Clinical value of Golgi protein 73 and hyaluronic acid in diagnosis of the progression of hepatitis B virus-related chronic liver diseases

Zhang LiJun; Liu MingJun; Wang Shuai; Wang Lin; Wang RuKun; Hou HuaBin; Sun GuiRong; Zhang NaNa; Liu LinJie

doi:10.3969/j.issn.1001-5256.2018.01.013

Issue 1

Jan. 2018

Turn off MathJax

Article Contents

Abstract

References

Article Navigation > Journal of Clinical Hepatology > 2018 > 34(1): 63-67

PDF( 1658 KB)

Clinical value of Golgi protein 73 and hyaluronic acid in diagnosis of the progression of hepatitis B virus-related chronic liver diseases

DOI: 10.3969/j.issn.1001-5256.2018.01.013

Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China

Published Date: 2018-01-20

Abstract

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.
- Golgi protein 73,
- hyaluronic acid,
- hepatitis B, chronic,
- liver cirrhosis,
- carcinoma, hepatocellular,
- diagnosis

FullText(HTML)

References(21)

References

[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.

Relative Articles

[1]	Tong LIU, Shanzheng LI, Cheng ZHOU, Sutong LIU, Lihui ZHANG, Wenxia ZHAO. Study on the protective efect and mechanism of paeoniflorin on palmitic acid-induced HepG2 cells[J]. Journal of Clinical Hepatology, 2025, 41(3): 499-505. doi: 10.12449/JCH250316
[2]	Lai Xin, Zhou TaiCheng, Wei Jia. Association between HBV A1762T/G1764A double nucleotide substitution and liver diseases[J]. Journal of Clinical Hepatology, 2018, 34(9): 1990-1994. doi: 10.3969/j.issn.1001-5256.2018.09.034
[3]	Pang Ting, Xing HuiChun. Correlation between drug-resistance gene mutations and hepatocellular carcinoma in patients with hepatitis B virus infection[J]. Journal of Clinical Hepatology, 2017, 33(1): 82-86. doi: 10.3969/j.issn.1001-5256.2017.01.017
[4]	Du SenRong, Mao XiaoRong, Xiao Ping, Chen Hong. Effects of PARP-1 inhibitors AG-014699 and AZD2281 on proliferation and apoptosis of human hepatoma cell line HepG2[J]. Journal of Clinical Hepatology, 2015, 31(6): 943-946. doi: 10.3969/j.issn.1001-5256.2015.06.027
[5]	Wang LiPing, Han FangZheng, Li ChunYang, Yan Mei, Zhang YanChao, Yan XueBing. Evaluation of adefovir primary resistance and adefovir repulsive mutations of the HBV DNA P gene in chronic hepatitis B patients[J]. Journal of Clinical Hepatology, 2012, 28(8): 606-608.
[6]	Jin WenWen, Xin YongNing, Dong QuanJiang, Zhao ShouFeng, Yu XinJuan, Jiang Man, Xu Jing, Xuan ShiYing. The preliminary study on the relationship between hepatitis B virus BCP gene mutations and HBV-related primary hepatocellular carcinoma in Qingdao[J]. Journal of Clinical Hepatology, 2012, 28(2): 130-134.
[7]	Yang YanLin, Xiao Ping, Gao Peng, Wang LiMing, Wei XiSheng, He Qiang, Zhou Ping. Distribution of HBV genotypes and YMDD mutations in E antigen-positive patients[J]. Journal of Clinical Hepatology, 2012, 28(6): 428-430.
[8]	Hong YuBo, Zhang Ting, Sun LiGuang. Association between IL-2 +114 (G/T) polymorphism and susceptibility to hepatitis B, cirrhosis, and hepatocellular carcinoma in Jilin province[J]. Journal of Clinical Hepatology, 2012, 28(12): 930-933.
[9]	Deng Le, Wen ZhiLi. Review of recent research progress in correlating HBV genotypes with efficacy of antiviral treatments[J]. Journal of Clinical Hepatology, 2012, 28(6): 469-473.
[10]	Zhang JianJun, Wu LiPing, Du RuiQing, Wang JianBin, Yao ZhanCheng, Yu GuiQin. Factors correlating with the liver inflammation grade ≥G2 in chronic HBV-infected patients with normal liver function[J]. Journal of Clinical Hepatology, 2012, 28(1): 35-38.
[11]	Liu JinPing, Liu YouDe, Guo YanMei, Yang ShaoPing, Lin Qing, Lin Ling. Clinical characteristics and distribution of hepatitis B virus genotypes in CHB patients in Yantai area[J]. Journal of Clinical Hepatology, 2011, 27(12): 1288-1290.
[12]	Zou XiaoJing, Jiang XueQiang, Tian DeYing. Role of DC-SIGN on the maturation and activation of dendritic cells in chronic hepatitis B virus infection[J]. Journal of Clinical Hepatology, 2011, 27(2): 145-147+153.
[13]	Xiong QiXiang, Xiong LiJuan. Hepatitis B virus infection and DNA methylation in hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2011, 27(8): 881-884.
[14]	Pan Lei, Wei Xin, Xie YuMei, Hao ChunQiu, Wang JiuPing, Jia ZhanSheng, Bai XueFan. Anti-viral therapy with pegylated interferon alpha-2a plus ribavirin in patients co-infected with HBV and HCV[J]. Journal of Clinical Hepatology, 2011, 27(1): 84-85+95.
[15]	Yuan JianGuo, Wang XinGuo, Cui Xia, Liu FengHua, Wang FengHua, Song JiKui, Zhao HongKui. The activation of rat hepatic stellate cells stimulated with hepatitis B virus in vitro[J]. Journal of Clinical Hepatology, 2011, 27(2): 163-165.
[16]	Xi HongLi, Liu FangFang, Yuan JiaYing, Yu YanYan. Significance and detection of IL-2、IL-4 and IFN-γ in PBMC from patients with hepatitis B virus infection[J]. Journal of Clinical Hepatology, 2010, 26(6): 627-629.
[17]	Wang GuoQiang, Niu JuXia. The HBx protein mutation among different HBV genotypes[J]. Journal of Clinical Hepatology, 2010, 26(4): 392-394.
[18]	Shi YanMei, Lan YingHua, Dan Lei, Zhou Jin, Li YongGuo. The relationship between of hematopoietic stem cells and hepatitis B virus infection[J]. Journal of Clinical Hepatology, 2010, 26(4): 377-380.
[19]	Xie DeSheng, Zhang QingBo, Chen ChangXing, Huang JianFang, Ma Jin, Huang HaiBin, Du Yao. The relationship between HBV gene mutation in HBV infected family and HLA class Ⅱ alleles[J]. Journal of Clinical Hepatology, 2010, 26(4): 383-386.
[20]	Xu ZhengJu, Yang Hong, Zhang QiHua, Chen XianLi, Li ShuQing, Wang ChongGuo. Study on the relationship between hepatitis B virus genotypes and effect of lamivudine therapy.[J]. Journal of Clinical Hepatology, 2005, 21(3): 157-159.

Supplements(0)

Cited By

Cited by

Periodical cited type(2)

1.	中国抗癌协会肿瘤消融治疗专业委员会，中国临床肿瘤学会肿瘤消融治疗专家委员会，中国医师协会介入医师分会介入围手术学组. 复合式冷热消融治疗肝肿瘤围手术期管理专家共识. 中华内科杂志. 2025(02): 110-118 .
2.	温钊，臧铁柱，宋晓改，张炫，江艳丽. 射频消融治疗包膜下与非包膜下早期肝细胞癌患者的远期预后. 河南医学研究. 2023(15): 2738-2744 .

Other cited types(0)

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Get Citation

PDF

XML

Article Metrics

Article views (2709) PDF downloads(507)

Clinical value of Golgi protein 73 and hyaluronic acid in diagnosis of the progression of hepatitis B virus-related chronic liver diseases

DOI: 10.3969/j.issn.1001-5256.2018.01.013