血清高尔基体蛋白73联合AST对慢性乙型肝炎患者显著肝脏炎症损伤的诊断效能

肝脏 ›› 2019, Vol. 24 ›› Issue (2): 133-137.

血清高尔基体蛋白73联合AST对慢性乙型肝炎患者显著肝脏炎症损伤的诊断效能

王春艳, 韩萍, 纪冬, 马丽君, 王晶晶, 邵清, 陈国凤

100039 北京解放军总医院第五医学中心肝硬化诊疗二中心(王春艳,纪冬,王晶晶,邵清,陈国凤),肿瘤放射治疗中心(韩萍);甘肃省定西市人民医院感染性疾病科(马丽君)

收稿日期:2018-07-16 发布日期:2020-04-10
通讯作者: 陈国凤,Email: guofengchen302@163.com;韩萍,Email: hanp1966@sina.com
基金资助:
首都临床特色应用研究特色课题(Z181100001718034);中华医学会临床医学科研专项基金(13071110496);菊梅肝胆病防治能力建设专项基金重点项目(2018JM1260120-003);中国肝炎防治基金会王宝恩肝纤维化研究基金重点项目(2011xjs0408);中国肝炎防治基金会王宝恩肝纤维化研究基金面上项目(CFHPC20151025)

The efficiency of serum GP73 combined with AST for diagnosing liver inflammation in patients with chronic hepatitis B

WANG chun-yan¹, HAN Ping², JI Dong¹, Ma Li-jun³, WANG jing-jing¹, SHAO Qing¹, CHEN Guo-feng¹

1. The Second Liver Cirrhosis Diagnosis and Treatment Center, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China;
2. Cancer Radiotherapy Center, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 10039, China;
3. Department of infectious diseases,People's Hospital of Ding Xi, Gansu 743000, China

Received:2018-07-16 Published:2020-04-10
Contact: CHEN Guo-feng, Email: guofengchen302@163.com; HAN Ping, Email: hanp1966@sina.com

摘要/Abstract

摘要： 目的探讨血清高尔基体蛋白73(Golgi protein 73,GP73)与慢性乙型肝炎(chronic hepatitis B,CHB)患者的肝脏炎症的相关性,评估GP73联合AST的无创诊断模型对显著肝脏炎症(≥G2)的诊断效能。方法选取CHB初治患者422例,ALT<2倍正常值上限(upper limit of normal value,ULN)的患者222例,ALT≥2倍ULN患者200例,全部进行GP73、AST、ALT及其他实验室指标检测。ALT<2×ULN的患者进行肝活检,分析GP73与肝组织病理炎症的相关性,采用二元Logistic回归方法建立无创诊断模型并绘制受试者工作特征(ROC)曲线评价对于显著肝脏炎症(≥G2)的诊断效能。结果 ALT<2×ULN的患者GP73水平显著低于ALT≥2×ULN的患者,中位数分别为50.68 ng/mL和110.6 ng/mL (P<0.01)。ALT<2×ULN的患者具有显著肝脏炎症(≥G2)及显著纤维化(≥S2)者分别为57例(25.7%)和110例(49.5%),显著肝脏炎症组(≥G2)的GP73水平高于无明显肝脏炎症组(G0-G1)(P<0.01),伴随肝脏炎症程度的增加,GP73水平逐渐升高且与肝组织病理的炎症呈正相关,相关系数为0.405(P<0.01)。Logistic回归构建的GP73联合AST的无创诊断模型诊断显著肝脏炎症的效能(≥G2)明显优于单独应用GP73、ALT以及AST,AUROC为0.836(95%CI:0.781~0.882),敏感度、特异度分别为75.44%、80.61% (P<0.01)。新模型采用≤2.88以及≥4.2的诊断界值可以使80.6%(175/222)的CHB患者避免行肝活检。结论血清GP73与CHB患者的肝脏炎症密切相关,应用GP73联合AST的无创诊断模型能够准确预测显著肝脏炎症,替代肝穿刺,用以判定ALT在2倍正常值以下的患者是否须进行抗病毒治疗,值得临床推广。

关键词: 肝炎,乙型,慢性, 高尔基体蛋白73, 显著肝脏炎症, 无创,模型

Abstract: Objective To investigate the correlation between serum Golgi protein 73 (GP73) and liver inflammation in patients with chronic hepatitis B (CHB), and to assess the diagnostic accuracy of the noninvasive model based on GP73 and aspartate aminotransferase (AST) for significant liver inflammation (inflammation grade ≥G2).Methods A total of 422 treatment-nave CHB patients were divided into group 1 [whose alanine aminotransferase (ALT) ＜ 2×upper limit of normal (ULN), n=220] and group 2 (whose ALT ≥ 2×ULN, n=200). GP73, AST, ALT and other biochemical indices were detected in all patients. Patients in group 1 were with liver biopsy (LB), and the correlation between GP73 and pathological inflammation of liver tissue was analyzed. The noninvasive diagnostic model was established using binary logistic regression analysis and the diagnostic efficacy of significant hepatic inflammation (≥G2) was evaluated using receiver-operating characteristic (ROC) curve.Results GP73 level of group 1 (median, 50.68 ng/mL) was significantly lower than that of group 2 (median, 110.6 ng/mL)(P<0.001). In group 1, 57 cases (25.7%) and 110 cases (49.5%) showed significant hepatic inflammation (≥G2) and fibrosis (fibrosis stage ≥S2), respectively. The GP73 level of the significant hepatic inflammatory group (≥G2) was higher than that of invisible hepatic inflammatory group (G0-G1) (P<0.001), which showed positive correlation with inflammation grades in group 1 (correlation coefficient=0.405, P<0.001). The efficiency of noninvasive diagnosis model based on GP73 combined with AST in the diagnosis of significant liver inflammation (≥G2) was better than separate application of GP73, ALT or AST. The area under the ROC curve of this model was 0.836, and its sensitivity and specificity were 75.44% and 80.61% (P<0.01), respectively. When the cut-off values were ≤2.88 and ≥ 4.2, 80.6% (175/222) treatment-nave CHB patients could use this noninvasive diagnosis model without resorting to LB.Conclusion Serum GP73 level is closely correlated with liver inflammation in CHB patients. The noninvasive diagnostic model of GP73 combined with AST can accurately predict significant liver inflammation. It can be used as an alternative for LB to determine whether patients with ALT less than 2ULN need antiviral therapy or not.

Key words: Chronic hepatitis B, Golgi protein 73, Significant liver inflammation, Noninvasive model

王春艳, 韩萍, 纪冬, 马丽君, 王晶晶, 邵清, 陈国凤. 血清高尔基体蛋白73联合AST对慢性乙型肝炎患者显著肝脏炎症损伤的诊断效能[J]. 肝脏, 2019, 24(2): 133-137.

WANG chun-yan¹, HAN Ping², JI Dong¹, Ma Li-jun³, WANG jing-jing¹, SHAO Qing¹, CHEN Guo-feng¹. The efficiency of serum GP73 combined with AST for diagnosing liver inflammation in patients with chronic hepatitis B[J]. Chinese Hepatolgy, 2019, 24(2): 133-137.

参考文献

[1] Huang H, Sun Z, Pan H, et al. Serum metabolomic signatures discriminate early liver inflammation and fibrosis stages in patients with chronic hepatitis B. Sci Rep, 2016,6: 30853.
[2] Cheong JY, Kim DJ, Hwang SG, et al. Serum markers for necroinflammatory activity in patients with chronic viral hepatitis and normal or mildly elevated aminotransferase levels. Liver Int,2011, 31: 1352-1358.
[3] 许正锯,潘兴南,魏梅娟,等. 血清GP73对慢性乙型肝炎病毒携带者肝脏炎症损伤的预测价值.胃肠病学和肝病学杂志,2016,25:647-651.
[4] Mao Y, Yang H, Xu H,et al. golgi protein 73 (golph2) is a valuable serum marker for hepatocellular carcinoma.Gut,2010,59:1687-1693.
[5] 杨涛,刘伣,邹继华,等. 血清AFU联合GP73在原发性肝癌诊断中的应用价值.国际检验医学杂志,2017,38:1808-1811.
[6] Liu T, Yao M, Liu S,et al. Serum Golgi protein 73 is not a suitable diagnostic marker for hepatocellular carcinoma.Oncotarget,2017,8:16498-16506.
[7] 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,2017,37:1612-1621
[8] 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.中华医院感染学杂志,2016,26:2529-2543.
[9] 王贵强,王福生,成军,等. 慢性乙型肝炎防治指南(2015年版). 中华实验和临床感染病杂志(电子版), 2015,9: 570-589.
[10] 中华医学会传染病与寄生虫病学、肝病学分会. 病毒性肝炎防治方案. 中华传染病杂志,2001,19:56-62.
[11] 王晶晶,陈国凤. 无创肝纤维化诊断研究进展.肝脏,2018,23:72-76.
[12] Said Y, Mensi A, Khedher S, et al. Hemoperitoneum secondary to injury of cystic artery: rare and serious complication of liver biopsy. Tunis Med, 2017,95:506-507.
[13] Sumida Y, Nakajima A, Itoh Y, et al. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.World J Gastroenterol,2014,20:475-485.
[14] Xu Z, Shen J, Pan X,et al. Predictive value of serum Golgi protein 73 for prominent hepatic necroinflammation in chronic HBV infection. J Med Virol,2018,90: 1053-1062.
[15] 许正锯,潘兴南,魏开鹏,等. 血清高尔基体蛋白73与慢性乙型肝炎病毒感染者肝脏炎症损伤的相关性.中华实验和临床感染病杂志(电子版),2014,8:598-604.
[16] 许正锯,潘兴南,魏梅娟,等. 慢性乙型肝炎病毒感染者恩替卡韦抗病毒治疗前后血清高尔基体蛋白GP73的变化.中华实验和临床感染病杂志(电子版),2016,10:298-303.
[17] 应盛,高国生,董飞波,等. 血清GP73对慢加急性肝衰竭患者短期预后的评价.中华医院感染学杂志,2016,26:4894-4896.