血浆GP73联合肝脏硬度检测诊断乙型和丙型肝炎患者肝纤维化临床价值分析*

doi:10.3969/j.issn.1672-5069.2020.06.013

摘要/Abstract

摘要： 目的探讨血浆高尔基体蛋白73(GP73)水平联合肝脏硬度测定(LSM)诊断慢性乙型和丙型肝炎患者肝纤维化分期的价值。方法 2015年6月～2019年1月我院收治的慢性乙型肝炎患者46例,慢性丙型肝炎患者98例,乙型肝炎肝硬化患者17例,丙型肝炎肝硬化患者35例,另选择健康人56例,使用Fibrotouch检测LSM,采用ELISA法检测血浆GP73水平。对肝病患者行肝活检。应用受试者工作特征曲线(ROC)分析GP73、LSM及两者联合诊断肝纤维化的效能。结果在本组196例患者中,经病理学检查,诊断为S₁期45例(23.0%),S₂期50例(25.5%),S₃期49例(25.0%)和S₄期52例(26.5%),其中≥S₂期者151例(77.0%),≥S₃期者101例(51.5%); S₁、S₂、S₃和S₄期患者血浆GP73水平分别为(118.1±30.6) ng/ml、(135.8±39.7) ng/ml、(175.8±54.8) ng/ml和(228.7±74.6)ng/ml,LSM分别为(6.1±1.8) kpa、(10.1±2.2) kpa、(15.3±4.5) kpa和(23.0±9.4) kpa,均显著高于健康人[分别为为(94.0±19.4) ng/ml和(5.4±2.0 )kpa,P＜0.05];ROC曲线分析显示,GP73诊断肝纤维化≥S₂、≥S₃和S₄的截断点分别为127.7 ng/ml、142.5 ng/ml和155.6 ng/ml,LSM诊断的截断点分别为8.8 kPa、12.6 kPa和17.9 kPa,两者联合诊断的ROC下面积(AUC)分别为0.917(95% CI:0.875～0.948)、0.954(95% CI:0.920～0.977)和0.950(95% CI:0.914～0.973),其灵敏度分别为71.5%、86.1%和88.5%,其特异度分别为94.6%、95.1%和89.1%,准确性分别为96.8%、92.3%和90.7%。结论应用血浆GP73联合LSM诊断乙型和丙型肝炎患者肝纤维化的效能较好,值得临床进一步验证。

关键词: 乙型肝炎, 丙型肝炎, 肝纤维化, 肝脏硬度检测, 高尔基体蛋白73, 诊断试验

Abstract: Objective The aim of this study was to explore the diagnostic diagnostic values of plasma Golgi protein 73 (GP73) and liver stiffness measurement (LSM) combination for liver fibrosis in patients with hepatitis B and C. Methods 46 patients with hepatitis B, 98 patients with hepatitis C, 17 patients with hepatitis B liver cirrhosis and 35 patients with hepatitis B liver cirrhosis as well as 56 healthy persons were enrolled in our hospital between June 2015 and January 2019, and plasma GP73 levels were detected by ELISA and LSM was obtained by Fibrotouch. Liver biopsies were performed in all the patients. The diagnostic efficacy was evaluated by area under ROC. Results Out of our series, the histopathological examination showed that liver fibrosis staging (S)1 in 45 (23.0%), S₂ in 50 (25.5%), S₃ in 49 (25.0%) and S₄ in 52 patients(26.5%), with ≥S₂ in 151 (77.0%) and ≥S₃ in 101 (51.5%); plasma GP73 levels in patients with S₁, S₂, S₃ and S₄ were (118.1±30.6) ng/ml, (135.8±39.7) ng/ml, (175.8±54.8) ng/ml and (228.7±74.6)ng/ml, and LSM were (6.1±1.8) kpa, (10.1±2.2) kpa, (15.3±4.5) kpa and (23.0±9.4) kpa, respectively, all significantly higher than (94.0±19.4) ng/ml and (5.4±2.0 ) kpa (P＜0.05) in healthy persons; the cut-off-value of plasma GP73 in diagnosing liver fibrosis ≥S₂, ≥S₃ and equal to S₄ were 127.7 ng/ml, 142.5 ng/ml and 155.6 ng/ml, and that of LSM were 8.8 kPa, 12.6 kPa and 17.9 kPa, and the diagnostic area under ROC of the two combination were 0.917(95% CI:0.875-0.948), 0.954(95% CI:0.920-0.977) and 0.950(95% CI:0.914-0.973), with the sensitivity of 71.5%, 86.1% and 88.5%, the specificity of 94.6%, 95.1% and 89.1%, and accuracy of 96.8%, 92.3% and 90.7%, respectively. Conclusion The application of plasma GP73 level and LSM combination in predicting liver fibrosis in patients with chronic hepatitis B and hepatitis C is feasible and simple, which warrants further investigation.

Key words: Hepatitis B, Hepatitis C, Liver fibrosis, Golgi protein 73, Liver stiffness measurement, Diagnostic trial

崔璐瑶, 苑喜微, 刘领弟, 张莹, 赵文, 赵丹丹, 杨杨, 南月敏. 血浆GP73联合肝脏硬度检测诊断乙型和丙型肝炎患者肝纤维化临床价值分析^*[J]. 实用肝脏病杂志, 2020, 23(6): 809-812.

Cui Luyao, Yuan Xiwei, Liu Lingdi, et al. Diagnostic values of plasma Golgi protein 73 and liver stiffness measurement combination for liver fibrosis in patients with hepatitis B and C[J]. Journal of Practical Hepatology, 2020, 23(6): 809-812.

参考文献

[1] D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol,2006,44(1):217-231.
[2] Cardoso AC,Carvalho-Filho RJ, Marcellin P. Transient elastography in chronic viral hepatitis:a critical appraisal. Gut,2011,60(6):759-764.
[3] Ferraioli G,Tinelli C,Dal-Bello B,et al. Performance of liver stiffness measurements by transient elastography in chronic hepatitis. World J Gastroenterol,2013,19(1):49-56.
[4] Stebbing J,Farouk L,Panos G,et al. A meta-analysis of transient elastography for the detection of hepatic fibrosis. J Clin Gastroenterol,2010,44(3):214-219.
[5] 袁平戈.瞬时弹性成像技术在肝病诊断中的应用进展.实用肝脏病杂志,2016, 19(1): 4-7.
[6] Anca T,Catalin S,Camelia C,et al. Increased liver stiffness in extra-hepatic cholestasis caused by choledocholithiasis. Hepat Mon,2011,2011(5):372-375.
[7] Castéra L,Foucher J,Bernard PH,et al. Pitfalls of liver stiffness measurement:a 5-year prospective study of 13,369 examinations. Hepatology,2010,51(3):828-835.
[8] Weiskirchen R,Tacke F. Combining Golgi protein 73 with liver stiffness measurements:a proof-of-concept for non-invasive fibrosis assessment in antiviral-naive HBV patients. Liver Int,2017,37(11):1605.
[9] Iftikhar R,Kladney RD,Havlioglu N,et al. Disease-and cell-specific expression of Golgi protein 73 in human liver disease. AM J Gastroenterol,2004,99:1087-1095.
[10] 中华医学会肝病学分会及感染病学分会.慢性乙型肝炎防治指南(2015更新版).实用肝脏病杂志,2016,19(3):Ⅴ-ⅩⅩⅢ.
[11] 中华医学会肝病学分会及感染病学分会.丙型肝炎防治指南(2015年更新版).实用肝脏病杂志,2015,29(12):1961-1979.
[12] 中国肝炎防治基金会,中华医学会感染病学分会,中华医学会肝病学分会和中国研究型医院学会肝病专业委员会.瞬时弹性成像技术诊断肝纤维化专家共识(2018年更新版).中华肝脏病杂志,2019,27(3):182-191.
[13] Bedossa P,Poynard T. An algorithm for the grading of activity in chronic hepatitis C. Hepatology,1996,24(2):289-293.
[14] 中华医学会肝病学分会、消化病学分会及感染病学分会.肝纤维化诊断及治疗共识(2019年).实用肝脏病杂志,2019,22(6):793-803.
[15] Campana L,Iredale JP. Regression of liver fibrosis. Semin Liver Dis,2017,37(1):1-10.
[16] Marcellin P,Gane E,Buti M,et al.Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B:a 5-year open-label follow-up study. Lancet,2013,381(9865):468-475.
[17] Cadranel JF,Rufat P,Degos F. Practices of liver biopsy in France:results of a prospective nationwide survey. Hepatology,2000,32:477-481.
[18] Tseng PL,Wang JH,Hung CH,et al. Comparisons of noninvasive indices based on daily practice parameters for predicting liver cirrhosis in chronic hepatitis B and hepatitis C patients in hospital and community populations. Kaohsiung J Med Sci,2013,29(7):385-395.
[19] Lim JK,Flamm SL,Singh S,et al. American gastroenterological association institute guideline on the role of elastography in the evaluation of liver fibrosis. Gastroenterology,2017,152(6):1536-1543.
[20] Bellan M,Castello LM,Pirisi M. Candidate biomarkers of liver fibrosis:a concise,pathophysiology-oriented review. J Clin Transl Hepatol,2018,6(3):317-325.
[21] Kladney RD,Bulla GA,Guo L,et al. GP73,a novel Golgi-localized protein upregulated by viral infection. Gene,2000,249(1):53-65.
[22] Mao Y,Yang H,Xu H,et al. Golgi protein 73 is a valuable serum marker for hepatocelluar carcinoma. Gut,2010,59(12):1687-1693.
[23] Yao MJ,Wang LJ,You H,et al. Serum gp73 combined AST and GGT reflects moderate to severe liver inflammation in chronic hepatitis B. Clin Chim Acta,2019,493:92-97.
[24] Cao Z,Li Z,Wang H,et al. Algorithm of Golgi protein 73 and liver stiffness accurately diagnoses significant fibrosis in chronic HBV infection. Liver Int,2017,37(11):1612.

血浆GP73联合肝脏硬度检测诊断乙型和丙型肝炎患者肝纤维化临床价值分析^*

Diagnostic values of plasma Golgi protein 73 and liver stiffness measurement combination for liver fibrosis in patients with hepatitis B and C

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