论文部分内容阅读
长期口服抗病毒治疗可以有效抑制HBV DNA复制从而阻断和延缓进展为肝硬化和肝细胞癌，基于干扰素的治疗可以在部分患者实现持续病毒学应答，在少部分患者甚至可以达到HBsAg消失。目前国内外以慢性乙型肝炎临床治愈（HBsAg消失）为目标新药包括：口服核心蛋白抑制剂，耐受性和安全性良好，能有效降低HBV DNA和HBV RNA,但单用不能有效降低HBsAg水平；注射用干扰RNA或反义RNA，可以有效地降低HBsAg水平，且持续时间较长；免疫调节剂只能带来轻微的HBsAg水平下降，但同时也可能带来免疫相关的不良事件。在不远的将来,通过设计新颖的临床试验，探索不同机制的抗HBV新药联合或序贯应用，有可能实现慢性乙型肝炎的临床治愈。“,”Long term antiviral therapy with nucleos(ti)ide analogues could suppress HBV viral load thereby prevent the progression to cirrhosis and hepatocellular carcinoma. Interferon-based therapy could result in sustained virological response in a fair proportion of patients and even HBsAg loss in a small proportion of them. Novel therapies aiming at functional cure (loss of HBsAg) are under active development. Among the categories of many, HBV core protein inhibitors are safe and could suppress the HBV DNA and HBV RNA, but only with modest effect on the level of HBsAg; silencing of HBV mRNA by siRNA or antisense oligonucleotides could produce meaningful and sustainable declining in HBsAg levels; immune modulators with different mode of action showed modest effect on the reduction of HBsAg, but with noticeable adverse event (especially transaminase flares) related to the mode of action. Novel clinical trial design on the combination or sequential use of innovative molecules will ultimately lead to the functional cure of CHB in the near future.