Department of Biology, Gilead Sciences, Foster City, California 94404, USA.
Semin Liver Dis. 2013 May;33(2):130-7. doi: 10.1055/s-0033-1345713. Epub 2013 Jun 8.
Chronic hepatitis B virus (CHB) is managed effectively with either nucleoside/nucleotide-based or interferon-based therapies. However, most patients receiving these therapies do not establish long-term, durable control of infection after treatment withdrawal. In particular, rates of hepatitis B surface-antigen loss and seroconversion to antisurface-antigen antibody are very low. Thus, novel therapies and treatment modalities are necessary to achieve either elimination of the virus from the liver or durable immune control of hepatitis B virus (HBV) infection in the absence of chronic therapy ("functional cure"). Here the authors review new targets and approaches for treating CHB. These approaches can be divided into two broad categories-those targeting the virus or host factors required by the virus and those targeting the innate or adaptive immune systems. Unfortunately, although a variety of promising strategies have been identified and several new approaches have achieved preclinical validation, relatively few novel drug candidates are in active clinical studies to treat CHB. Thus, functional cure of CHB infection remains an important therapeutic challenge.
慢性乙型肝炎病毒（CHB）可通过核苷（酸）类似物或干扰素治疗有效管理。然而，大多数接受这些治疗的患者在停药后无法长期、持久地控制感染。特别是乙型肝炎表面抗原（HBsAg）丢失和抗表面抗原抗体血清转换的发生率非常低。因此，需要新的治疗方法和治疗模式来实现病毒从肝脏中消除或在没有慢性治疗的情况下对乙型肝炎病毒（HBV）感染的持久免疫控制（“功能性治愈”）。作者在这里回顾了治疗 CHB 的新靶点和方法。这些方法可分为两大类：针对病毒或病毒所需的宿主因素的方法，以及针对先天或适应性免疫系统的方法。不幸的是，尽管已经确定了多种有前途的策略，并且几种新方法已经通过了临床前验证，但在积极进行治疗 CHB 的临床研究的新型药物候选物相对较少。因此，CHB 感染的功能性治愈仍然是一个重要的治疗挑战。
