乙型肝炎病毒感染者血清白细胞介素17、血小板与淋巴细胞比值、血管内皮细胞生长因子表达意义及与疾病进展的相关性探讨

doi:10.19871/j.cnki.xfcrbzz.2024.05.006

摘要/Abstract

摘要： 目的探讨乙型肝炎病毒（hepatitis B virus,HBV）感染者血清白细胞介素17（interleukin 17,IL17）、血小板与淋巴细胞比值（platelet to lymphocyte ratio,PLR）、血管内皮细胞生长因子（vascular endothelial growth factor,VEGF）表达意义及与疾病进展的相关性。方法选择2022年6月至2024年3月昆山市第一人民医院收治的82例HBV感染者为研究组,根据病情进展程度将82例患者分为A组（慢性乙型肝炎）37例、B组（代偿期肝硬化）24例、C组（失代偿期肝硬化）21例,选择同期30例健康体检者为对照组。此外根据血清HBV DNA载量将HBV感染者分为阴性组18例（<1.0×10⁵copy/ml）、低载量组26例（1.0×10⁵~1.0×10⁸copy/ml）和高载量组38例（>1.0×10⁸copy/ml）。检测所有受试者的血清IL-17、PLR、VEGF表达水平及HBV DNA载量,分析血清IL-17、PLR、VEGF表达水平与疾病进展相关性。结果研究组患者血清IL-17、PLR、VEGF表达水平明显高于对照组（P<0.05）,C组患者血清IL-17、PLR、VEGF水平显著高于B组和A组,而B组患者血清IL-17、PLR、VEGF水平显著高于A组;高载量组患者血清IL-17、PLR、VEGF水平显著高于低载量组和阴性组,而低载量组患者血清IL-17、PLR、VEGF水平显著高于阴性组（均P<0.05）;Pearson相关系数分析血清IL-17、PLR、VEGF水平升高与HBV DNA载量、代偿期肝硬化、失代偿期肝硬化呈正相关（P<0.05）;多因素Logistic回归分析结果显示,IL-17、PLR、VEGF表达水平升高是疾病进展的危险因素（P<0.05）。血清IL-17、PLR、VEGF联合诊断代偿期肝硬化、失代偿期肝硬化的曲线下面积分别为0.823、0.835。结论血清IL-17、PLR和VEGF作为反映HBV感染及疾病进展的重要生物标志物,其水平变化与HBV DNA载量、代偿期肝硬化和失代偿期肝硬化密切相关。通过监测这些细胞因子的水平变化,有助于我们更准确地评估HBV感染者的病情严重程度及预后风险,为临床诊疗提供有价值的参考依据。

关键词: 乙型肝炎病毒, 白细胞介素17, 血小板与淋巴细胞比值, 血管内皮细胞生长因子, 疾病进展, 相关性

Abstract: Objective To investigate the significance of serum interleukin 17 (IL-17), platelet-to-lymphocyte ratio (PLR), and vascular endothelial growth factor (VEGF) expression and their correlation with disease progression in hepatitis B virus (HBV) infected patients. Method Eighty-two HBV-infected patients admitted from June 2022 to March 2024 were selected as the study group, and according to the degree of disease progression, the 82 patients were divided into 37 cases of group A (chronic hepatitis B), 24 cases of group B (compensated cirrhosis), and 21 cases of group C (decompensated cirrhosis), and 30 healthy medical check-ups were selected as the control group. In addition HBV-infected patients were classified into 18 cases of negative group (<1.0×10⁵copy/ml), 26 cases of low load group (1.0×10⁵~1.0×10⁸copy/ml) and 38 cases of high load group (>1.0×10⁸copy/ml) according to serum HBV DNA load. Serum IL-17, PLR, VEGF expression levels and HBV DNA load were detected in all subjects, and the correlation between serum IL-17, PLR, VEGF expression levels and disease progression was analysed. Result The serum IL-17, PLR, and VEGF expression levels of patients in the study group were significantly higher than those in the control group (P<0.05), and the serum IL-17, PLR, and VEGF levels of patients in group C were significantly higher than those in group B and group A, whereas those in group B were significantly higher than those in group A. The serum IL-17, PLR, and VEGF levels of patients in the high-load group were significantly higher than those in the low-load and negative groups, while serum IL-17, PLR, and VEGF levels in patients in the low-load group were significantly higher than those in the negative group (all P<0.05), Pearson correlation coefficient analyses of elevated serum IL-17, PLR, and VEGF levels were positively correlated with HBV DNA load, compensated cirrhosis, and decompensated cirrhosis (P<0.05), and multifactor Logistic regression analysis showed that elevated IL-17, PLR, and VEGF expression levels were all risk factors for disease progression (P<0.05). The AUCs for the combined diagnosis of compensated cirrhosis and decompensated cirrhosis using serum IL-17, PLR, and VEGF are 0.823 and 0.835, respectively. Conclusion As important biomarkers reflecting HBV infection and disease progression, changes in the levels of serum IL-17, PLR and VEGF are closely related to HBV DNA load, compensated cirrhosis and decompensated cirrhosis. By monitoring the changes in the levels of these cytokines, it helps us to more accurately assess the severity of the disease and prognostic risk of HBV-infected patients, and provides a valuable reference basis for clinical diagnosis and treatment.

Key words: Hepatitis B virus, Interleukin 17, Platelet to lymphocyte ratio, Vascular endothelial cell growth factor, Disease progression, Correlation

中图分类号:

R512.6+2

倪慧慧, 潘高峰, 陈舒君. 乙型肝炎病毒感染者血清白细胞介素17、血小板与淋巴细胞比值、血管内皮细胞生长因子表达意义及与疾病进展的相关性探讨[J]. 新发传染病电子杂志, 2024, 9(5): 31-35.

Ni Huihui, Pan Gaofeng, Chen Shujun. Expression significance of interleukin 17, platelet to lymphocyte ratio, vascular endothelial growth factor in serum of hepatitis B virus infected patients and their correlation with disease progression[J]. Electronic Journal of Emerging Infectious Diseases, 2024, 9(5): 31-35.

参考文献

[1] 代玉, 郭楠, 黄磊, 等. 慢性乙型肝炎病毒感染者低病毒血症的研究现状[J]. 传染病信息, 2023, 36(3):263-266,271.
[2] 陈欣欣, 张海萍, 黄春洋, 等. 有乙型肝炎病毒感染史的自身免疫性肝炎患者的病毒学特征分析[J]. 传染病信息, 2024, 37(1):5-10.
[3] 刘晓梦, 赵彩彦. 2017年感染性疾病临床进展[J]. 临床荟萃, 2018, 33(1):60-65.
[4] 李冰, 王树文, 程晓博, 等. 慢性乙型肝炎治疗的研究进展[J].青岛大学学报(医学版), 2022, 58(6):930-935.
[5] KAR A, SAMANTA A, MUKHERJEE S, et al.The HBV web:An insight into molecular interactomes between the hepatitis B virus and its host en route to hepatocellular carcinoma[J]. J Med Virol, 2023,95(1):28436.
[6] 张园园, 李俊洁, 吴丽娜, 等. 恩格列净对乙型病毒性肝炎合并T2DM患者的疗效与安全性[J].河南大学学报(医学版), 2022, 41(2):127-132.
[7] 张冬青, 林升龙, 马华皙, 等. 干扰素-λ3水平及白细胞介素28B基因多态性与乙型肝炎病毒相关慢加急性(亚急性)肝衰竭预后的关系[J/CD]. 新发传染病电子杂志, 2023, 8(6):42-46.
[8] 孙海荣, 冯伟广, 周冰清, 等. 不同血清ALT水平的乙型肝炎病毒感染者肝纤维化指标变化[J]. 实用肝脏病杂志, 2021, 24(4):488-491.
[9] DIMITRIADIS K, KATELANI S, PAPPA M, et al.The Role of Interleukins in HBV Infection:A Narrative Review[J]. J Pers Med, 2023,13(12):1675.
[10] JIA Y, JIAO X, SHI W, et al.Expression of 10 circulating cytokines/chemokines in HBV-related liver disease[J]. Infect Agent Cancer, 2024,19(1):20.
[11] TAVAKOLIAN S, TABAEIAN SP, NAMAZI A, et al.Role of the VEGF in virus-associated cancers[J]. Rev Med Virol, 2024, 34(1):2493.
[12] 郭晓冬, 余快, 李秋, 等. 术前血小板与淋巴细胞比值对乙型肝炎病毒相关肝细胞癌患者术后预后的影响[J]. 山西医药杂志, 2019, 48(4):399-402.
[13] 李黎, 崔富强, 张国民, 等. 乙型肝炎诊断标准(WS299-2008)解读[J]. 中华预防医学杂志, 2014, (9):758.
[14] 卫明珠, 潘继文, 罗锐, 等. 凝血4项和肿瘤标志物对乙型肝炎相关肝癌的辅助诊断价值[J]. 检验医学, 2023, 38(9):901-904.
[15] ULLAH N, KHAN I, KAKAKHEL MA, et al.Serological prevalence of hepatitis B virus (HBV) in Mardan district, Khyber Pakhtunkhwa, Pakistan[J]. Braz J Biol, 2021, 82(1):245813.
[16] WU LL, HUANG TS, SHYU YC, et al.Gut microbiota in the innate immunity against hepatitis B virus - implication in age-dependent HBV clearance[J]. Curr Opin Virol, 2021, 49(1):194-202.
[17] 王柳青, 李雅静, 薛素娟, 等. 恩替卡韦联合扶正化瘀胶囊治疗HBV感染失代偿期肝硬化患者的疗效及对血清炎性因子的影响[J].疑难病杂志, 2020, 19(10):985-989.
[18] ZHENG Y, WANG M, LI S, et al.Hepatitis B virus hijacks TSG101 to facilitate egress via multiple vesicle bodies[J]. PLoS Pathog, 2023, 19(5):1011382
[19] 亢必勃, 赵绒, 赵杨, 等. 血浆B细胞趋化因子1和干细胞因子水平与HBV感染患者临床指标的关系[J].基础医学与临床, 2023, 43(2):289-292.
[20] KRIDIN K, ZIRPEL H, MRUWAT N, et al.Evaluating the risk of infections under interleukin 23 and interleukin 17 inhibitors relative to tumour necrosis factor inhibitors - A population-based study[J]. J Eur Acad Dermatol Venereol, 2023,37(11):2319-2326.
[21] SUN HQ, JIA JH.IncreasedTh17 cells contribute to disease progression in patientswith HBV-associated liver cirrhosis[J]. J Viral Hepat, 2012, 19(6):396-403.
[22] 陈万义, 张庆民. 血清AFU、IL-17、CRP在乙型病毒性肝炎患者中的检测价值[J]. 检验医学与临床, 2019, 16(19):2797-2799, 2802.
[23] 陈天雷, 杨敏. 血小板/淋巴细胞比值与持续非卧床腹膜透析患者炎症状态的关系[J].中国血液净化, 2019, 18(7):473-476.
[24] 秦笙, 练立婷, 王维亮, 等. 广州发热呼吸道症候群成年患者临床特征及病原学检测[J].中国热带医学, 2016, 16(5):495-498.
[25] 李慧平, 侯宝洲, 魏思忱, 等.血清VEGF、TK-1和T淋巴细胞亚群与乙型肝炎病毒相关性肝病发生和进展的关系[J].蚌埠医学院学报, 2022, 47(10):1393-1396.
[26] CAI P, NI R, LV M, et al.VEGF signaling governs the initiation of biliary-mediated liver regeneration through the PI3K-mTORC1 axis[J]. Cell Rep, 2023, 42(9):113028.
[27] 夏雪皎, 林庚庭, 滕飞, 等. 疏肝健脾活血方对肝纤维化大鼠肝组织HIF-1α蛋白及VEGF mRNA表达的影响[J]. 中华中医药杂志, 2018, 33(4):1357-1360.
[28] 孙乐, 俞群力, 刘克伟. 血清TGF-β1及VEGF在慢性乙肝后肝纤维化、肝硬化患者的临床变化及其意义[J]. 现代诊断与治疗, 2014, 25(24):5633-5634.