[1]郭 堑,农村立,韦秋芳.慢性乙型肝炎肝纤维化患者血清Copeptin 和PCT 表达水平及其临床价值研究[J].现代检验医学杂志,2023,38(02):112-117+189.[doi:10.3969/j.issn.1671-7414.2023.02.021 ]
　GUO Qian,NONG Cun-li,WEI Qiu-fang.Serum Copeptin and PCT Expression Levels and Their Diagnostic Value in Patients with Hepatitis B Liver fibrosis[J].Journal of Modern Laboratory Medicine,2023,38(02):112-117+189.[doi:10.3969/j.issn.1671-7414.2023.02.021 ]
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慢性乙型肝炎肝纤维化患者血清Copeptin 和PCT 表达水平及其临床价值研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年02期
页码:
112-117+189
栏目:
论著
出版日期:
2023-03-15

文章信息/Info

Title:
Serum Copeptin and PCT Expression Levels and Their Diagnostic Value in Patients with Hepatitis B Liver fibrosis
文章编号:
1671-7414（2023）02-112-07
作者:
郭 堑; 农村立; 韦秋芳
（广西医科大学第四附属医院 /柳州市工人医院感染性疾病科，广西柳州 545005）
Author(s):
GUO Qian; NONG Cun-li; WEI Qiu-fang
（Department of Infectious Diseases, the Fourth Affiliated Hospital of Guangxi Medical University/Liuzhou Workers Hospital, Guangxi Liuzhou 545005, China）
关键词:
慢性乙型肝炎; 肝纤维化; 和肽素; 降钙素原
分类号:
R575.2；R392.11
DOI:
10.3969/j.issn.1671-7414.2023.02.021
文献标志码:
A
摘要:
目的 探讨慢性乙型肝炎肝纤维化患者血清和肽素（Copeptin）和降钙素原（procalcitonin ，PCT）表达水平，并分析其在肝纤维化诊断中的价值。方法 共纳入 2019年 2月 ~2021年 12月在广西医科大学第四附属医院就诊的 195例慢性肝病单感染 HBV患者作为 HBV组，并选择同一期间在该院进行健康体检的志愿者作为对照组。其中 HBV组中慢性乙型肝炎（CHB）患者 117例（CHB组）， CHB相关肝硬化（LC）患者 78例（LC组），对所有参与患者进行临床指标分析，采用 ELISA方法检测患者血清 Copeptin和 PCT表达水平。METAVIR评分系统评估 CHB组中接受肝活检的患者的肝纤维化程度； Child-Pugh分级评估 LC患者的肝功能障碍程度。比较 Copeptin，PCT表达水平与肝纤维化和肝功能的关系。 ROC曲线评估肝纤维化诊断生物标志物。结果 HBV组血清 Copeptin（2.39±0.73 ng/ml vs 1.19±0.39 ng/ml）和 PCT（2.11±0.69 ng/ml vs 0.97±0.31 ng/ml）水平明显高于对照组（t=11.912，12.108，均 P <0.05），并且与 CHB组比较， LC组血清 Copeptin（3.18±0.96 ng/ml vs 1.87±0.58 ng/ml）和 PCT（2.87±0.92 ng/ml vs 1.61±0.53 ng/ ml）表达水平增加（t=11.871，12.111，均 P<0.05），差异具有统计学意义。血清 Copeptin和 PCT表达水平随着肝纤维化程度和 Child-Pugh分级的增加而升高，差异有统计学意义（t=2.887~9.116，均 P <0.05）。血清 Copeptin和 PCT表达水平及其他无创方法 [肝脏硬度（LSM），AST与血小板比率指数（APRI）和纤维化 -4（fiB-4）指数 ]区分 CHB患者发生 F0~F1期与 F2~F3期肝纤维化的 ROC曲线下面积分别为 0.910，0.889，0.790，0.765和 0.672，而以上五项指标联合的曲线下面积为 0.962。Copeptin和 PCT区分 CHB患者肝纤维化程度的曲线下面积及总有效率高于肝纤维化指标（IV型胶原、III型前胶原、透明质酸酶、层黏连蛋白）。结论 血清 Copeptin和 PCT在慢性乙型肝炎肝纤维化患者中高表达，能够用于诊断肝纤维化程度。
Abstract:
Objective To determine the expression characteristics of serum Copeptin and procalcitonin (PCT) in patients with hepatitis B virus (HBV), and analyze their diagnostic value in liver fibrosis. Methods A total of 195 patients with chronic liver disease single-infected with HBV who were treated in the Fourth Affiliated Hospital of Guangxi Medical University from February 2019 to December 2021 were included as the HBV group, and volunteers who underwent physical examination in the hospital during the same period were selected as the control group. Among them, there were 117 patients with chronic hepatitis B (CHB) in the HBV group (CHB group), and 78 patients with CHB-related liver cirrhosis (LC) (LC group). The clinical indicators of all the participating patients were analyzed, and the serum Copeptin and PCT expression levels of the patients in each group were detected by ELISA. The METAVIR scoring system assessed the degree of liver fibrosis in patients in the CHB group who underwent liver biopsy. The Child-Pugh classification assessed the degree of liver dysfunction in patients with LC. The relationship between Copeptin and PCT expression levels and liver fibrosis and liver function were compared, and ROC curve evaluation of diagnostic biomarkers of liver fibrosis. Results The levels of serum Copeptin (2.39±0.73 ng/ml vs 1.19±0.39 ng/ml) and PCT (2.11±0.69 ng/ml vs 0.97±0.31 ng/ml) in the HBV group were significantly higher than those in the control group (t=11.912, 12.108, all P <0.05), and compared with the CHB group, the expression levels of serum Copeptin and PCT in the LC group increased (3.18±0.96 ng/ml vs 1.87±0.58 ng/ml, 2.87±0.92 ng/ml vs 1.61±0.53 ng/ml, t=11.871, 12.111, all P<0.05), and the difference were statistically significant. Serum Copeptin and PCT expression levels increased with the degree of liver fibrosis and Child-Pugh grade (t=3.666, 2.887, 9.116, 3.755, all P <0.05). Serum Copeptin, PCT expression levels and other non-invasive methods [liver stiffness (LSM), AST to platelet ratio index (APRI) and fibrosis-4 (fiB-4) index] to differentiate CHB patients with F0~F1 and F2~F3 stages the areas under the ROC curve of liver fibrosis were 0.910, 0.889, 0.790, 0.765 and 0.672, respectively, and the combined area under the curve of the above five indicators was 0.962. The area under the curve and total effective rate of Copeptin and PCT in differentiating the degree of liver fibrosis in CHB patients were higher than those of liver fibrosis indicators (type IV collagen, type III procollagen, hyaluronidase, laminin). Conclusion Serum Copeptin and PCT were highly expressed in patients with chronic hepatitis B liver fibrosis and can be used to diagnose the degree of liver fibrosis.

参考文献/References:

[1] 吴婕 , 张英杰 , 周华君 ,等 . 慢性 HBV感染者血清持续低水平 HBsAg表达免疫耐受机制的研究进展 [J]. 现代检验医学杂志 , 2022, 37(2):199-204. WU Jie, ZHANG Yingjie, ZHOU Huajun, et al. Research progress on immune tolerance mechanism of persistent low-level serum HBsAg expression in patients with chronic HBV infection [J]. Journal of Modern Laboratory Medicine, 2022, 37(2):199-204.
[2] XIE Guofeng, XU Yuxia, XU Fei, et al. Plasma SGIP1 methylation in diagnosis and prognosis prediction in hepatocellular carcinoma[J]. Neoplasma, 2021, 68(1):62-70.
[3] 孙龙 , 苏健 , 邓杨柳 ,等 . 乙型肝炎病毒剪接特异性蛋白在乙肝病毒感染相关肝细胞癌中的表达及意义 [J]. 中国老年学杂志 , 2021, 41(4): 773-775. SUN Long, SU Jian, DENG Yangliu, et al. Expression of hepatitis B virus splicing-specific protein in HBV infection-related liver disease and its correlation with cytokines[J]. Chinese Journal of Gerontology, 2021, 41(4): 773-775.
[4] YAN Linlin, DENG Yongqiong, ZHOU Jiyuan, et al. Serum YKL-40 as a biomarker for liver fibrosis in chronic hepatitis B patients with normal and mildly elevated ALT [J]. Infection, 2018, 46(3):385-393.
[5] 叶乃源 , 蒋佩岑 , 陈曦 ,等 . 弹性成像技术联合血清学模型评估乙型肝炎患者肝纤维化分期 [J]. 中国医学影像技术 , 2021 37(5):707-711. YE Naiyuan, JIANG Peicen, CHEN Xi, et al. Elasticity imaging techniques combined with serological models for evaluating the stage of hepatic fibrosis in chronic hepatitis B patients [J]. Chinese Journal of Medical Imaging Technology, 2021, 37(5):707-711.
[6] 王文玲 , 张馨元 , 叶松 ,等 . 丙氨酸氨基转移酶水平对 fibroTouch检测慢性乙型肝炎患者肝脏硬度值的影响研究 [J]. 中国全科医学 , 2021, 24(30):3842-3847. WANG Wenling, ZHANG Xinyuan, YE Song, et al. Impact of alanine aminotransferase level on liver stiffness measured by fibrotouch in patients with chronic hepatitis B [J]. Chinese General Practice, 2021, 24(30):3842-3847.
[7] SOLà E, KERBERT A J, VERSPAGET H W, et al. Plasma copeptin as biomarker of disease progression and prognosis in cirrhosis [J]. J Hepatol, 2016, 65(5):914-920.
[8] SATO S, SATO S, TSUZURA H, et al. Elevat-ed serum procalcitonin levels and their association with the prognosis of patients with liver cirrhosis[J]. European Journal of Gastroenterology and Hepatology, 2020, 32(9):1222-1228.
[9] ITAKURA J, KUROSAKI M, SETOYAMA H, et al. Applicability of APRI and fiB-4 as a transition indicator of liver fibrosis in patients with chronic viral hepatitis[J]. Journal of Gastroenterology, 2021, 56(5):470-478..
[10] 姚升娟 , 曲静琦 , 曹宇 ,等 . MRI联合血清 miR-204水平对原发性肝癌经皮穿刺射频消融术后疗效及复发的预测价值 [J]. 放射学实践 , 2022, 37(1):62-67. YAO Shengjuan, QU Jingqi, CAO Yu, et al. The predictive value of MRI combined with serum miR-204 level for the efficacy and recurrence of primary liver cancer after percutaneous radiofrequency ablation[J]. Radiologic Practice, 2022, 37(1):62-67.
[11] HUR M, PARK M, MOON H W, et al. Comparison of non-invasive clinical algorithms for liver fibrosis in patients with chronic hepatitis B to reduce the need for liver biopsy: application of enhanced liver fibrosis and mac-2 binding protein glycosylation isomer[J]. Ann Lab Med, 2022, 42(2):249-257.
[12] SUN Yameng, WU Xiaoning, ZHOU Jialing, et al. Persistent low level of hepatitis B virus promotes fibrosis progression during therapy[J]. Clin Gastroenterol Hepatol, 2020, 18(11):2582-2591.
[13] YANG Hui, WANG Juan, LIU Zhenguo. Multi-faceted role of pyroptosis mediated by inflammasome in liver fibrosis[J]. J Cell Mol Med, 2022, 26(10):2757-2765.
[14] ZHOU Xia, LIANG Ziyu, QIN Shanyu, et al. Serum-derived miR-574-5p-containing exosomes contribute to liver fibrosis by activating hepatic stellate cells[J]. Mol Biol Rep, 2022, 49(3):1945-1954.
[15] CHRIST-CRAIN M, REFARDT J, WINZELER B. Approach to the patient: “utility of the copeptin as-say”[J]. J Clin Endocrinol Metab, 2022, 107(6):1727-1738.
[16] SZMYGIN H, SZYDE?KO J, MATYJASZEK-MATUSZEK B. Copeptin as a novel biomarker of cardiometabolic syndrome[J]. Endokrynol Pol, 2021, 72(5):566-571.
[17] HEINRICH N S, THEILADE S, WINTHER S A, et al. Copeptin and renal function decline, cardiovascular events and mortality in type 1 diabetes[J]. Nephrol Dial Transplant, 2021, 37(1):100-107.
[18] KERBERT A J, WEIL D, VERSPAGET H W, et al. Copeptin is an independent prognostic factor for transplant-free survival in cirrhosis[J]. Liver Int, 2016, 36(4):530-537.
[19] OH J H, KWON J H, KIM H H, et al. One-step-immunoassay of procalcitonin enables rapid and accurate diagnosis of bacterial infection[J]. RSC Adv, 2021, 11(35):21375-21383.
[20] 曾宗鼎 , 邢崇浩 . 血清降钙素原及和肽素水平对危重患者医院获得性肺炎的预后评估价值 [J]. 中国急救医学 , 2017, 37(4):340-345. ZENG Zongding, XING Chonghao. Value of serum proealcitonin and copeptin in predicting prognosis of hospital - acquired pneumo- nia in critically ill patients [J]. Chinese Journal of Critical Care Medicine, 2017, 37(4):340-345.
[21] 窦红佳 , 韩钧凌 , 黄轶华 ,等 . 血清 Copeptin在慢性肝病显著纤维化和肝硬化中的诊断价值 [J].胃肠病学和肝病学杂志 , 2020, 29(1):78-82. DOU Hongjia, HAN Junling, HUANG Yihua, et al. Diagnostic value of serum Copeptin in significant fibrosis and cirrhosis of chronic liver disease [J]. Chinese Journal of Gastroenterology and Hepatology, 2020, 29(1):78-82.
[22] SHIGEFUKU R, IWASA M, EGUCHI A, et al. Serum Copeptin and Zinc-α2-glycoprotein levels are novel biomarkers of tolvaptan treatment in decompensated cirrhotic patients with ascites [J]. Intern Med, 2021, 60(21):3359-3368.
[23] 王传敏 , 孟忠吉 , 陈悦 , 等 . 血清降钙素原检测对肝衰竭合并感染的早期诊断价值 [J]. 临床肝胆病杂志 , 2017, 33(6):1137-1140.WANG Chuanmin, MENG Zhongjie, CHEN Yue, et al. Value of serum PCT in early diagnosis of bacterial infection in patients with liver failure [J]. Journal of Clinical Hepatology, 2017, 33(6):1137-1140.
[24] XU Minghao, XU Bin, ZHOU Chenhao, et al. An mALBI-Child-Pugh-based nomogram for predicting post-hepatectomy liver failure grade B-C in patients with huge hepatocellular carcinoma: a multi-institutional study[J]. World J Surg Oncol, 2022, 20(1):206.
[25] 陶苗苗 ,张炎 ,侯庆兵 . 瞬时弹性成像技术肝硬度值测定在胆汁淤积性肝纤维化病变进展中诊断价值研究 [J]. 临床军医杂志 ,2019,47(6):565-566. TAO Miaomiao, ZHANG Yan, HOU Qingbing. Study on the diagnostic value of transient elastography in the determination of liver stiffness in the progression of cholestatic liver fibrosis[J] .Clinical Journal of Medical Officers , 2019, 47(6):565-566.
[26] PAPADOPOULOS N , VASILEIADI S , PAPAVDI M, et al. Liver fibrosis staging with combination of APRI and fiB-4 scoring systems in chronic hepatitis C as an alternative to transient elastography[J]. Annals of Gastroenterology, 2019, 32(5):498-503.

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备注/Memo

备注/Memo:
收稿日期：2022-06-13修回日期：2022-10-27
基金项目：广西科技计划项目（编号：桂科 AB18050020）：肝细胞癌遗传靶标筛选与鉴定及风险评估模型的建立。
作者简介：郭堑（1970-），女，本科，主任医师，主要从事各类肝病、感染方面研究， E-mail：guoqian58200@163.com。

更新日期/Last Update: 2023-03-15