血清β-arrestin 2、HIF-1a及CA125联合预测慢性乙型肝炎肝纤维化的价值

肝脏 ›› 2024, Vol. 29 ›› Issue (5): 521-525.

血清β-arrestin 2、HIF-1a及CA125联合预测慢性乙型肝炎肝纤维化的价值

汪蕾, 陈晨, 华喜梅, 胡丰芬

223800 江苏宿迁市第一人民医院医学检验科(汪蕾),普外肝胆(陈晨);223600 宿迁市沭阳县疾控中心检验科(华喜梅);223800 宿迁市沭阳县中医院医学检验科(胡丰芬)

收稿日期:2023-06-09 出版日期:2024-05-31 发布日期:2024-08-28
通讯作者: 陈晨,Email:cyogurtc@126.com
基金资助:
江苏省科技厅社会发展重点项目(BE2019638)

The value of a combination of serum β-arrestin 2, HIF-1α and CA125 to predict hepatic fibrosis in chronic hepatitis B patients

WANG Lei¹, CHEN Chen², HUA Xi-mei³, HU Feng-fen⁴

1. Department of Medical Laboratory, Suqian First People′s Hospital, Jiangsu 223800, China;
2. General Surgery Hepatobiliary Department, Suqian First People′s Hospital, Jiangsu 223800, China;
3. Laboratory of Shuyang County Center for Disease Control and Prevention, Jiangsu223600, China;
4. Department of Medical Laboratory, Shuyang County Traditional Chinese Medicine Hospital, Jiangsu 223800, China

Received:2023-06-09 Online:2024-05-31 Published:2024-08-28
Contact: CHEN Chen,Email:cyogurtc@126.com

摘要/Abstract

摘要： 目的探讨血清β-抑制蛋白2(β-arrestin2)、缺氧诱导因子1a(hypoxia inducible factor1α, HIF-1a)及糖类抗原125(carbohydrate antigen 125, CA125)联合预测慢性乙型肝炎(chronic Hepatitis B, CHB)肝纤维化的价值。方法选择宿迁市第一人民医院于2019年5月—2022年5月收治的110例CHB患者为研究对象,设为观察组,另选同期于我院体检中心体检的110名健康者为对照组。比较两组血清β-arrestin2、HIF-1a、CA125水平、观察肝纤维化不同病理分期患者以上指标水平,另通过ROC明确以上指标联合预测CHB处于S4的价值,采用多因素logistic回归分析CHB处于S4的危险因素,采用Pearson相关性分析以上指标与肝硬化病理分期的相关性。结果与对照组相比,观察组血清β-arrestin2、HIF-1a、CA125水平均有显著升高(t=21.376、21.548、71.752, P<0.05);肝纤维化S1、S2、S3、S4患者的血清β-arrestin2、HIF-1a、CA125水平逐渐升高(F=140.309、63.837、82.963, P<0.05);经ROC分析证实血清β-arrestin2、HIF-1a、CA125水平均可用于CHB处于S4的预测中,曲线下面积分别为0.984、0.926、0.956,且联合诊断能够获得更高的曲线下面积0.999,均有P<0.05;多因素logistic回归分析显示,β-arrestin2≥96.37 pg/mL(OR=2.011, 95% CI: 1.211~3.339)、HIF-1a≥74.345 μg/L(OR=1.696, 95% CI: 1.026~2.804)、CA125≥173.27 U/mL(OR=2.117, 95% CI: 1.974~3.987)是CHB处于S4的危险因素;血清β-arrestin2、HIF-1a、CA125水平与CHB肝纤维化分期呈正相关(r=0.458、0.651、0.531,均有P<0.05)。结论血清β-arrestin2、HIF-1a、CA125水平均能用于预测CHB肝纤维化,当以上指标水平越高肝纤维化程度越重,且联合应用时的敏感度更高,多个参数联合诊断可进一步提高诊断结果的客观性以及准确率,减少漏诊、误诊情况的发生,值得临床推广。

关键词: 血清β-抑制蛋白2, 缺氧诱导因子1a, 糖类抗原125, 慢性乙型肝炎, 肝纤维化

Abstract: Objective To investigate the value of serum β-inhibitory protein 2 (β-arrestin 2), hypoxia-inducing factor 1α (HIF-1α) and carbohydrate antigen 125 (CA125) in the prediction of hepatic fibrosis in chronic hepatitis B (CHB) patients. Methods One hundred and ten CHB patients admitted from May 2019 to May 2022 were selected as the study subjects, and were set as the observation group. Another 110 healthy people who were examined in the physical examination center at the same period of time were selected as the control group. The serum β-arrestin 2, HIF-1α, CA125 were compared between the two groups of people, and the above indicators in patients with different pathological stages of liver fibrosis were observed. Receiver operating characteristic curve (ROC) analysis was used to determine the value of the above indexes in predicting liver fibrosis stage 4 (S4) in CHB patients., Multiple logistic regression analysis was used to identify the risk factors of S4 CHB, Pearson correlation analysis was used to analyze the correlation between the above indexes and the pathological stage of cirrhosis. Results Compared with the control group, serum β-arrestin2, HIF-1α and CA125 levels in observation group were significantly increased (t=21.376, 21.548, 71.752, P<0.05). The serum β-arrestin2, HIF-1α and CA125 levels were increased gradually in CHB patients with S1, S2, S3 and S4 of hepatic fibrosis (F=140.309, 63.837, 82.963, P<0.05). It was proved by ROC analysis that serum β-arrestin2, HIF-1α and CA125 levels could be used to predict S4 of CHB, with the areas under the curve (AUC) of 0.984, 0.926 and 0.956, respectively. The combined diagnosis could obtain a higher AUC as 0.999 (P<0.05). Multivariate logistic regression analysis showed that β-arrestin2≥96.37 pg/mL (OR=2.011, 95%CI: 1.211~3.339), HIF-1α≥74.345 μg/L (OR=1.696, 95%CI: 1.026~2.804), CA125≥173.27 U/mL (OR=2.117, 95%CI: 1.974~3.987) were risk factors for S4. Serum β-arrestin2, HIF-1a, CA125 levels were positively correlated with hepatic fibrosis stages in CHB patients (r=0.458, 0.651, 0.531, all P<0.05). Conclusion Serum β-arrestin2, HIF-1α and CA125 levels can all be used to predict liver fibrosis stages in CHB patients. The higher the level of the aboval indexes, the more severe in the degree of liver fibrosis. The sensitivity of a combined application was higher than individual index. A combined diagnosis with multiple parameters may further improve the objectivity and accuracy of the diagnosis, and reduce the occurrence of missed diagnosis and misdiagnosis. It provides a reliable basis for clinical practice thus worthy of clinical promotion.

Key words: Serum beta-inhibitory protein 2, Hypoxia-inducing factor 1α, Carbohydrate antigen 125, Chronic hepatitis B, Hepatic fibrosis

汪蕾, 陈晨, 华喜梅, 胡丰芬. 血清β-arrestin 2、HIF-1a及CA125联合预测慢性乙型肝炎肝纤维化的价值[J]. 肝脏, 2024, 29(5): 521-525.

WANG Lei, CHEN Chen, HUA Xi-mei, HU Feng-fen. The value of a combination of serum β-arrestin 2, HIF-1α and CA125 to predict hepatic fibrosis in chronic hepatitis B patients[J]. Chinese Hepatolgy, 2024, 29(5): 521-525.

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参考文献

[1] Yong Q T, Yan C, Hai- N C. A risk prediction model for hepatocellular carcinoma after hepatitis B surface antigen seroclearance: Considerations[J]. J Hepatol,2022,77(6):1722-1724.
[2] 周宇辰, 胡承光, 袁国盛, 等. 抗病毒联合抗肝纤维化治疗慢性乙型肝炎肝纤维化降低肝细胞癌发生:144周的前瞻性队列研究[J]. 南方医科大学学报,2019,39(6):633-640.
[3] 陈晓玲, 宋倩. 剪切波弹性成像和γ-谷氨酰转肽酶/血小板比用于诊断慢性乙型肝炎患者肝纤维化[J]. 中国医学影像技术,2020,36(10):1499-1503.
[4] Sadek K, Abouzed T, Nasr S, et al. Licochalcone B Ameliorates Liver Cancer via Targeting of Apoptotic Genes, DNA Repair Systems, and Cell Cycle Control[J]. Iran J Pharm Res,2020,19(4):372-386.
[5] Silin Z, Meilan Z, Jiaxin C, et al. Ginsenoside Compound K Regulates HIF-1α-Mediated Glycolysis Through Bclaf1 to Inhibit the Proliferation of Human Liver Cancer Cells[J]. Front Pharmacol,2020,11(7):583334-583334.
[6] 杨妍, 胡燕梅, 韩静, 等. 索拉非尼对老年原发性肝癌患者肝功能及血清AFP,CEA,CA125,CA19-9水平的影响[J]. 中国老年学杂志,2020,40(13):2753-2756.
[7] 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更新版)[J]. 中华肝脏病杂志,2015,23(12):888-905.
[8] 中国中西医结合学会消化系统疾病专业委员会. 肝纤维化中西医结合诊疗共识意见(2017年)[J]. 中国中西医结合消化杂志,2017,25(12):895-900.
[9] Aashish K, Deepak R, Satesh K. Letter to the editor: Hepatitis B virus genotype: A significant risk factor in determining which patients with chronic hepatitis B virus infection should undergo surveillance for hepatocellular carcinoma: The hepatitis B Alaska study[J].Hepatology,2022,76(3):63-64.
[10] 牛兴杰, 刘志慧, 崔凤梅, 等. 相关炎症指标预测慢性乙型肝炎患者肝纤维化程度的价值[J]. 中华医院感染学杂志,2020,30(5):703-708.
[11] 王春艳, 纪冬, 马丽君, 等. 慢性乙型肝炎患者血清高尔基体蛋白73及其与肝脏炎症及纤维化的相关性[J]. 解放军医学杂志,2019,44(6):503-507.
[12] 丁荣蓉, 陆伟, 王雁冰, 等. 采用瞬时弹性成像技术和血清标志物预测丙氨酸转氨酶轻度升高的慢性乙型肝炎患者肝纤维化程度[J]. 中华传染病杂志,2019,37(2):72-76.
[13] Jia J D, Jia C S, Nan L, et al. β-Arrestin2 deficiency attenuates oxidative stress in mouse hepatic fibrosis through modulation of NOX4[J]. Acta Pharmacol Sin,2021,42(7):1090-1100.
[14] Omar A M, Esteban A M, Xin Z, et al. Hepatocyte HIF-1 and Intermittent Hypoxia Independently Impact Liver Fibrosis in Murine Nonalcoholic Fatty Liver Disease[J]. Am J Respir Cell Mol Biol,2021,65(4):390-402.
[15] 邓弘扬, 魏丰贤, 张宇浩, 等. 新型血清学指标早期预测急性胰腺炎严重程度及预后的研究进展[J]. 中国免疫学杂志,2021,37(10):1274-1278.
[16] 郑顺杰, 胡旻, 胡美旭, 等. 桂枝茯苓丸联合米非司酮对老年子宫肌瘤患者血液流变学,免疫功能及血清CA125和血管内皮生长因子-C表达的影响[J]. 中国老年学杂志,2020,40(15):3194-3197.
[17] 牛志强, 李智伟. 慢性乙型肝炎肝纤维化无创诊断方法的研究进展[J]. 中华传染病杂志,2022,40(2):116-120.
[18] Schierwagen R, Dietrich P, Klein S, et al. beta-Arrestin2 is increased in liver fibrosis in humans and rodents[J]. Proc Natl Acad Sci U S A,2020,117(44):27082-27084.
[19] Luo B, Xiang D, Cao W, et al. Intestinal epithelial cell-specific deletion of Hif1a affects the hepatic energy metabolism in cholestasis induced liver injury[J]. FASEB J,2020,34(1):1-1.
[20] 孙宇峰, 张明新, 隋文君, 等. γ-干扰素释放试验联合肿瘤标志物CA-125在活动性肺结核诊断中的应用[J].中华医学杂志,2019,99(8):599-604
[21] 马恺, 黄宁, 周川平. 血清CA125水平与慢性乙型肝炎合并肝硬化患者发生肝纤维化相关性分析[J]. 贵州医药,2020,44(10):1630-1631.