慢性乙型肝炎抗病毒新药的临床研究  

Clinical studies of new antiviral drugs for chronic hepatitis B

作　　者：张洪[1] 朱晓雪[1] 买佳佳 陈红[1] 周景 胡月[1] 徐佳[1] 丁艳华[1] ZHANG Hong;ZHU Xiaoxue;MAI Jiajia;CHEN Hong;ZHOU Jing;HU Yue;XU Jia;DING Yanhua(Ward of Phase I Clinical Trial, The First Hospital of Jilin University, Changchun 130021, China)

机构地区：[1]吉林大学第一医院Ⅰ期临床试验病房,长春130021

出　　处：《临床肝胆病杂志》2021年第5期1006-1010,共5页Journal of Clinical Hepatology

基　　金：“十三五”新药重大专项(2018ZX09301007005)。

摘　　要：HBV感染是全球重大公共卫生问题。慢性乙型肝炎(CHB)临床治愈(亦称功能性治愈)是目前国内外最新CHB防治指南推荐的理想治疗目标。以直接抗病毒药物[如核苷(酸)类似物(NAs)]或免疫调节剂[如聚乙二醇化干扰素(PEG-IFN)α]序贯或联合治疗的优化方案治愈率都不高。CHB治疗药物的研发领域近年正处于快速发展阶段。综述了CHB抗病毒新药的临床研究,包括受试者的选择、研究设计、给药剂量、剂量爬坡、不良事件、疗效评价等关键环节。需要引入定量药理学知识来分析药物的体内暴露量与药效、不良反应的关系,以及纳入探索性指标进行分析。为抗HBV新药临床研发提供经验和新思路。Hepatitis B virus(HBV)infection is a major global public health issue.Clinical cure(also known as functional cure)of chronic hepatitis B(CHB)is the ideal therapeutic goal recommended by the latest guidelines for the prevention and treatment of CHB in China and globally.Optimized treatment regimens with direct-acting antiviral agents[e.g.,nucleos(t)ide analogues]or immunomodulators(e.g.,pegylated interferon-α)sequentially or in combination tend to have low cure rates.Rapid development has been achieved in the research and development of drugs for the treatment of CHB.This article reviews the clinical study of new antiviral drugs for CHB,including the selection of subjects,study design,dosage,dose escalation,adverse events,and efficacy evaluation.It is necessary to introduce the knowledge of quantitative pharmacology to analyze the association of drug exposure in body with efficacy and adverse reactions,and exploratory indicators should be incorporated for comprehensive analysis.This review provides related experience and new ideas for the clinical research and development of new anti-HBV drugs.

关 键 词：乙型肝炎 慢性 临床试验 药物疗法 

分 类 号：R512.62[医药卫生—内科学]