HCV感染者抗病毒治疗前后免疫状态的变化

蒋莹莹; 张晓慧; 郑素军

doi:10.3969/j.issn.1001-5256.2018.02.041

HCV感染者抗病毒治疗前后免疫状态的变化

DOI: 10.3969/j.issn.1001-5256.2018.02.041

首都医科大学附属北京佑安医院疑难肝病及人工肝中心

基金项目:

北京市科学技术委员会资助临床特色项目(Z131107002213019,Z151100004015066)；国家自然科学基金(81500472)；

详细信息

中图分类号: R512.63
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出版历程
- 出版日期: 2018-02-20

Change in immune status after antiviral therapy in patients with hepatitis C virus infection

Intractable Hepatic Diseases and Artificial Liver Treatment & Training Center, Beijing YouAn Hospital, Capital Medical University

Research funding:

摘要

摘要:
HCV感染是全球性的公共问题。目前我国主要的抗HCV治疗方案是聚乙二醇干扰素联合利巴韦林,但是该方案的持续病毒学应答率并不理想;直接抗病毒药物（DAA）的出现,在治疗丙型肝炎患者中取得了显著的疗效。简述了抗HCV治疗前后机体免疫状态的变化情况,从固有免疫、适应性免疫以及细胞因子和趋化因子三个方面进行了介绍。分析表明,HCV患者机体的免疫调控十分复杂,不同的研究结果不尽相同。但是总体来看,经过抗病毒治疗后,NK细胞表面受体表达以及其功能有恢复的趋势,甚至可以恢复至正常化;IFN的治疗并不能恢复病毒特异性CD8+T淋巴细胞的功能,而DAA治疗前后细胞毒性T淋巴细胞的变化规律尚未阐明;DAA对细胞因子以及趋化因子的长期的影响仍需要进一步研究。
- 抗病毒药 /
- 肝炎,丙型 /
- 免疫 /
- 综述
Abstract:
Hepatitis C virus (HCV) infection is a global public health issue.At present, pegylated interferon (IFN) combined with ribavirin is the major therapeutic regimen for anti-HCV treatment in China, but this regimen cannot achieve ideal sustained virologic response.Direct-acting antivirals (DAA) have achieved marked clinical effects in the treatment of patients with hepatitis C.This article briefly describes the change in immune status after anti-HCV treatment from the three aspects of innate immunity, adaptive immunity, and cytokines/chemokines.The analysis shows that HCV patients have complex immunoregulation, and the results vary from one study to another.In general, the expression of NK cell surface receptor and its function tend to recover and may even recover to a normal state.IFN treatment cannot restore the function of virus-specific CD8+T lymphocytes, while the change in cytotoxic T lymphocytes after DAA treatment has not been clarified.Further studies are needed to elucidate the long-term effect of DAA on cytokines and chemokines.
- antiviral agents /
- hepatitis C /
- immunity /
- review

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参考文献(31)

[1]CHOO QL, KUO G, WEINER AJ, et al.Isolation of a c DNA clone derived from a blood-borne non-A, non-B viral hepatitis genome[J].Science, 1989, 244 (4902) :359-362.

[2]HOOFNAGLE JH.Course and outcome of hepatitis C[J].Hepatology, 2002, 36 (5 Suppl 1) :s21-s29.

[3]PIETSCHMANN T.Virology:Final entry key for hepatitis C[J].Nature, 2009, 457 (7231) :797-798.

[4]JIANG XQ, ZOU XJ, TIAN DY.Virological response of chronic hepatitis C treated with peg-interferon a-2a and ribavirin[J].J Clin Hepatol, 2011, 27 (4) :417-419. (in Chinese) 姜雪强, 邹小静, 田德英.聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎患者的病毒学应答[J].临床肝胆病杂志, 2011, 27 (4) :417-419.

[5]AFDHAL N, REDDY KR, NELSON DR, et al.Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection[J].N Engl J Med, 2014, 370 (16) :1483-1493.

[6]CHEENT K, KHAKOO SI.Natural killer cells and hepatitis C:action and reaction[J].Gut, 2011, 60 (2) :268-278.

[7]EDLICH B, AHLENSTIEL G, ZABALETA AZPIROZ A, et al.Early changes in interferon signaling define natural killer cell response and refractoriness to interferon-based therapy of hepatitis C patients[J].Hepatology, 2012, 55 (1) :39-48.

[8]SERTI E, CHEPA-LOTREA X, KIM YJ, et al.Successful interferon-free therapy of chronic hepatitis C virus infection normalizes natural killer cell function[J].Gastroenterology, 2015, 149 (1) :190-200.e192.

[9]SPAAN M, van OORD G, KREEFFT K, et al.Immunological analysis during interferon-free therapy for chronic hepatitis C virus infection reveals modulation of the natural killer cell compartment[J].J Infect Dis, 2016, 213 (2) :216-223.

[10] DUAN ZJ, ZHI YH, LONG L, et al.The frequency, phenotypes and invtiro cytotoxic effects of icrculating CD 56+T cells in the patients with chornic HCV infection[J].Chin J Microbiol Immunol, 2013, 33 (7) :481-487. (in Chinese) 段昭君, 支玉红, 龙璐, 等.慢性HCV感染者外周血中CD56+T细胞频数、表型和体外细胞毒功能研究[J].中华微生物学和免疫学杂志, 2013, 33 (7) :481-487.

[11]GOLDEN-MASON L, MADRIGAL-ESTEBAS L, MCGRATH E, et al.Altered natural killer cell subset distributions in resolved and persistent hepatitis C virus infection following single source exposure[J].Gut, 2008, 57 (8) :1121-1128.

[12]WANG JJ.Study on natural killer cell function in hepatitis C virus infection and antiviral therapy outcome[D].Wuhan:Huazhong University of Science and Technology, 2010.王久君.NK细胞功能与HCV感染及抗病毒治疗转归的研究[D].武汉:华中科技大学, 2010.

[13]HARRISON RJ, ETTORRE A, LITTLE AM, et al.Association of NKG2A with treatment for chronic hepatitis C virus infection[J].Clin Exp Immunol, 2010, 161 (2) :306-314.

[14]MERAD M, SATHE P, HELFT J, et al.The dendritic cell lineage:ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting[J].Annu Rev Immunol, 2013, 31:563-604.

[15]MENGSHOL JA, GOLDEN-MASON L, CASTELBLANCO N, et al.Impaired plasmacytoid dendritic cell maturation and differential chemotaxis in chronic hepatitis C virus:associations with antiviral treatment outcomes[J].Gut, 2009, 58 (7) :964-973.

[16]LIANG CC, LIU CH, LIN YL, et al.Functional impairment of dendritic cells in patients infected with hepatitis C virus genotype 1who failed peginterferon plus ribavirin therapy[J].J Med Virol, 2011, 83 (7) :1212-1220.

[17]HAMMOND T, LEE S, WATSON MW, et al.Decreased IFNgamma production correlates with diminished production of cytokines by dendritic cells in patients infected with hepatitis C virus and receiving therapy[J].J Viral Hepat, 2011, 18 (7) :482-492.

[18]KLENERMAN P, THIMME R.T cell responses in hepatitis C:the good, the bad and the unconventional[J].Gut, 2012, 61 (8) :1226-1234.

[19]SEIGEL B, BENGSCH B, LOHMANN V, et al.Factors that determine the antiviral efficacy of HCV-specific CD8 (+) T cells ex vivo[J].Gastroenterology, 2013, 144 (2) :426-436.

[20]MARTIN B, HENNECKE N, LOHMANN V, et al.Restoration of HCV-specific CD8+T cell function by interferon-free therapy[J].J Hepatol, 2014, 61 (3) :538-543.

[21]BARRETT L, SHIVASABESAN G, WANG C, et al.Altered HCV specific T cell immunity very early in interferon free HCV DAA therapy[J].J Hepatol, 2013, 58 (S1) :s1.

[22]BURCHILL MA, GOLDEN-MASON L, WIND-ROTOLO M, et al.Memory re-differentiation and reduced lymphocyte activation in chronic HCV-infected patients receiving direct-acting antivirals[J].J Viral Hepat, 2015, 22 (12) :983-991.

[23]SPAAN M, CLAASSEN MA, HOU J, et al.The intrahepatic T cell compartment does not normalize years after therapy-induced hepatitis C virus eradication[J].J Infect Dis, 2015, 212 (3) :386-390.

[24]LANGHANS B, NISCHALKE HD, KRAMER B, et al.Increased peripheral CD4+regulatory T cells persist after successful direct-acting antiviral treatment of chronic hepatitis C[J].J Hepatol, 2017, 66 (5) :888-896.

[25] REIG M, MARINO Z, PERELLO C, et al.Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy[J].J Hepatol, 2016, 65 (4) :719-726.

[26]GODFREY DI, ULDRICH AP, MCCLUSKEY J, et al.The burgeoning family of unconventional T cells[J].Nat Immunol, 2015, 16 (11) :1114-1123.

[27]FRANCISZKIEWICZ K, SALOU M, LEGOUX F, et al.MHC class I-related molecule, MRI, and mucosal-associated invariant T cells[J].Immunol Rev, 2016, 272 (1) :120-138.

[28]HOFMANN M, THIMME R.MAIT be different-persisting dysfunction after DAA-mediated clearance of chronic hepatitis C virus infection[J].Eur J Immunol, 2016, 46 (9) :2099-2102.

[29]CARLIN AF, ARISTIZABAL P, SONG Q, et al.Temporal dynamics of inflammatory cytokines/chemokines during sofosbuvir and ribavirin therapy for genotype 2 and 3 hepatitis C infection[J].Hepatology, 2015, 62 (4) :1047-1058.

[30]HENGST J, FALK CS, SCHLAPHOFF V, et al.Direct-acting antiviral-induced hepatitis C virus clearance does not completely restore the altered cytokine and chemokine milieu in patients with chronic hepatitis C[J].J Infect Dis, 2016, 214 (12) :1965-1974.

[31]REHERMANN B, BERTOLETTI A.Immunological aspects of antiviral therapy of chronic hepatitis B virus and hepatitis C virus infections[J].Hepatology, 2015, 61 (2) :712-721.

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