乙型肝炎病毒新型治疗方式的研究进展

Research progress of new treatments for hepatitis B virus

乙型肝炎病毒(hepatitis B virus,HBV)感染可以导致严重的肝脏疾病,是肝纤维化、肝细胞癌(hepatocellular carcinoma,HCC)病死率高的主要原因。尽管已经拥有有效的疫苗,但三联乙肝疫苗的全球覆盖率为84%,未达100%,现有感染人数与新增人数仍然很多。目前主要的抗HBV药物为核苷/核苷酸类似物(nucleotide analogues,NAs)以及干扰素(interferon,IFN)。但二者对病毒持续存在的根本因素——共价、闭合、环状DNA分子(covalently closed circular DNA,cccDNA)无效,故现有的抗病毒药物并不能彻底治愈HBV感染。HBV的新型治疗方法可以通过靶向cccDNA而使其失效,为治愈慢性HBV感染带来了希望。文章对当前新型治疗方法中研究较多的RNA干扰、基因编辑和表观遗传修饰方法在治疗HBV感染中的作用和新发展进行概述。

Hepatitis B virus(HBV)infection can cause severe liver disease,which is the main reason for the high mortality of liver fibrosis and hepatocellular carcinoma(HCC).Despite the availability of effective vaccines,the global coverage rate of the triple hepatitis B vaccine is 84%,which has not reached 100%.There are still a large number of existing infections and new infections.At present,the major anti-HBV drugs are nucleoside/nucleotide analogs(NAs)and interferons(IFN).However,the two types of drugs are ineffective against covalent,closed,and circular DNA molecules(cccDNA),which is the fundamental factor for the continued persistence of the virus.Therefore,existing antiviral drugs are incapable to achieve a completely cure of HBV infection.The new therapy can make it ineffective by target cccDNA,which brings hope for curing chronic HBV infection.This review summarized the role and new development of RNA interference,gene editing and epigenetic modification in the treatment of HBV infection.