Fung James, Lai Ching-Lung, Seto Wai-Kay, Yuen Man-Fung
a Division of Gastroenterology and Hepatology, Department of Medicine , The University of Hong Kong , Hong Kong SAR.
b State Key Laboratory for Liver Research , The University of Hong Kong , Hong Kong SAR.
Expert Opin Emerg Drugs. 2016 Jun;21(2):183-93. doi: 10.1517/14728214.2016.1162155. Epub 2016 Mar 22.
Nucleos(t)ide analogs and interferon-based compounds are currently approved for the treatment of chronic hepatitis B (CHB). Although these treatments are effective in suppressing viral replication, it is unable to completely eradicate the virus from the host. Therefore, CHB patients are at a life-long risk of developing complications, including hepatocellular carcinoma.
Drugs targeting novel sites of the hepatitis B virus (HBV) replication cycle and the host immune response in development are discussed. As current available drugs only target a small segment of the HBV life cycle, the development of new agents targeting different sites is an important step in eradicating HBV. The host immunological response is also vital in viral clearance. Newer agents in development include immunomodulatory agents and therapeutic vaccines.
For any chance of eradication, a combination of drugs targeting both the host factors and different sites of the viral life cycle will be required. Two key components to achieving this goal include the removal of covalently closed circular DNA (cccDNA) together with restoration of the immune control against HBV.
核苷（酸）类似物和基于干扰素的化合物目前已被批准用于治疗慢性乙型肝炎（CHB）。尽管这些治疗方法在抑制病毒复制方面有效，但无法将病毒从宿主体内完全清除。因此，CHB患者终生都有发生并发症的风险，包括肝细胞癌。
讨论了正在研发的针对乙型肝炎病毒（HBV）复制周期新位点和宿主免疫反应的药物。由于目前可用的药物仅针对HBV生命周期的一小部分，开发针对不同位点的新药物是根除HBV的重要一步。宿主免疫反应在病毒清除中也至关重要。正在研发的新型药物包括免疫调节剂和治疗性疫苗。
为了有根除的机会，需要联合使用针对宿主因素和病毒生命周期不同位点的药物。实现这一目标的两个关键要素包括去除共价闭合环状DNA（cccDNA）以及恢复针对HBV的免疫控制。
