Abdelwahed Ahmed H, Heineman Brent D, Wu George Y
Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA.
J Clin Transl Hepatol. 2023 Dec 28;11(7):1485-1497. doi: 10.14218/JCTH.2023.00067. Epub 2023 Sep 19.
Hepatitis B virus (HBV) is a widely prevalent liver infection that can cause acute or chronic hepatitis. Although current treatment modalities are highly effective in the suppression of viral levels, they cannot eliminate the virus or achieve definitive cure. This is a consequence of the complex nature of HBV-host interactions. Major challenges to achieving sustained viral suppression include the presence of a high viral burden from the HBV DNA and hepatitis B surface antigen (HBsAg), the presence of reservoirs for HBV replication and antigen production, and the HBV-impaired innate and adaptive immune response of the host. Those therapeutic methods include cell entry inhibitors, HBsAg inhibitors, gene editing approaches, immune-targeting therapies and direct inhibitors of covalently closed circular DNA (cccDNA). Novel approaches that target these key mechanisms are now being studied in preclinical and clinical phases. In this review article, we provide a comprehensive review on mechanisms by which HBV escapes elimination from current treatments, and highlight new agents to achieve a definitive HBV cure.
乙型肝炎病毒（HBV）是一种广泛流行的肝脏感染病毒，可导致急性或慢性肝炎。尽管目前的治疗方法在抑制病毒水平方面非常有效，但它们无法消除病毒或实现彻底治愈。这是HBV与宿主相互作用的复杂性质所导致的结果。实现持续病毒抑制的主要挑战包括来自HBV DNA和乙型肝炎表面抗原（HBsAg）的高病毒载量的存在、HBV复制和抗原产生的储存库的存在，以及宿主的HBV受损的固有和适应性免疫反应。这些治疗方法包括细胞进入抑制剂、HBsAg抑制剂、基因编辑方法、免疫靶向疗法和共价闭合环状DNA（cccDNA）的直接抑制剂。针对这些关键机制的新方法目前正在临床前和临床阶段进行研究。在这篇综述文章中，我们对HBV逃避当前治疗消除的机制进行了全面综述，并强调了实现彻底治愈HBV的新药物。
