Hepatitis B Virus-Specific T Cells as a Biomarker for Discontinuation of Nucleos(t)ide Analogue Therapy for Chronic Hepatitis B.
Hepatitis B Virus-Specific T Cells as a Biomarker for Discontinuation of Nucleos(t)ide Analogue Therapy for Chronic Hepatitis B.
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丙型肝炎病毒特异性T细胞作为慢性乙型肝炎的核（T）IDE模拟治疗中停用的生物标志物。
DOI：
10.1002/hep.30243
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
James Ou JH
中科院分区：
文献类型：
--
作者：
Tian Y;James Ou JH
乙型肝炎病毒（HBV）可引起严重的肝脏疾病，是一个主要的健康问题。全世界约有2.5亿人慢性感染。核苷类似物（NUCs），包括拉米夫定、阿德福韦、恩替卡韦、替诺福韦和替比夫定，是治疗慢性乙型肝炎（CHB）患者最常用的药物。NUCs可以有效地抑制HBV- dna复制，降低病毒载量，导致HBV e抗原（HBeAg）的丢失，HBeAg抗体的出现，以及丙氨酸转氨酶（ALT）水平的正常化。然而，它们不能靶向感染肝细胞中的HBV基因组DNA，也称为共价闭合环状DNA。因此，停用NUC治疗可导致病毒反弹和肝耀斑的发展，慢性乙型肝炎患者通常需要终生使用这种治疗。然而，也有一些患者可以安全地停止使用NUCs治疗。不幸的是，目前缺乏识别这类患者的生物标志物。最近，Rivino等人发现，在成功停止NUC治疗而未发生肝耀斑的慢性HBV患者中，程序性死亡1 (PD1)+ HBV特异性T细胞的数量远高于发生肝耀斑的患者。(1)他们的发现表明，PD1+ hbv特异性T细胞可能作为CHB患者安全停止NUC治疗急需的生物标志物。由于潜在的药物毒性、耐药突变体的出现或其他原因，一些慢性乙型肝炎患者可能不得不停止NUC治疗。这种治疗的终止有病毒反弹和肝耀斑发展的风险。(2) 2016年美国肝病研究协会（American Association for The Study of Liver Diseases）发布的指南指出，NUC治疗的最佳终点是HBV表面抗原（HBsAg）的丧失。然而，这种HBsAg的损失很少实现。(3)因此，迫切需要替代生物标志物来安全停止NUC治疗。
Hepatitis B virus (HBV) can cause severe liver diseases and is a major health problem. It chronically infects approximately 250 million people worldwide. Nucleos (t) ide analogs (NUCs), including lamivudine, adefovir, entecavir, tenofovir, and telbivudine, are the most frequently used drugs for treating chronic hepatitis B (CHB) patients. NUCs can efficiently suppress HBV-DNA replication and reduce viral load, leading to loss of the HBV e antigen (HBeAg), appearance of antibodies against HBeAg, and normalization of alanine aminotransferase (ALT) level. However, they cannot target HBV genomic DNA, also known as covalently closed circular DNA, in infected hepatocytes. For that reason, discontinuation of NUC therapy can lead to viral rebound and development of hepatic flares, and a lifelong treatment of this therapy is often required for CHB patients. Nevertheless, there are also some patients for whom treatment with NUCs can be safely stopped. Unfortunately, the biomarkers for identification of this subset of patients are currently lacking. Recently, Rivino et al. found that the population of programmed death 1 (PD1)+ HBV-specific T cells was much higher in chronic HBV patients who successfully discontinued NUC therapy without developing hepatic flares than in those patients who developed hepatic flares.(1) Their finding indicated that PD1+ HBV-specific T cells might serve as the much-needed biomarker for safe discontinuation of NUC therapy for CHB patients. Because of potential drug toxicity, emergence of drug-resistant mutants, or other reasons, NUC therapy may have to be stopped for some CHB patients. This termination of treatment poses a risk of viral rebound and development of hepatic flares.(2) The guidelines published by the American Association for the Study of Liver Diseases in 2016 indicate that the best endpoint of NUC therapy is loss of HBV surface antigen (HBsAg). However, this loss of HBsAg is infrequently achieved.(3) Thus, there is a strong need for alternative biomarkers for safe stopping of NUC therapy.
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DOI：
10.1084/jem.20142237
发表时间：
2015-06-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Odorizzi PM;Pauken KE;Paley MA;Sharpe A;Wherry EJ
通讯作者：
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影响因子：
32.4
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作者：
Chi, Heng;Li, Zhandong;Peng, Jie
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