我们需要新颖的组合来治愈HBV感染吗？

StephenW

Liver Int. 2020 Feb;40 Suppl 1:35-42. doi: 10.1111/liv.14371.
Will we need novel combinations to cure HBV infection?
Dusheiko G1,2.
Author information

1
    Kings College Hospital, London, UK.
2
    University College London Medical School, London, UK.

Abstract

Chronic hepatitis B is a numerically important cause of cirrhosis and hepatocellular carcinoma. Nucleoside analogue therapy may modify the risk. However, maintenance suppressive therapy is required, as a functional cure (generally defined as loss of HBsAg off treatment) is an uncommon outcome of antiviral treatment. Chronic hepatitis B is a numerically important cause of cirrhosis and hepatocellular carcinoma. Nucleoside analogue therapy may modify the risk. However, maintenance suppressive therapy is required, as a functional cure (generally defined as loss of HBsAg off treatment) is an uncommon outcome of antiviral treatment. Currently numerous investigational agents being developed to either interfere with specific steps in HBV replication or as host cellular targeting agents, that inhibit viral replication, and deplete or inactivate cccDNA, or as immune modulators. Synergistic mechanisms will be needed to incorporate a decrease in HBV transcription, impairment of transcription from HBV genomes, loss of cccDNA or altered epigenetic regulation of cccDNA transcription, and immune modulation or immunologically stimulated hepatocyte cell turnover. Nucleoside analogue suppressed patients are being included in many current trials. Trials are progressing to combination therapy as additive or synergistic effects are sought. These trials will provide important insights into the biology of HBV and perturbations of the immune response, required to effect HBsAg loss at different stages of the disease. The prospect of cures of hepatitis B would ensure that a wide range of patients could be deemed candidates for treatment with new compounds if these were highly effective, finite and safe. Withdrawal of therapy in short-term trials is challenging because short-term therapies may risk severe hepatitis flares, and hepatic decompensation. The limited clinical trial data to date suggest that combination therapy is inevitable.

© 2020 The Authors. Liver International published by John Wiley & Sons Ltd.
KEYWORDS:

Hepatitis B; antiviral therapy; nucleoside analogues; treatment of hepatitis B; viral eradication

PMID:
    32077595
DOI:
    10.1111/liv.14371

StephenW

肝内科。 2020年2月； 40增刊1：35-42。 Doi：10.1111 / liv.14371。
我们需要新颖的组合来治愈HBV感染吗？
杜希科G1,2。
作者信息

1个
英国伦敦国王学院医院。
2
英国伦敦大学学院伦敦医学院。

抽象

慢性乙型肝炎是肝硬化和肝细胞癌的重要数字原因。核苷类似物治疗可能会改变风险。但是，需要维持抑制疗法，因为功能性治愈（通常定义为HBsAg脱落）是抗病毒治疗的罕见结果。慢性乙型肝炎是肝硬化和肝细胞癌的重要数字原因。核苷类似物治疗可能会改变风险。但是，需要维持抑制疗法，因为功能性治愈（通常定义为HBsAg脱落）是抗病毒治疗的罕见结果。当前，正在开发许多研究试剂以干扰HBV复制中的特定步骤或作为宿主细胞靶向剂，其抑制病毒复制并耗尽或灭活cccDNA，或作为免疫调节剂。将需要协同机制来整合HBV转录的减少，HBV基因组转录的损伤，cccDNA的丢失或cccDNA转录的表观遗传调控的改变以及免疫调节或免疫刺激的肝细胞更新。目前许多试验都包括核苷类似物抑制患者。随着寻求加和或协同作用，试验正在向组合疗法发展。这些试验将为了解在疾病的不同阶段影响HBsAg丧失所需的HBV生物学和免疫应答扰动提供重要见解。治愈乙肝的前景将确保，如果新化合物高效，有限且安全，则可以将其视为新化合物治疗的候选对象。在短期试验中退出治疗具有挑战性，因为短期治疗可能会导致严重的肝炎发作和肝代偿失调。迄今为止有限的临床试验数据表明联合治疗是不可避免的。

©2020作者。约翰·威利父子有限公司出版的《肝脏国际》
关键字：

乙型肝炎；抗病毒治疗；核苷类似物；乙型肝炎的治疗；病毒根除

PMID：
32077595
DOI：
10.1111 / liv.14371

StephenW

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/liv.14371