Nucleoside/Nucleotide analogues (NAs) are widely used for the antiviral treatment of chronic hepatitis B (CHB), however, it is difficult to achieve serum hepatitis B surface antigen (HBsAg) loss with NAs therapy. In recent years, several prospective trails have reported that HBsAg loss (functional cure or clinical cure) also occurs in a small number of hepatitis B e antigen (HBeAg) negative CHB patients who discontinued long-term treatment with NAs. Accordingly, the "stop-to-cure" strategy is proposed. Although the mechanism has not been fully elucidated, the known factors related to serum HBsAg loss with NAs withdrawal include HBV genotype, duration of NAs treatment, serum HBsAg and HBV RNA levels at end-of-treatment, and ethnic differences. In the review, we discuss the best time to stop NAs therapy, the potential markers for predicting relapse after cessation of NAs and the possible mechanism of "stop-to-cure" in HBeAg-negative CHB patients, and propose some suggestions on the time of retreatment.
核苷（酸）类似物（NAs）是最常用的慢性乙型肝炎（CHB）抗病毒治疗药物，但其很难使患者HBsAg消失。近年的一些研究发现，小部分HBeAg阴性CHB患者在NAs停药后可继发血清HBsAg阴转（即功能性治愈或临床治愈），并据此提出“停药-治愈”（stop-to-cure）策略。尽管机制尚未完全阐明，目前已知的停药后血清HBsAg阴转相关因素包括乙型肝炎病毒（HBV）基因型、NAs疗程长短、停药时的HBsAg和HBV RNA水平及人种差异等。本文特就HBeAg阴性CHB患者的最佳停药时机、预测停药复发的潜在标志物及停药-治愈的可能机制进行讨论，并对再治疗时机等提出建议。.