B ( CHB) . A total of 30 healthy subjects who underwent physical examination during the same period of time were enrolled as control group. ELISA was used to measure the serum level of GP73, and chemiluminescence was used to measure the level of HA. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Mann-Whitney U test was used for further comparison between any two groups. The receiver operating characteristic ( ROC) curve was used to analyze the diagnostic value of GP73 and HA measured alone or in combination. The Z test was used for comparison of area under the ROC curve ( AUC) , and the chi-square test was used for comparison of sex ratio, sensitivity, and specificity. Results The CHB group, liver cirrhosis group, and HCC group had significantly higher serum levels of GP73 and HA than the control group ( all P < 0. 05) . The liver cirrhosis group and the HCC group had significantly higher serum levels of GP73 and HA than the CHB group ( U = 677, 637, 291, and 193, all P < 0. 05) . In the liver cirrhosis group, the patients with decompensated liver cirrhosis had significantly higher serum levels of GP73 and HA than those with compensated liver cirrhosis ( U = 171 and 212, both P < 0. 05) . As for CHB patients, combined measurement of GP73 and HA had significantly higher AUC and sensitivity than GP73 measured alone ( AUC: 0. 950 vs 0. 790, Z = 2. 32, P < 0. 05; sensitivity: 91. 70% vs 72. 20% , χ2= 5. 14, P < 0. 05) . In the diagnosis of liver cirrhosis, GP73 had a significantly higher sensitivity than HA ( 87. 90% vs 69. 70% , χ2= 6. 05, P < 0. 05) , and compared with HA measured alone, combined measurement of GP73 and HA had a significant reduction in specificity ( 62. 30% vs 86. 80% , χ2= 14. 60, P < 0. 05) and a significant increase in sensitivity ( 93. 90% vs 69. 70% , χ2= 11. 80, P < 0. 05) . In the diagnosis of decompensated liver cirrhosis, combined measurement of GP73 and HA a significantly higher sensitivity than HA measured alone ( 83. 80% vs 67. 60% , χ2= 4. 17, P < 0. 05) . GP73, HA, and alpha-fetoprotein ( AFP) had an AUC of 0. 549, 0. 525, and 0. 807, respectively, in the diagnosis of HCC, and GP73 and HA had a lower diagnostic value than AFP ( Z = 3. 49 and 3. 80, both P < 0. 05) . Conclusion GP73 and HA can help with the monitoring of the progression of HBV-related chronic liver diseases. Combined measurement of GP73 and HA has an important clinical value in the diagnosis of liver cirrhosis and decompensated liver cirrhosis.
-
Key words:
- Golgi protein 73 /
- hyaluronic acid /
- hepatitis B, chronic /
- liver cirrhosis /
- carcinoma, hepatocellular /
- diagnosis
-
[1]Mc MAHON BJ.Epidemiology and natural history of hepatitis B[J].Semin Liver Dis, 2005, 25 (Suppl 1) :3-8. [2]YANG JD, KIM WR, COELHO R, et al.Cirrhosis is present in most patients with hepatitis B and hepatocellular carcinoma[J].Clin Gastroenterol Hepatol, 2011, 9 (1) :64-70. [3]MARRERO JA, ROMANO PR, NIKOLAEVA O, et al.GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma[J].J Hepatol, 2005, 43 (6) :1007-1012. [4]LE P, GAO GS, DONG FB, et al.Serum Golgi protein 73 and three noninvasive serum score systems for diagnosis of liver fibrosis in patients with chronic hepatitis B[J].Chin J Nosocomiol, 2016, 26 (11) :2529-2531, 2543. (in Chinese) 乐萍, 高国生, 董飞波, 等.血清高尔基体蛋白73及3种评分系统对慢性乙型肝炎患者肝纤维化的预测价值研究[J].中华医院感染学杂志, 2016, 26 (11) :2529-2531, 2543. [5]XU Z, LIU L, PAN X, et al.Serum Golgi protein 73 (GP73) is a diagnostic and prognostic marker of chronic HBV liver disease[J].Medicine (Baltimore) , 2015, 94 (12) :e659. [6]WU JW, WANG W, LIN SR.Change of hyaluronan and hyaluronan associated proteins in the development of chronic liver diseases and its significance[J].Lab Med Clin, 2013, 10 (7) :777-779. (in Chinese) 吴吉文, 王玮, 林寿榕.透明质酸及其相关蛋白在慢性肝病病程进展中的变化[J].检验医学与临床, 2013, 10 (7) :777-779. [7]HUANG LG, REN Z, REN L, et al.Clinical value of combined detection of four serum indicators in chronic liver disease patients[J].Int J Lab Med, 2013, 34 (2) :167-168. (in Chinese) 黄连贵, 任重, 任力, 等.慢性肝病患者血清四项指标联合检测的临床价值[J].国际检验医学杂志, 2013, 34 (2) :167-168. [8] 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. [9]Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association.The guideline of prevention and treatment for chronic hepatitis B:a 2015 update[J].J Clin Hepatol, 2015, 31 (12) :1941-1960. (in Chinese) 中华医学会肝病学分会, 中华医学会感染病学分会.慢性乙型肝炎防治指南 (2015年更新版) [J].临床肝胆病杂志, 2015, 31 (12) :1941-1960. [10]CHEN Y, WANG BE, JIA JD, et al.Noninvasive evaluation of liver fibrosis in chronic hepatitis B patients[J].Chin J Hepatol, 2003, 11 (6) :354-357. (in Chinese) 陈煜, 王宝恩, 贾继东, 等.慢性乙型肝炎肝纤维化程度的无创性评估[J].中华肝脏病杂志, 2003, 11 (6) :354-357. [11]KLADNEY RD, BULLA GA, GUO L, et al.GP73, a novel Golgi-localized protein upregulated by viral infection[J].Gene, 249 (1-2) :53-65. [12]ZHANG XM, WEI MJ, XU ZJ, et al.Pattern of serumα-fetal protein, intereleukin-6 and Golgi protein 73 expressed in liver diseases and their diagnostic value on hepatocellular carcinoma[J/CD].Chin J Exp Clin Infect Dis:Electronic Version, 2017, 11 (4) :339-344. (in Chinese) 张小曼, 魏梅娟, 许正锯, 等.血清甲胎蛋白、白细胞介素-6和高尔基体蛋白73在肝脏疾病中的表达特点及其对肝细胞癌的诊断价值[J/CD].中华实验和临床感染病杂志:电子版, 2017, 11 (4) :339-344. [13]LIU T, YAO M, LIU S, et al.Serum Golgi protein 73 is not a suitable diagnostic marker for hepatocellular carcinoma[J].Oncotarget, 2017, 8 (10) :16498-16506. [14]WEI H, LI B, ZHANG R, et al.Serum GP73, a marker for evaluating progression in patients with chronic HBV infections[J].PLo S One, 2013, 8 (2) :e53862. [15]SUZUKI A, ANGULO P, LYMP J, et al.Hyaluronic acid, an accurate serum marker for severe hepatic fibrosis in patients with non-alcoholic fatty liver disease[J].Liver Int, 2005, 25 (4) :779-786. [16]ZHANG XD, LI WJ, GAO YN, et al.Diagnosis value of serum laminin and hyaluronic acid in liver fibrosis[J].China Med Herald, 2017, 14 (23) :111-113, 121. (in Chinese) 张新弟, 李卫娟, 高娅妮, 等.血清层粘连蛋白、透明质酸诊断肝纤维化的价值[J].中国医药导报, 2017, 14 (23) :111-113, 121. [17]YAO JY, ZHONG BH, CHAO K, et al.Serological diagnosis of liver fibrosis[J].Chin J Gastroenterol Hepatol, 2011, 20 (8) :687-691. (in Chinese) 姚佳燕, 钟碧慧, 晁康, 等.肝纤维化血清学诊断的研究[J].胃肠病学和肝病学杂志, 2011, 20 (8) :687-691. [18]TAN QW, GUO W, ZHANG CY, et al.Value of Golgi protein 73 (GP73) for diagnosis and grading of liver cirrhosis[J].J Diagn Concepts Pract, 2013, 12 (5) :516-521. (in Chinese) 谈绮文, 郭玮, 张春燕, 等.血清高尔基体蛋白73在肝硬化诊断及分级中的价值[J].诊断学理论与实践, 2013, 12 (5) :516-521. [19]ZHANG WZ, TAO CH, LI Y.The changes and clinical value of serum Golgi protein 73 level in chronic HBV patient[J].Lab Med Clin, 2016, 13 (23) :3325-3328. (in Chinese) 张文昭, 陶才华, 李莹.乙肝患者血清高尔基蛋白73水平改变及其临床意义[J].检验医学与临床, 2016, 13 (23) :3325-3328. [20]WANG CM, SUN L, ZHANG BW.Clinical profile and characteristics of serum GP73 in cirrhotic patients with chronic hepatitis B infections[J].Int J Lab Med, 2016, 37 (6) :765-766. (in Chinese) 王纯明, 孙莉, 张宝伟.乙型肝炎合并肝硬化患者血清GP73变化特征及临床意义[J].国际检验医学杂志, 2016, 37 (6) :765-766. [21]LU FM.Serological diagnosis of hepatocellular carcinoma:challenges and opportunities[J].J Clin Hepatol, 2017, 33 (7) :1262-1265. (in Chinese) 鲁凤民.肝细胞癌的血清学诊断——挑战与希望同在[J].临床肝胆病杂志, 2017, 33 (7) :1262-1265. 期刊类型引用(25)
1. 陈炜. 终末期肝病模型联合血清钠评分对肝衰竭患者短期预后的预测价值. 川北医学院学报. 2024(02): 247-251 . 百度学术
2. 王学英. MELD-Na评分联合NLR预测肝硬化食管胃静脉曲张破裂出血后再出血的临床价值. 罕少疾病杂志. 2024(05): 70-72 . 百度学术
3. 林小洪,吴文楠,荀振. 血小板-白蛋白-胆红素评分与肝硬化患者肝功能Child-Turcotte-Pugh分级的相关性分析. 福建医科大学学报. 2024(01): 37-43 . 百度学术
4. 孙玉,秦维,王丹,郑艳丽,霍玉玲. 前白蛋白及纤维蛋白原水平与代偿期肝硬化食管静脉曲张发生的关系. 中国肝脏病杂志(电子版). 2024(02): 7-12 . 百度学术
5. 石红. 延续性护理服务方案对肝硬化食管胃静脉曲张内镜下精准断流术后的临床影响研究. 基层医学论坛. 2024(20): 114-116+142 . 百度学术
6. 李欣忆,李娇娇,孙蔚. 肝硬化食管胃底静脉曲张破裂出血患者经颈静脉肝内门体分流术后发生显性肝性脑病的列线图预测模型建立及评价. 临床肝胆病杂志. 2024(08): 1605-1611 . 本站查看
7. 杨丹,周健. 多种无创预测模型在肝硬化门静脉高压中的研究进展. 中国临床研究. 2024(11): 1778-1783 . 百度学术
8. 陈刚,谷光丽,何映雪,唐尧. 血清表皮生长因子对肝硬化食管胃静脉曲张患者再出血的诊断价值分析. 转化医学杂志. 2024(10): 1698-1702 . 百度学术
9. 喻雪珂,黎孟玲,彭思远,申月明,梁纶熙,曾亚. 食管胃底静脉曲张破裂出血对肝硬化患者1年死亡结局的影响及相关因素研究. 中国全科医学. 2023(14): 1745-1752 . 百度学术
10. 郝艳萍,韩靓,仇晶辉,滕圣智,王建华. 乙肝肝硬化食管胃静脉曲张急性出血患者内镜下治疗后发生菌血症的危险因素分析. 中国消毒学杂志. 2023(03): 182-184 . 百度学术
11. 顾达,童聪,赵祥安,向晓星. PC/SD、FIB-4指数、CTP评分、MELD评分、MELD-Na评分在预测肝硬化食管静脉曲张出血套扎术后1年内再出血的价值评估. 胃肠病学和肝病学杂志. 2023(03): 289-294 . 百度学术
12. 朱会明,张华,张金荣,吴雪华,吴柳,刘义安. 肝硬化血瘀证患者食管胃底静脉曲张相关性研究. 中国中医急症. 2023(04): 665-668 . 百度学术
13. 周苏云,周影,程新月. 肝硬化患者发生肝性脑病的影响因素分析及对预检分诊意义的探讨. 中西医结合护理(中英文). 2023(03): 130-132 . 百度学术
14. 葛琴. 血府逐瘀汤联合双歧杆菌三联活菌治疗酒精性肝硬化的疗效研究. 中医临床研究. 2023(20): 142-145 . 百度学术
15. 邱荣金,卢劲瑜,苏雪梅,郑凤祥,廖丽芳. 预防使用抗生素对食管胃静脉曲张内镜下治疗的影响评估. 中国现代药物应用. 2023(19): 99-101 . 百度学术
16. 邢恩涛,赵孟杰,金鹏飞,武振东,刘志春. 肝硬化门静脉高压TIPS术后HVPG下降相关因素. 青岛大学学报(医学版). 2023(05): 759-762 . 百度学术
17. 刘媛,徐建光,何雪云,万秀萍,林小花,王莉娟,郑临海. 血钙浓度联合MELD评分对肝硬化严重程度的预测价值. 浙江中西医结合杂志. 2022(02): 129-130+149 . 百度学术
18. 张春燕,田正方,朱经科,晁燕茹. 肝硬化患者食管静脉曲张套扎术后再出血影响因素分析及干预对策. 黑龙江医药科学. 2022(02): 96-99 . 百度学术
19. 俞斌,屠军,沈玉玲. AIMS65评分预测肝硬化食管胃底静脉曲张破裂出血患者死亡的价值. 胃肠病学和肝病学杂志. 2022(07): 737-742 . 百度学术
20. 刘益,周自忠,刘刚,徐海荣. 食管胃底静脉曲张破裂出血患者急诊TIPS术后肝性脑病发生特征及危险因素分析. 肝脏. 2022(06): 658-661 . 百度学术
21. 廖翔. 肝硬化患者SAAG与食管胃底静脉曲张破裂出血的关系研究. 现代诊断与治疗. 2022(11): 1646-1648+1692 . 百度学术
22. 张春燕,田正方,朱经科,晁燕茹. 肝硬化患者食管静脉曲张套扎术后再出血影响因素分析. 黑龙江医药科学. 2022(05): 171-173 . 百度学术
23. 曾伍姣,张知洪,陈令民,李亦明. 血管紧张素Ⅱ水平在肝硬化患者诊断中的应用及与MELD评分关系研究. 肝胆外科杂志. 2021(01): 60-63 . 百度学术
24. 祝强,杨继敏,刘中亮. 八种评分系统对肝硬化失代偿期患者短期预后的预测价值. 中国医药科学. 2021(19): 18-22 . 百度学术
25. 赵媛,赵明,范玉梅,邵建营. 失代偿期乙型肝炎肝硬化患者不同病毒学应答状态对生存率及肝癌患病率的影响. 中国实用医刊. 2020(23): 50-52 . 百度学术
其他类型引用(9)
-