1、HBV 慢性感染患者血清 ANGPTL 3 4 6 水平临床价值研究金梦琳韩雨晴王玉娴张军基金项目:安徽省教育厅重点项目(编号:KJ2018A1024)作者单位:233000安徽蚌埠蚌埠医学院第一附属医院医院检验科(金梦琳，韩雨晴，王玉娴)，输血科(张军)通信作者:张军，13909652118163 com 摘要 目的应用 Luminex 液相芯片技术检测血管生成素样蛋白(ANGPTL)3、4、6 在乙型肝炎病毒(HBV)慢性感染患者血清中表达水平及变化趋势，探究其临床意义。方法选取 2020 年 9 月至 2021 年 1 月就诊于蚌埠医学院第一附属医院的 64 例HBV 慢性感染患者为 H
2、BV 慢性感染组，包含肝癌(HCC 组)患者 18 例和非肝癌(非 HCC 组)患者 46 例，其中非 HCC 组进一步分为慢性乙型肝炎(CHB)组(n=24)和肝硬化(LC)组(n=22)，同时随机选取排除肝胆系统疾病的 18 例健康者作为对照组。收集研究对象的血清样本及相关临床资料数据，检测 ANGPTL 3、4、6 和肿瘤坏死因子 (TNF )、胆碱酯酶(CHE)血清水平，运用受试者工作特征(OC)曲线评估其对 HBV 慢性感染者发生 HCC 的诊断价值。结果与对照组相比，HBV 慢性感染组血清中 CHE、AN-GPTL 3、ANGPTL 6 水平降低(P 0 05)，ANGPTL 4、
3、TNF 水平升高(P 0 05)。CHB 组、LC 组、HCC 组 3 组间血清 ANGPTL 4、TNF 水平呈升高趋势，HCC 组与 CHB 组、LC 组间血清 ANGPTL 4、TNF 水平差异均有统计学意义(P 0 05);ANGPTL 6 水平呈下降趋势，CHB 与 HCC 组间 ANGPTL 6 水平差异有统计学意义(P 0 05);CHE 在 CHB 患者中较其他两组都高且分别与 LC、HCC 组间差异都有统计学意义(P 0 05)。与非 HCC 组相比，HCC 组患者血清 ANGPTL 4、TNF 水平升高(P 0 05)，ANGPTL6 水平降低(P 0 05)。ANGPTL
4、 4、TNF 单独检测评估 HBV 感染者 HCC 发生时 OC 曲线下面积(AUC)分别为 0 762、0 779，ANGPTL 4 检测灵敏度为 83 33%，优于 TNF 单独检测及 ANGPTL 4+TNF 联合检测时的灵敏度，但特异度仅 58 69%。AN-GPTL 4+TNF 联合检测时 AUC 为 0 804，特异度(78 26%)优于单因子检测，灵敏度为 72 22%。结论HBV 慢性感染患者血清 ANGPTL 3、4 水平下降，ANGPTL 6 水平上升且 ANGPTL 4 与 TNF 联合检测评估 HBV 慢性感染者患 HCC 的诊断价值优于单独检测。关键词 慢性乙型肝炎;
5、肝癌;血管生成素样蛋白 4;肿瘤坏死因子 doi:10.3969/j.issn.1000 0399.2023.01.005The clinical value study of serum ANGPTL 3 4 6 levels in patients with chronic infection with HBVJIN Menglin1，HAN Yuqing1，WANG Yuxian1，ZHANG Jun21 Department of Clinical Laboratory，First Affiliated Hospital of Bengbu Medical College，Bengbu
6、 233000，China2 Department of Blood Transfusion，First Affiliated Hospital of Bengbu Medical College，Bengbu 233000，ChinaFound project:Key Project of Anhui Provincial Education Department(No KJ2018A1024)Corresponding author:Zhang Jun，13909652118163 com Abstract Objectiveto detect the expression levels
7、and trends of angiopoietin like protein(ANGPTL)3，4 and 6 in the serumof HBV chronically infected patients via the application of Luminex liquid phase microarray technology，and to investigate its clinical signifi-cance MethodsA total of 64 patients with chronic HBV infection admitted to the First Aff
8、iliated Hospital of Bengbu Medical College fromSeptember 2020 to January 2021 were selected as the HBV chronic infection group，including 18 patients with liver cancer(HCC group)and46 patients with non liver cancer(non HCC group)，among which the non HCC group was further divided into chronic hepatiti
9、s B(CHB)group(n=24)and liver cirrhosis(LC)group(n=22)，while 18 healthy individuals with excluded hepatobiliary system diseaseswere randomly selected as the control group Serum samples and related clinical data of the subjects were collected，and the serum levels ofANGPTL 3，4，6，tumor necrosis factor (
10、TNF )and cholinesterase(CHE)were detected，and the diagnostic value of the subjectswith chronic HBV infection was evaluated by using the receiver working characteristics(OC)curve esultsCompared with the controlgroup，the serum levels of CHE，ANGPTL 3 and ANGPTL 6 were reduced(P 0 05)，and the levels of
11、ANGPTL 4 and TNF wereraised(P 0 05)in the HBV chronic infection group The levels of serum ANGPTL 4 and TNF between the CHB，LC and HCC groupsshowed an increasing trend，and the levels of serum ANGPTL 4 and TNF between the HCC group and the CHB group and the LC grouphad statistically significant differ
12、ence(P 0 05)The level of ANGPTL 6 showed a downward trend，and the difference between CHB andHCC groups was statistically significant(P 0 05)There were significant differences between HCC groups(P 0 05)Compared with the22安徽医学第 44 卷第 1 期Anhui Medical Journal2023 年 1 月non HCC group，serum ANGPTL 4 and T
13、NF levels increased(P 0 05)and ANGPTL 6 levels decreased(P 0 05)in the HCCgroup The area under the OC curve(AUC)under the OC curve(AUC)was 0 762 and 0 779 when liver cancer in HBV infected pa-tients was evaluated by ANGPTL 4 and TNF alone，respectively，and the sensitivity of ANGPTL 4 detection was 83
14、 33%，which was bet-ter than the sensitivity of TNF alone and ANGPTL 4+TNF combined detection，but the specificity was only 58 69%The AUC ofANGPTL 4+TNF was 0 804，and the specificity(78 26%)was better than that of single factor detection，and the sensitivity was72 22%ConclusionsSerum ANGPTL 3 and ANGPT
15、L 4 levels decrease and ANGPTL 6 levels increase in HBV chronic infected patientsThe diagnostic value of combined detection of ANGPTL 4 and TNF in patients with HBV chronic infection is better than that of alone inthe evaluation of liver cancer in patients with chronic HBV infection Key words Chroni
16、c hepatitis B;Hepatocellular carcinoma;Angiopoietin like protein 4;Tumor necrosis factor 据世界卫生组织1 报告，全世界大约有二十亿人曾经感染过乙型肝炎病毒(hepatitis B virus，HBV)，三亿五千万人是慢性感染者，每年因 HBV 感染引起的各类并发症死亡人数约为一百万。HBV 感染者若没有得到及时医治，很可能发展为慢性乙型肝炎(chronichepatitis B，CHB)，CHB 患者 5 年内累计的肝硬化(liv-er cirrhosis，LC)发生率为 8%20%，每年 LC 患者罹患肝癌(hepatocellular carcinoma，HCC)风险为 2%5%2。全球由 CHB 发展为 LC 和 HCC 的患者比例分别为 30%和 45%，而在我国则高达 60%和 80%3。HCC 现已成为我国最常见的恶性肿瘤之一4，但目前仍缺乏对其早期诊断的特异性血清标志物，传统的HCC 诊断肿瘤标志物如甲胎蛋白(alpha fetoprotein，AFP)存在一定假阳性，在不同人群、不