从HBV特异性免疫细胞角度谈慢性乙型肝炎功能性治愈

刘小菊; 张政

doi:10.3969/j.issn.1001-5256.2020.05.004

从HBV特异性免疫细胞角度谈慢性乙型肝炎功能性治愈

DOI: 10.3969/j.issn.1001-5256.2020.05.004

刘小菊,
张政

1. 国家感染性疾病临床医学研究中心(深圳市第三人民医院)
2. 南方医科大学南方医院感染科

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出版历程
- 出版日期: 2020-05-20

Functional cure of chronic hepatitis B from the perspective of specific immune cells for hepatitis B virus

National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen, Guangdong 518112, China

摘要

摘要:
慢性乙型肝炎(CHB)患者实现功能性治愈代表患者获得了持久的病毒学抑制和免疫学控制,是目前国内外最新CHB防治指南推荐的理想治疗目标。CHB患者长期直接抗病毒治疗可获得病毒学抑制,但仅有极少数患者能获得功能性治愈,提示迫切需要抗病毒药物和免疫治疗的联合疗法。目前最佳治疗策略是靶向精准清除HBV感染的肝细胞,减少肝组织损伤;但这依赖于肝脏中HBV特异性免疫细胞。因此恢复或增强HBV特异性T淋巴细胞和B淋巴细胞的功能是实现CHB功能治愈的关键策略。
- 乙型肝炎病毒 /
- 乙型肝炎,慢性 /
- HBV特异性T淋巴细胞 /
- HBV特异性B淋巴细胞
Abstract:
Functional cure of chronic hepatitis B(CHB) marks sustained virological inhibition and immunological control and is the ideal treatment goal recommended by the latest guidelines for the prevention and treatment of CHB in China and foreign countries. CHB patients can achieve virological inhibition with the help of long-term direct antiviral therapy, and only a small number of patients can achieve functional cure, suggesting that there is an urgent need for the combination of direct antiviral therapy and immunotherapy. At present, the best treatment strategy is targeted precise clearance of HBV-infected hepatocytes to reduce liver injury, which depends on HBV-specific immune cells in the liver. Therefore, restoring or enhancing the function of HBV-specific T cells and B cells is the key strategy for functional cure of CHB.
- hepatitis B virus /
- hepatitis B,chronic /
- HBV-specific T cells /
- HBV-specific B cells

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参考文献(21)

[1] COOKE GS, ANDRIEUX-MEYER I, APPLEGATE TL, et al.Accelerating the elimination of viral hepatitis:A Lancet Gastroenterology&Hepatology Commission[J]. Lancet Gastroenterol Hepatol, 2019, 4(2):135-184.

[2] Chinese Society of Infectious Disease, Chinese Society of Hepatology, Chinese Medical Association. The expert consensus on functional cure of chronic hepatitis B[J]. J Clin Hepatol, 2019, 35(8):1693-1701.(in Chinese）中华医学会感染病学分会，中华医学会肝病学分会．慢性乙型肝炎临床治愈（功能性治愈）专家共识[J]．临床肝胆病杂志，2019, 35(8):1693-1701.

[3] 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.(in Chinese）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.

[4] XIA Y, LIANG TJ. Development of direct-acting antiviral and host-targeting agents for treatment of hepatitis B virus infection[J]. Gastroenterology, 2019, 156(2):311-324.

[5] SAEIDI A, ZANDI K, CHEOK YY, et al. T-cell exhaustion in chronic infections:Reversing the state of exhaustion and reinvigorating optimal protective immune responses[J]. Front Immunol, 2018, 9:2569.

[6] BURTON AR, PALLETT LJ, MCCOY LE, et al. Circulating and intrahepatic antiviral B cells are defective in hepatitis B[J]. J Clin Invest, 2018, 128(10):4588-4603.

[7] SALIMZADEH L, LE BERT N, DUTERTRE CA, et al. PD-1blockade partially recovers dysfunctional virus-specific B cells in chronic hepatitis B infection[J]. J Clin Invest, 2018,128(10):4573-4587.

[8] MAINI MK, BONI C, LEE CK, et al. The role of virus-specific CD8(+)cells in liver damage and viral control during persistent hepatitis B virus infection[J]. J Exp Med, 2000, 191(8):1269-1280.

[9] PARK JJ, WONG DK, WAHED AS, et al. Hepatitis B virusspecific and global T-cell dysfunction in chronic hepatitis B[J]. Gastroenterology, 2016, 150(3):684-695.

[10] TAN A, KOH S, BERTOLETTI A. Immune response in hepatitis B virus infection[J]. Cold Spring Harb Perspect Med, 2015,5(8):a021428.

[11] SCHUCH A, SALIMI ALIZEI E, HEIM K, et al. Phenotypic and functional differences of HBV core-specific versus HBV polymerase-specific CD8+T cells in chronically HBV-infected patients with low viral load[J]. Gut, 2019, 68(5):905-915.

[12] HOOGEVEEN RC, ROBIDOUX MP, SCHWARZ T, et al. Phenotype and function of HBV-specific T cells is determined by the targeted epitope in addition to the stage of infection[J].Gut, 2019, 68(5):893-904.

[13] SCHURICH A, PALLETT LJ, LUBOWIECKI M, et al. The third signal cytokine IL-12 rescues the anti-viral function of exhausted HBV-specific CD8 T cells[J]. PLoS Pathog, 2013,9(3):e1003208.

[14] TANG L, CHEN C, GAO X, et al. Interleukin 21 reinvigorates the antiviral activity of hepatitis B virus(HBV)-specific CD8+T cells in chronic HBV infection[J]. J Infect Dis, 2019, 219(5):750-759.

[15] RINKER F, ZIMMER CL, HÖNER ZU SIEDERDISSEN C, et al.Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B[J]. J Hepatol, 2018, 69(3):584-593.

[16] RIVINO L, LE BERT N, GILL US, et al. Hepatitis B virus-specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation[J]. J Clin Invest, 2018, 128(2):668-681.

[17] SCHURICH A, PALLETT LJ, JAJBHAY D, et al. Distinct metabolic requirements of exhausted and functional virus-specific CD8 T cells in the same host[J]. Cell Rep, 2016, 16(5):1243-1252.

[18] ZHANG S, ZHAO J, ZHANG Z. Humoral immunity, the underestimated player in hepatitis B[J]. Cell Mol Immunol, 2018,15(6):645-648.

[19] NEUMANN-HAEFELIN C, THIMME R. Entering the spotlight:Hepatitis B surface antigen-specific B cells[J]. J Clin Invest, 2018, 128(10):4257-4259.

[20] LE BERT N, SALIMZADEH L, GILL US, et al. Comparative characterization of B cells specific for HBV nucleocapsid and envelope proteins in patients with chronic hepatitis B[J]. J Hepatol, 2020, 72(1):34-44.

[21] CHEN Z, DIAZ G, POLLICINO T, et al. Role of humoral immunity against hepatitis B virus core antigen in the pathogenesis of acute liver failure[J]. Proc Natl Acad Sci U S A, 2018, 115(48):e11369-e11378.

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