| 142 | 0 | 44 |
| 下载次数 | 被引频次 | 阅读次数 |
慢性乙型肝炎病毒（Hepatitis B virus, HBV）感染是一个全球公共卫生问题，若抗病毒治疗不及时可导致疾病发展为慢性乙型肝炎（Chronic hepatitis B, CHB）、肝硬化和肝细胞癌（Hepatocellular carcinoma, HCC）等疾病，严重影响患者健康。近年来，血清炎症因子及免疫功能指标在慢性HBV感染中的应用逐渐受到关注，对临床评估肝功能损伤程度和疾病发展进程具有重要价值。本文综述了血清炎症因子及免疫功能指标在慢性HBV感染中的作用，以及在疾病诊断、治疗监测和预后评估中的应用进展，以期为临床诊疗慢性HBV感染提供科学参考依据。
Abstract：Chronic hepatitis B virus(HBV) infection remains a major global public health concern. Without timely antiviral therapy, it can progress to chronic hepatitis B(CHB), liver cirrhosis, and hepatocellular carcinoma(HCC), posing serious threats to patient health. In recent years, increasing attention has been paid to the clinical utility of serum inflammatory markers and immune function indicators in chronic HBV infection. These biomarkers play a significant role in assessing the extent of hepatic injury and tracking disease progression. This review summarizes recent progress on the role of these indicators in the diagnosis, therapeutic monitoring, and prognostic evaluation of chronic HBV infection, aiming to provide a scientific basis for improved clinical management.
[1]Liu Z,Lin C,Mao X,et al.Changing prevalence of chronic hepatitis B virus infection in China between 1973and 2021:a systematic literature review and metaanalysis of 3740 studies and 231 million people[J].Gut,2023,72(12):2354-2363.DOI:10.1136/gutjnl-2023-330691.
[2]Huang L,Zhou L,Gan J,et al.IL-21 is associated with virological relapse of HBeAg positive chronic hepatitis B after discontinuance of entecavir[J].Turk J Gastroenterol,2021,32(2):178-186.DOI:10.5152/tjg.2021.19703.
[3]Ghenea AE,Pǎdureanu V,CioboatǎR,et al.The study of clinical and biochemical parameters in assessing the response to the antiviral therapy in the chronic viral hepatitis B[J].Medicina(Kaunas),2021,57(8):757.
[4]Zhou F,Xiong H,Zhen S,et al.Serum levels of IL-12,IL-18,and IL-21 are indicators of viral load in patients chronically infected with HBV[J].Braz J Med Biol Res,2022,55:e12320.DOI:10.1590/1414-431X2022e12320.
[5]吴耿刚,姚叶萍,姚金科,等.乙型肝炎病毒通过miR-183-5p/THBS1轴促进肝癌细胞的增殖、迁移和侵袭[J].病毒学报,2024,40(06):1290-1296.DOI:10.13242/j.cnki.bingduxuebao.004614.
[6]Zhang J,Liu Z,Liu L,et al.Th22/IL-22 mediates the progression of HBV-related hepatocellular carcinoma via STAT3[J].Cytotechnology,2022,74(2):203-216.DOI:10.1007/s10616-021-00517-9.
[7]Zheng JR,Wang ZL,Feng B.Hepatitis B functional cure and immune response[J].Front Immunol,2022,13:1075916.DOI:10.3389/fimmu.2022.10 75916.
[8]李维丹,石小霞,何竞月.妊娠期糖尿病合并HBV感染与妊娠结局研究进展[J].病毒学报,2025,41(01):257-263.DOI:10.13242/j.cnki.bingduxuebao.004654.
[9]李洁萍,王旭,富凡春,等.慢性乙型肝炎病毒感染患者血清IL-12和VEGF及IP-10蛋白水平与疾病进展的相关性[J].中华医院感染学杂志,2020,30(20):3047-3051.DOI:10.11816/cn.ni.2020-192518.
[10]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.DOI:10.3390/jpm13121675.
[11]侯静涛,许娟,闫涛涛,等.IL-18评价人工肝治疗HBV相关慢加急性肝衰竭有效性及短期预后效果的研究[J].西部医学,2024,36(7):987-991,997.DOI:10.3969/j.issn.1672-3511.2024.07.009.
[12]高子翔,沈忠良,刘晶,等.细胞因子在慢性乙型肝炎治疗中的研究进展[J].临床肝胆病杂志,2022,38(8):1710-1715.DOI:10.3969/j.issn.1001-5256.2022.08.002.
[13]Liu Q,Zhou Q,Wang M,et al.Interleukin-37suppresses the cytotoxicity of hepatitis B virus peptidesinduced CD8~+T cells in patients with acute hepatitis B[J].Biomol Biomed,2023,23(3):527-534.DOI:10.17305/bjbms.2022.8260.
[14]Yu F,Zhu Y,Li S,et al.Dysfunction and regulatory interplay of T and B cells in chronic hepatitis B:immunotherapy and emerging antiviral strategies[J].Front Cell Infect Microbiol,2024,14:1488527.DOI:10.3389/fcimb.2024.1488527.
[15]Liu C,Shih YF,Liu CJ.Immunopatho gene sis of acuteflare of chronic hepatitis B:with emphasis on the role of cytokines and chemokines[J].Int J Mol Sci,2022,23(3):1407.DOI:10.3390/ijms23031407.
[16]Hakim MS,Jariah ROA,Spaan M,et al.Interleukin15 upregulates the expression of PD-1 and TIM-3 on CD4~+and CD8~+T cells[J].Am J Clin Exp Immunol,2020,9(3):10-21.
[17]Khanam A,Ayithan N,Tang L,et al.IL-21-deficient T follicular helper cells support B cell responses through IL-27 in patients with chronic hepatitis B[J].Front Immunol,2021,11:599648.DOI:10.3389/fimmu.2020.599648.
[18]Ji L,Mei X,Yuan W,et al.Plasma interleukin-35levels predict the prognosis in patients with HBV-related acute-on-chronic liver failure[J].Viruses,2024,16(12):1960.DOI:10.3390/v16121960.
[19]Zhang Q,Yang L,Liu S,et al.Interleukin-35suppresses interleukin-9-secreting CD4+T cell activity in patients with hepatitis B-related hepatocellular carcinoma[J].Front Immunol,2021,12:645835.DOI:10.3389/fimmu.2021.645835.
[20]Zheng P,Dou Y,Wang Q.Immune response and treatment targets of chronic hepatitis B virus infection:innate and adaptive immunity[J].Front Cell Infect Microbiol,2023,13:1206720.DOI:10.3389/fcimb.2023.1206720.
[21]Zhang J,Liu K,Zhang G,et al.Interleukin-17A pretreatment attenuates the anti-hepatitis B virus efficacy of interferon-alpha by reducing activation of the interferon-stimulated gene factor 3 transcriptional complex in hepatitis B virus-expressing HepG2 cells[J].Virol J,2022,19(1):28.DOI:10.1186/s12985-022-01753-x.
[22]Adu F,Aniakwaa-B onsu E,Badu Nyarko S,et al.Host cytokine genetic polymorphisms in a selected population of persons living with hepatitis B virus infection in the central region of Ghana[J].BMC Gastroenterol,2024,24(1):374.DOI:10.1186/s12876-024-03456-9.
[23]Gu Y,Lian Y,Zheng Q,et al.Association among cytokine profiles of innate and adaptive immune responses and clinical-virological features in untreated patients with chronic hepatitis B[J].BMC Infect Dis,2020,20(1):509.DOI:10.1186/s12879-020-05233-x.
[24]段瑞娴,王艳,王熙苑,等.miR-199a-5p、IFN-γ、IL-12在老年慢性HBV感染患者不同免疫状态下的评估价值[J].中国老年学杂志,2023,43(11):2623-2626.
[25]Faure-Dupuy S,Baumert TF.Targeting immunometabolism and anti-viral immune responses in chronic hepatitis B[J].Hepatol Int,2023,17(5):1075-1078.DOI:10.1007/s12072-023-10546-5.
[26]Wang L,Zeng X,Wang Z,et al.Recent advances in understanding T cell activation and exhaustion during HBV infection[J].Virol Sin,2023,38(6):851-859.DOI:10.1016/j.virs.2023.10.007.
[27]Xie S,Yang L,Bi X,et al.Cytokine profiles and CD8+T cells in the occurrence of acute and chronic hepatitis B[J].Front Immunol,2022,13:1036612.DOI:10.3389/fimmu.2022.1036612.
[28]Yin GQ,Chen KP,Gu XC.Heterogeneity of immune control in chronic hepatitis B virus infection:Clinical implications on immunity with interferon-α treatment and retreatment[J].World J Gastroenterol,2022,28(40):5784-5800.DOI:10.3748/wjg.v28.i40.5784.
[29]杨杨,刘付弟,曾方林.人类免疫缺陷病毒/乙型肝炎病毒合并感染者CD4~+T细胞计数和乙型肝炎病毒复制、中性粒细胞与淋巴细胞比值水平的相关性[J].中国医药导报,2023,20(10):145-148.DOI:10.20047/j.issn1673-7210.2023.10.33.
[30]范清琪,汪婷,陈沛冬,等.HBeAg阳性慢性乙型病毒性肝炎患者外周血中分泌IL-21的CD4~+T细胞频数的检测及临床意义[J].中国感染与化疗杂志,2021,21(6):659-663.DOI:10.16718/j.1009-7708.2021.06.004.
[31]胡接力,黄爱龙.慢性乙型肝炎病毒感染与细胞免疫[J].中华微生物学和免疫学杂志,2023,43(7):494-501.DOI:10.3760/cma.j.cn112309-20230619-00179.
[32]Lin N,Yin W,Miller H,et al.The role of regulatory T cells and follicular T helper cells in HBV infection[J].Front Immunol,2023,14:1169601.DOI:10.3389/fimmu.2023.1169601.
[33]Cai Y,Yin W.The multiple functions of B cells in chronic HBV infection[J].Front Immunol,2020,11:582292.DOI:10.3389/fimmu.2020.582292.
[34]翁奉武,郭丽颖,李秋伟,等.外周血淋巴细胞亚群在慢性H B V感染过程中表达的变化分析[J].临床肝胆病杂志,2020,36(1):65-69.DOI:10.3969/j.issn.1001-5256.2020.01.015.
[35]汪海燕,鲍春梅,冯芷倩,等.慢性乙型肝炎患者外周血B淋巴细胞亚群的变化特征及临床意义[J].解放军医学杂志,2024,49(5):511-518.DOI:10.11855/j.issn.0577-7402.0566.2024.0108.
[36]Liu Y,Luo Y,Zhu T,et al.Regulatory B cells dysregulated T cell function in an IL-35-dependent wayin patients with chronic hepatitis B[J].Front Immunol,2021,12:653198.DOI:10.3389/fimmu.2021.653198.
[37]De Pasquale C,Campana S,Barberi C,et al.Human hepatitis B virus negatively impacts the protective immune crosstalk between natural killer and dendritic cells[J].Hepatology,2021,74(2):550-565.DOI:10.1002/hep.31725.
[38]Kupke P,Brucker J,Wettengel JM,et al.Cytokine response of natural killer cells to hepatitis B virus infection depends on monocyte co-stimulation[J].Viruses,2024,16(5):741.DOI:10.3390/v16050741.
[39]Dumolard L,Hilleret MN,Costentin C,et al.Differences in the intrahepatic expression of immune checkpoint molecules on T cells and natural killer cells in chronic HBV patients[J].Front Immunol,2025,15:1489770.DOI:10.3389/fimmu.2024.1489770.
[40]Wang J,Hou H,Mao L,et al.TIG IT signaling pathway regulates natural killer cell function in chronic hepatitis B virus infection[J].Front Med(Lausanne),2022,8:816474.DOI:10.3389/fmed.2021.816474.
[41]Fisicaro P,Barili V,Rossi M,et al.Pathogenetic mechanisms of T cell dysfunction in chronic HBV infection and related therapeutic approaches[J].Front Immunol,2020,11:849.DOI:10.3389/fimmu.2020.00849.
[42]Zhou C,Zhang N,He TT,et al.High levels of serum interleukin-6 increase mortality of hepatitis B virusassociated acute-on-chronic liver failure[J].World J Gastroenterol,2020,26(30):4479-4488.DOI:10.3748/wjg.v26.i30.4479.
[43]Yang JR,Wang J,Li HM,et al.IL-6 promoter hypomethylation acts As a diagnostic biomarker in hepatitis B virus-associated hepatocellular carcinoma[J].Front Oncol,2022,12:746643.DOI:10.3389/fonc.2022.746643.
[44]张文良,刘正金,甘海忠,等.乙型肝炎病毒感染患者病毒载量对血清炎症因子、免疫功能指标及肝功能指标影响[J].临床军医杂志,2020,48(7):856-857.DOI:10.16680/j.1671-3826.2020.07.44.
[45]Zhou D,Liu L,Liu J,et al.A systematic review of the advances in the study of T lymphocyte suppressor receptors in HBV infection:potential therapeutic targets[J].J Clin Med,2024,13(5):1210.DOI:10.3390/jcm13051210.
[46]Xu H,Kang J,Zhong S,et al.Function and autophagy of monocyte-derived dendritic cells is affected byhepatitis B virus infection[J].BMC Immunol,2023,24(1):31.DOI:10.1186/s12865-023-00571-2.
[47]Asandem DA,Segbefia SP,Kusi KA,et al.Hepatitis B virus infection:a mini review[J].Viruses,2024,16(5):724.DOI:10.3390/v16050724.
[48]Su Z,Chen J,Zhang J,et al.Circulating IL-1 β,IL-17,and IP-10 as potential predictors of hepatitis B virus infection prognosis[J].J Immunol Res,2022,2022:5202898.DOI:10.115 5/2022/5202898.
[49]Lin MJ,Su TH,Liu CJ,et al.Serum cytokine profiles predict outcomes of chronic hepatitis B patients discontinuing entecavir or tenofovir therapy[J].J Formos Med Assoc,2023,122(7):564-573.DOI:10.1016/j.jfma.2023.02.002.
[50]Holmberg M,Aass HCD,Dalgard O,et al.Treatment cessation in HBeAg-negative chronic hepatitis B:clinical response is associated with increase in specific pro inflammatory cytokines[J].Sci Rep,2023,13(1):22590.DOI:10.10 38/s415 98-023-50216-y.
[51]Yu XQ,Zhang XX.Research progress in host immune response during hepatitis B virus infection[J].Chin Med J(Engl),2020,133(22):2746-2748.DOI:10.1097/CM9.0000000000001096.
[52]Huang Y,Ju T,Zhang H,et al.Lower level of IL-28A as a predictive index of the artificial liver support system in effective treatment of patients with HBV-ACLF[J].J Clin Lab Anal,2022,36(12):e24766.DOI:10.1002/jcla.24766.
[53]毛静,刘鑫华,杨军杰,等.炎症和免疫指标对乙型肝炎病毒感染相关慢加急性肝衰竭预后判断价值研究进展[J/OL].中国肝脏病杂志(电子版),2024,16(1):18-21.DOI:10.3969/j.issn.1674-7380.2024.01.004.
[54]Cai Y,Ji H,Zhou X,et al.Interleukin-21 modulates balance between regulatory T cells and T-helper 17 cells in chronic hepatitis B virus infection[J].BMC Infect Dis,2023,23(1):719.DOI:10.1186/s12879-023-08723-w.
[55]Cai F,Zhao Y,Chen Q,et al.Serum cytokine analysis reveals predictors of progression from chronic hepatitis B to liver cirrhosis[J].Folia Biol(Praha),2021,67(1):28-36.DOI:10.14712/fb20210 6 7010028.
[56]Elbrolosy AM,Elabd NS,ElGedawy GA,et al.Tolllike receptor 2 polymorphism and IL-6 profile in relation to disease progression in chronic HBV infection:a case control study in Egyptian patients[J].Clin Exp Med,2023,23(1):117-129.DOI:10.1007/s10238-022-00792-6.
[57]董转丽,肖丽昕,付婷,等.炎症因子介导乙型肝炎病毒感染后机体免疫反应的研究进展[J].中华老年多器官疾病杂志,2022,21(9):704-706.DOI:10.11915/j.issn.1671-5403.2022.09.153.
[58]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.DOI:10.1186/s13027-024-00580-9.
基本信息:
DOI：10.13242/j.cnki.bingduxuebao.250208
中图分类号:R512.62
引用信息:
[1]肖荣,肖丽萍,王美华,等.血清炎症因子及免疫功能指标在慢性乙型肝炎病毒感染中的应用进展[J].病毒学报,2025,41(05):1600-1608.DOI:10.13242/j.cnki.bingduxuebao.250208.
基金信息: