慢性乙型肝炎潜在治疗靶点和新药研发进展

Novel potential treatments for chronic hepatitis B virus infections

摘要:

尽管预防性疫苗显著减少了乙型肝炎病毒（hepatitis B virus，HBV）新发感染，但目前全球仍有超过2.4亿慢性HBV感染者，其中每年因HBV感染相关的终末肝病和肝癌引起的死亡人数高达68万。目前用于慢性乙型肝炎（chronic hepatitis B，CHB）治疗的抗病毒药物包括干扰素和核苷/核苷酸类似物两大类，但均难以实现理想的临床治疗终点，即乙肝表面抗原（HBsAg）阴转或血清学转换。针对CHB患者尚未被满足的巨大医疗需求，国内外团队正在针对HBV生活周期的各个关键步骤以及潜在的宿主因子，尝试研发更为有效的CHB治疗药物，本文简要综述了当前处于临床开发阶段以及部分临床前阶段的CHB候选药物研发进展。

Abstract:

Over 240 million people worldwide are chronically infected with hepatitis B virus (HBV) although the HBV prophylactic vaccine has dramatically reduced new infections. However, still up to 680000 deaths per year are caused by HBV-related end-stage liver diseases and liver cancer. Currently, strategies for the treatment of Chronic Hepatitis B (CHB) include interferon-alpha (IFNα) and nucleos(t)ide analogues (NAs), but it is difficult to achieve the ideal clinical treatment endpoint, namely hepatitis B surface antigen (HBsAg) negative or serological conversion. Many teams are trying to develop more effective treatments, targeting key steps in the HBV life cycle and potential host factors, aiming to great medical needs for CHB patients that have not yet been met. This article reviews the advances in the research and development of the potential drugs in clinical development and partial preclinical stages.