原发免疫性血小板减少症合并HBV感染的研究现状

黄梦贞; 何阳阳; 王诗轩

doi:10.3969/j.issn.1001-5256.2023.09.023

原发免疫性血小板减少症合并HBV感染的研究现状

DOI: 10.3969/j.issn.1001-5256.2023.09.023

1.
赣江新区人民医院血液科，南昌 330029
2.
南昌大学第二附属医院输血科，南昌 330006
3.
南昌大学第一附属医院血液病中心，江西省血液病临床医学研究中心，南昌 330006

基金项目:

国家自然科学基金 (82060030)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：黄梦贞负责文献查找、阅读及文章撰写；何阳阳对研究思路有贡献作用；王诗轩负责文章选题及修改。

详细信息

通信作者:
王诗轩， xiare_2009@163.com （ORCID： 0000－0003－4254－878X）

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- 被引次数: 0
出版历程
- 收稿日期: 2022-12-13
- 录用日期: 2023-01-15
- 出版日期: 2023-09-19

Current research status of primary immune thrombocytopenia with hepatitis B virus infection

1.
Department of Hematology，Ganjiang New Area People’s Hospital，Nanchang 330029，China
2.
Department of Blood Transfusion，The Second Affiliated Hospital of Nanchang University，Nanchang 330006，China
3.
Center of Hematology，The First Affiliated Hospital of Nanchang University，Institute of Hematology，Academy of Clinical Medicine of Jiangxi Province，Nanchang 330006，China

Research funding:

National Natural Science Foundation of China (82060030)

More Information

Corresponding author: WANG Shixuan， xiare_2009@163.com （ORCID： 0000－0003－4254－878X）

摘要

摘要: 原发免疫性血小板减少症（ITP）是一种以血小板破坏增加和生成障碍为特征的自身免疫性疾病。我国是HBV感染的高发区，临床上常发现ITP患者合并HBV感染，HBV感染不仅可以直接抑制血小板生成及加速血小板破坏，同时，还可以通过调节细胞免疫、体液免疫、固有免疫对ITP的发生、发展、临床特征及治疗产生一定的影响，且免疫抑制治疗可能使HBV再激活，使疾病复杂化。本文主要综述ITP合并HBV感染的免疫学特点、预后及治疗进展。
- 紫癜，血小板减少性，特发性 /
- 乙型肝炎病毒 /
- 治疗学 /
- 预后
Abstract: Primary immune thrombocytopenia （ITP） is an autoimmune disease characterized by increased platelet destruction and impaired production. There is a high incidence rate of hepatitis B virus （HBV） infection in China， and it is often observed in clinical practice that ITP patients are often comorbid with HBV infection. HBV infection can not only directly inhibit platelet production and accelerate platelet destruction， but also affect the development， progression， clinical features， and treatment of ITP by regulating cellular immunity， humoral immunity， and innate immunity， and immunosuppressive therapy may cause HBV reactivation and thus lead to complex disease conditions. This article mainly reviews the immunological characteristics， prognosis， and treatment of ITP with HBV infection.
- Purpura， Thrombocytopenic， Idiopathic /
- Hepatitis B Virus /
- Therapeutics /
- Prognosis

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参考文献(43)

[1]	NELSON VS, JOLINK AC, AMINI SN, et al. Platelets in ITP: Victims in charge of their own fate?[J]. Cells, 2021, 10( 11): 3235. DOI: 10.3390/cells10113235.
[2]	Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B(version 2019)[J]. J Clin Hepatol, 2019, 35( 12): 2648－ 2669. DOI: 10.3969/j.issn.1001－5256.2019.12.007. 中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35( 12): 2648－ 2669. DOI: 10.3969/j.issn.1001－5256.2019.12.007.
[3]	WANG Y, WANG XL. Analysis of the correlation between hepatitis B virus and thrombocytopenia[J]. Chin J Misdiagn, 2009, 9( 22): 5395. 王彦, 王笑蕾. 乙型肝炎病毒与血小板减少性症的相关性分析[J]. 中国误诊学杂志, 2009, 9( 22): 5395.
[4]	WU SR, KUO HC, HUANG WC, et al. Incidence, clinical characteristics, and associated diseases in patients with immune thrombocytopenia: A nationwide population－based study in Taiwan[J]. Thromb Res, 2018, 164: 90－ 95. DOI: 10.1016/j.thromres.2018.02.146.
[5]	MOULIS G, PALMARO A, MONTASTRUC JL, et al. Epidemiology of incident immune thrombocytopenia: a nationwide population－based study in France[J]. Blood, 2014, 124( 22): 3308－ 3315. DOI: 10.1182/blood－2014－05－578336.
[6]	SU TH, LIU CJ, TSENG TC, et al. Chronic hepatitis B is associated with an increased risk of B－cell non－Hodgkin's lymphoma and multiple myeloma[J]. Aliment Pharmacol Ther, 2019, 49( 5): 589－ 598. DOI: 10.1111/apt.15132.
[7]	REN W, WANG X, YANG M, et al. Distinct clinical and genetic features of hepatitis B virus－associated follicular lymphoma in Chinese patients[J]. Blood Adv, 2022, 6( 9): 2731－ 2744. DOI: 10.1182/bloodadvances.2021006410.
[8]	SCHARF RE. Thrombocytopenia and hemostatic changes in acute and chronic liver disease: pathophysiology, clinical and laboratory features, and management[J]. J Clin Med, 2021, 10( 7): 1530. DOI: 10.3390/jcm10071530.
[9]	JIANG H, LI Y, SHENG Q, et al. Relationship between Hepatitis B virus infection and platelet production and dysfunction[J]. Platelets, 2022, 33( 2): 212－ 218. DOI: 10.1080/09537104.2021.2002836.
[10]	ZELDIS JB, MUGISHIMA H, STEINBERG HN, et al. In vitro hepatitis B virus infection of human bone marrow cells[J]. J Clin Invest, 1986, 78( 2): 411－ 417. DOI: 10.1172/JCI112591.
[11]	HUANG Y, YAN Q, FAN R, et al. Hepatitis B virus replication in CD34⁺ hematopoietic stem cells from umbilical cord blood[J]. Med Sci Monit, 2016, 22: 1673－ 1681. DOI: 10.12659/msm.898680.
[12]	CHAI T, PRIOR S, COOKSLEY WG, et al. Infection of human bone marrow stromal cells by hepatitis B virus: implications for viral persistence and the suppression of hematopoiesis[J]. J Infect Dis, 1994, 169( 4): 871－ 874. DOI: 10.1093/infdis/169.4.871.
[13]	TERAZ－OROSZ A, COOPER N, CRAWLEY J, et al. Detection of anti－platelet antibodies in immune thrombocytopenia by flow cytometry[J]. Br J Haematol, 2019, 184( 5): 844－ 847. DOI: 10.1111/bjh.15187.
[14]	HUH HJ, PARK CJ, KIM SW, et al. Flow cytometric detection of platelet－associated immunoglobulin in patients with immune thrombocytopenic purpura and nonimmune thrombocytopenia[J]. Ann Clin Lab Sci, 2009, 39( 3): 283－ 288.
[15]	CHEN Y, HU J, CHEN Y. Platelet desialylation and TFH cells－the novel pathway of immune thrombocytopenia[J]. Exp Hematol Oncol, 2021, 10( 1): 21. DOI: 10.1186/s40164－021－00214－5.
[16]	VRBENSKY JR, NAZY I, CLARE R, et al. T cell－mediated autoimmunity in immune thrombocytopenia[J]. Eur J Haematol, 2022, 108( 1): 18－ 27. DOI: 10.1111/ejh.13705.
[17]	WANG H, LUO H, WAN X, et al. TNF－α/IFN－γ profile of HBV－specific CD4 T cells is associated with liver damage and viral clearance in chronic HBV infection[J]. J Hepatol, 2020, 72( 1): 45－ 56. DOI: 10.1016/j.jhep.2019.08.024.
[18]	ISMAIL AM, HIGAZI AM, NOMEIR HM, et al. IL－23/Th17 pathway and IL－17A gene polymorphism in Egyptian children with immune thrombocbytopenic purpura[J]. Ital J Pediatr, 2021, 47( 1): 178. DOI: 10.1186/s13052－021－01131－3.
[19]	LI Q, LIU Y, WANG X, et al. Regulation of Th1/Th2 and Th17/Treg by pDC/mDC imbalance in primary immune thrombocytopenia[J]. Exp Biol Med(Maywood), 2021, 246( 15): 1688－ 1697. DOI: 10.1177/15353702211009787.
[20]	ZHANG JY, ZHANG Z, LIN F, et al. Interleukin－17－producing CD4(+) T cells increase with severity of liver damage in patients with chronic hepatitis B[J]. Hepatology, 2010, 51( 1): 81－ 91. DOI: 10.1002/hep.23273.
[21]	KHANAM A, CHUA JV, KOTTILIL S. Immunopathology of chronic hepatitis B infection: Role of Innate and adaptive immune response in disease progression[J]. Int J Mol Sci, 2021, 22( 11): 5497. DOI: 10.3390/ijms22115497.
[22]	SHIN JS, SUBHAN MO, CAMBRIDGE G, et al. Alterations in B－and circulating T－follicular helper cell subsets in immune thrombotic thrombocytopenic purpura[J]. Blood Adv, 2022, 6( 12): 3792－ 3802. DOI: 10.1182/bloodadvances.2022007025.
[23]	WU X, SU Z, CAI B, et al. Increased circulating follicular regulatory T－like cells may play a critical role in chronic hepatitis B virus infection and disease progression[J]. Viral Immunol, 2018, 31( 5): 379－ 388. DOI: 10.1089/vim.2017.0171.
[24]	VYAS AK, LSLAM M, GARG G, et al. Humoral immune responses and hepatitis B infection[J]. Dig Dis, 2021, 39( 5): 516－ 525. DOI: 10.1159/000514274.
[25]	PROVAN D, SEMPLE JW. Recent advances in the mechanisms and treatment of immune thrombocytopenia[J]. EBioMedicine, 2022, 76: 103820. DOI: 10.1016/j.ebiom.2022.103820.
[26]	MÖCKEL T, BASTA F, WEINMANN－MENKE J, et al. B cell activating factor(BAFF): Structure, functions, autoimmunity and clinical implications in Systemic Lupus Erythematosus(SLE)[J]. Autoimmun Rev, 2021, 20( 2): 102736. DOI: 10.1016/j.autrev.2020.102736.
[27]	WANG Y, JIA X, ZHOU L, et al. Increased let－7b－5p is associated with enhanced BAFF－R expression and B cell survival in immune thrombocytopenia[J]. Int Immunopharmacol, 2021, 93: 107393. DOI: 10.1016/j.intimp.2021.107393.
[28]	YANG C, LI N, WANG Y, et al. Serum levels of B－cell activating factor in chronic hepatitis B virus infection: association with clinical diseases[J]. J Interferon Cytokine Res, 2014, 34( 10): 787－ 794. DOI: 10.1089/jir.2014.0032.
[29]	LU B, ZHANG B, WANG L, et al. Hepatitis B virus e antigen regulates monocyte function and promotes B lymphocyte activation[J]. Viral Immunol, 2017, 30( 1): 35－ 44. DOI: 10.1089/vim.2016.0113.
[30]	LIU H, OUYANG X, LI Y, et al. Involvement of levels of Toll like receptor－4 in monocytes, CD4⁺ T－lymphocyte subsets, and cytokines in patients with immune thrombocytopenic purpura[J]. Thromb Res, 2013, 132( 2): 196－ 201. DOI: 10.1016/j.thromres.2013.04.025.
[31]	LI Y, YIN S, CHEN Y, et al. Hepatitis B virus－induced hyperactivation of B cells in chronic hepatitis B patients via TLR4[J]. J Cell Mol Med, 2020, 24( 11): 6096－ 6106. DOI: 10.1111/jcmm.15202.
[32]	LI H, GUAN Y, SUN B, et al. Role of bone marrow－derived mesenchymal stem cell defects in CD8⁺ CD28^－ suppressor T－lymphocyte induction in patients with immune thrombocytopenia and associated mechanisms[J]. Br J Haematol, 2020, 191( 5): 852－ 862. DOI: 10.1111/bjh.16953.
[33]	WEI KP, PAN XN, XU ZJ, et al. Effect of hepatitis B virus on proliferation of human bone marrow mesenchymal stem cells in vitro[J/CD]. Chin J Exp Clin Infect Dis(Electronic Edition), 2013( 3): 395－ 398. DOI: 10.3877/cma.j.issn.1674－1358.2013.03.016. 魏开鹏, 潘兴南, 许正锯, 等. HBV对人骨髓间充质干细胞体外增殖的影响[J/CD]. 中华实验和临床感染病杂志(电子版), 2013( 3): 395－ 398. DOI: 10.3877/cma.j.issn.1674－1358.2013.03.016.
[34]	ZHU F, ZHOU ZH, XUE HY, et al. Clinical study of hepatitis B virus infection and immune thrombocytopenia[J]. J Clin Hematol, 2020, 33( 9): 630－ 633. DOI: 10.13201/j.issn.1004－2806.2020.09.009. 竺枫, 周忠豪, 薛宏怡, 等. 乙肝病毒感染与免疫性血小板减少症的临床研究[J]. 临床血液学杂志, 2020, 33( 9): 630－ 633. DOI: 10.13201/j.issn.1004－2806.2020.09.009.
[35]	XU D. Correlation between viral hepatitis and primary immune thrombocytopenia[J]. J Beihua Univ(Natural Science), 2019, 20( 6): 768－ 770. DOI: 10.11713/j.issn.1009－4822.2019.06.015. 徐丹. 病毒性肝炎与原发免疫性血小板减少症的相关性研究[J]. 北华大学学报(自然科学版), 2019, 20( 6): 768－ 770. DOI: 10.11713/j.issn.1009－4822.2019.06.015.
[36]	WANG L, LI L, LI C, et al. Significance of anti－HBc serological status in primary immune thrombocytopenia[J]. Br J Haematol, 2022, 196( 4): 1086－ 1095. DOI: 10.1111/bjh.17977.
[37]	SHI Y, ZHENG M. Hepatitis B virus persistence and reactivation[J]. BMJ, 2020, 370: m2200. DOI: 10.1136/bmj.m2200.
[38]	HUANG SC, YANG HC, KAO JH. Hepatitis B reactivation: diagnosis and management[J]. Expert Rev Gastroenterol Hepatol, 2020, 14( 7): 565－ 578. DOI: 10.1080/17474124.2020.1774364.
[39]	HE Q, SONG X, HUANG Y, et al. Dexamethasone stimulates hepatitis B virus(HBV) replication through autophagy[J]. Med Sci Monit, 2018, 24: 4617－ 4624. DOI: 10.12659/MSM.906250.
[40]	SCHUTGENS R. First－line therapy for immune thrombocytopenia: Time for change[J]. Hemasphere, 2022, 6( 10): e783. DOI: 10.1097/HS9.0000000000000783.
[41]	NEUNERT C, TERRELL DR, ARNOLD DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia[J]. Blood Adv, 2019, 3( 23): 3829－ 3866. DOI: 10.1182/bloodadvances.2019000966.
[42]	MARKHAM A. Avatrombopag: A review in thrombocytopenia[J]. Drugs, 2021, 81( 16): 1905－ 1913. DOI: 10.1007/s40265－021－01613－y.
[43]	CHEN YF, HUANG YT, LAI YH, et al. Efficacy and safety of eltrombopag in the treatment of chronic hepatitis B virus infection patients with thrombocytopenia(HBV－TP): A prospecitive, multi－center, single arm, phase II trail[C]. European Hematology Association, 2022: 2868.