Secretaria de Estado da Saúde-SES, Superintendência de Vigilância em Saúde-SUVISA/GO, Gerência de Vigilância Epidemiológica de Doenças Transmissíveis-GVEDT/Coordenação de Análises e Pesquisas-CAP, Goiânia, Goiás, Brazil.
Department of Microbiology, Laboratory of Human Virology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia, Goiás, Brazil.
Med Res Rev. 2024 Sep;44(5):2015-2034. doi: 10.1002/med.22030. Epub 2024 Mar 25.
The hepatitis B elimination is a goal proposed by the WHO to be achieved by 2030 through the adoption of synergistic measures for the prevention and chronic HBV infection treatment. Complete cure is characterized by the HBV elimination from the body and is the goal of the chronic hepatitis B treatment, which once achieved, will enable the hepatitis B elimination. This, today, has been a scientific challenge. The difficulty in achieving a complete cure is due to the indefinite maintenance of a covalently closed episomal circular DNA (cccDNA) reservoir and the maintenance and persistence of an insufficient and dysfunctional immune response in chronically infected patients. Among the measures adopted to eliminate hepatitis B, two have the potential to directly interfere with the virus cycle, but with limited effect on HBV control. These are conventional vaccines-blocking transmission and antiviral therapy-inhibiting replication. Vaccines, despite their effectiveness in protecting against horizontal transmission and preventing mother-to-child vertical transmission, have no effect on chronic infection or potential to eliminate the virus. Treatment with antivirals suppresses viral replication, but has no curative effect, as it has no action against cccDNA. Therapeutic vaccines comprise an additional approach in the chronic infection treatment, however, they have only a modest effect on the immune system, enhancing it temporarily. This manuscript aims to address (1) the cccDNA persistence in the hepatocyte nucleus and the immune response dysfunction in chronically infected individuals as two primary factors that have hampered the treatment and HBV elimination from the human body; (2) the limitations of antiviral therapy and therapeutic vaccines, as strategies to control hepatitis B; and (3) the possibly promising therapeutic approaches for the complete cure and elimination of hepatitis B.
乙型肝炎消除是世界卫生组织（WHO）提出的一个目标，旨在 2030 年之前通过采取协同措施来预防和治疗慢性乙型肝炎病毒（HBV）感染。完全治愈的特征是 HBV 从体内消除，这是慢性乙型肝炎治疗的目标，一旦实现，将能够消除乙型肝炎。目前，这是一个科学挑战。难以实现完全治愈的原因是共价闭合环状 DNA（cccDNA）库的持续存在以及慢性感染患者的免疫反应不足和功能障碍的持续存在。在消除乙型肝炎的措施中，有两种措施具有直接干扰病毒周期的潜力，但对 HBV 控制的效果有限。这些措施包括常规疫苗——阻断传播和抗病毒治疗——抑制复制。疫苗尽管在预防水平传播和母婴垂直传播方面有效，但对慢性感染或消除病毒的潜力没有影响。抗病毒治疗抑制病毒复制，但没有治愈效果，因为它对 cccDNA 没有作用。治疗性疫苗是慢性感染治疗的另一种方法，但对免疫系统的作用有限，只能暂时增强免疫系统。本文旨在探讨（1）cccDNA 在肝细胞核中的持续存在和慢性感染个体的免疫反应功能障碍，这是阻碍治疗和从人体中消除 HBV 的两个主要因素；（2）抗病毒治疗和治疗性疫苗作为控制乙型肝炎的策略的局限性；（3）可能有希望的完全治愈和消除乙型肝炎的治疗方法。
