Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Aliment Pharmacol Ther. 2022 Apr;55(7):805-819. doi: 10.1111/apt.16828. Epub 2022 Feb 27.
The hepatitis B virus (HBV) affects an estimated 290 million individuals worldwide and is responsible for approximately 900 000 deaths annually, mostly from complications of cirrhosis and hepatocellular carcinoma. Although current treatment is effective at preventing complications of chronic hepatitis B, it is not curative, and often must be administered long term. There is a need for safe, effective, finite duration curative therapy.
Our aim was to provide a concise, up to date review of all currently available and emerging treatment options for chronic hepatitis B.
We conducted a search of PubMed, clinicaltrials.gov, major meeting abstracts and pharmaceutical websites for publications and communications on current and emerging therapies for HBV.
Currently approved treatment options for chronic hepatitis B include peginterferon alpha-2a and nucleos(t)ide analogues. Both options do not offer a 'complete cure' (clearance of covalently closed circular DNA (cccDNA) and integrated HBV DNA) and rarely achieve a 'functional cure' (hepatitis B surface antigen (HBsAg) loss). An improved understanding of the viral lifecycle, immunopathogenesis and recent advances in drug delivery technologies have led to many novel therapeutic approaches that are currently being evaluated in clinical trials including targeting of viral entry, cccDNA, viral transcription, core protein, and release of HBsAg and HBV polymerase. Additionally, novel immunological approaches that include targeting the innate and adaptive immune system and therapeutic vaccination are being pursued.
The breadth and scope of novel therapies in development hold promise for regimen/s that will achieve functional cure.
全球估计有 2.9 亿人感染乙型肝炎病毒(HBV),每年约有 90 万人因此死亡,主要死于肝硬化和肝细胞癌等并发症。虽然目前的治疗方法能有效预防慢性乙型肝炎的并发症,但无法治愈,且通常需要长期治疗。因此,我们需要一种安全、有效、疗程有限的治愈性疗法。
我们旨在提供一份简明、最新的关于慢性乙型肝炎所有现有和新兴治疗方案的综述。
我们检索了 PubMed、clinicaltrials.gov、主要会议摘要和制药公司网站,以获取有关 HBV 现有和新兴疗法的出版物和交流信息。
目前批准的慢性乙型肝炎治疗方案包括聚乙二醇干扰素 α-2a 和核苷(酸)类似物。这两种方案都不能实现“完全治愈”(即共价闭合环状 DNA(cccDNA)和整合 HBV DNA 的清除),也很少能实现“功能性治愈”(即乙型肝炎表面抗原(HBsAg)的丢失)。对病毒生命周期、免疫发病机制的深入理解以及药物输送技术的最新进展,促使了许多新的治疗方法的出现,这些方法目前正在临床试验中进行评估,包括针对病毒进入、cccDNA、病毒转录、核心蛋白以及 HBsAg 和 HBV 聚合酶的释放等方面的治疗。此外,还在探索新的免疫治疗方法,包括针对固有和适应性免疫系统的治疗性疫苗。
新型治疗方法的多样性和范围为实现功能性治愈的方案带来了希望。