慢性乙型肝炎临床治愈研究进展

Progress on clinical cure of chronic hepatitis B

慢性乙型肝炎病毒(hepatitis B virus,HBV)感染严重威胁人类健康。探讨慢性乙型肝炎(chronic hepatitis B,CHB)抗病毒治疗方案可使更多患者临床获益。核苷(酸)类似物[nucleos(t)ide analogues,NAs]及干扰素类(interferon,IFN)为目前主要的抗病毒药物,CHB患者经规范治疗可有效抑制病毒复制、控制疾病进展。但这两类药物均无法直接作用于肝细胞内的cccDNA,CHB难以实现彻底治愈。目前部分合适的CHB患者可追求临床治愈(持续病毒学应答且HBsAg阴转或伴有抗-HBs阳转、ALT正常、肝组织病变轻微或无病变)。无论是IFN还是NAs,单一用药方案很难达到临床治愈,新型抗HBV物开多处于临床前期,目前现有抗病毒治疗方案的优化是临床研究关注的问题。NAs经治患者联合或序贯IFN治疗可提高病毒学应答率及HBeAg血清学转换率,使更多患者实现临床治愈。影响HBsAg清除的因素较多,筛选有利于获得临床治愈患者的特征及制定个体化治疗方案仍需深入研究。

Chronic hepatitis B virus(HBV)is a serious threat to human health.It is still necessary to explore the antiviral treatment for chronic hepatitis B(CHB)to benefit more patients.Nucleos(t)ide analogue(NAs)and interferon(IFN)are the main antiviral drugs.Standardized treatment for patients with CHB can effectively inhibit viral replication and control the progress of the disease.However,these two drugs cannot directly affect cccDNA in liver cells,and it is difficult to cure CHB completely.Some suitable patients with CHB can pursue clinical cure(continuous virological response and HBsAg eliminated or accompanied by anti-HBs positive,normal ALT,slight or no inflammation of liver tissue).Whether IFN or NAs,single drug therapy is difficult to achieve clinical cure.Most new anti-hepatitis B virus drugs are in the pre-clinical stage,which is not available.Currently,the optimization of the existing antiviral treatment scheme is a concern of various clinical studies.In the current treatment strategies,NAs treated patients with sequential or combining IFN may improve the virological response rates and HBeAg serological conversion rate,which can make more patients achieve clinical cure.It has been found that there are many factors influencing HBsAg clearance.It is necessary to furtherly study the characteristics of patients who are promising to clinical cure and to formulate individualized treatment plans.