慢性乙型肝炎（CHB）长期核苷（酸）类似物（Nuc）治疗可能会抑制乙型肝炎病毒（HBV），使丙氨酸转氨酶（ALT）正常化，改善组织学病变，并预防肝病进展。但很少能实现 HBsAg 消失，这是功能性治愈的标志。 HBeAg 阴性 CHB 患者经常被建议继续 Nuc 治疗，直到 HBsAg 消失，这通常意味着无限期。然而，长期/终生 Nuc 治疗会增加成本，并担心因依从性差和/或自行停止/失访而导致不良后果。因此，2012年亚太指南建议HBeAg阴性CHB患者在HBV DNA检测不到≥12个月后可以停止Nuc治疗。随后的亚洲和少数欧洲研究发现有限 Nuc 治疗策略是可行且相当安全的。 2016-2017年，美国和欧洲指南也将停止Nuc作为HBeAg阴性CHB患者的有条件策略纳入其中。此外，据记录，随着 Off-Nuc 随访时间的延长，HBsAg 消失率逐渐增加，在白种人中更高，在亚洲患者 4-5 岁以后更为明显。最近，一项针对 HBV 肝硬化患者的大型研究显示，不仅 10 年 HBsAg 消失率较高（15.3% vs. 1.6%），而且 10 年肝细胞癌发病率也降低了约 50%（16.5% vs. 29.5%），并且降低了 60%与继续 Nuc 治疗的匹配良好的患者相比，停止 Nuc 后肝脏相关死亡率/移植率（6.1% vs. 15.1%）。由于旨在功能性治愈的新药开发并不令人满意，HBeAg 阴性 CHB 的有限 Nuc 治疗策略似乎是当今功能性治愈的最佳现实选择。版权所有 © 2024 美国肝病研究协会。

Long-term nucleos(t)ide analogue (Nuc) therapy in chronic hepatitis B (CHB) may lead to hepatitis B virus (HBV) suppression, alanine aminotransferase (ALT) normalization, improvement of histological lesions, and prevention of liver disease progression, but rarely achieve HBsAg loss, the hallmark of functional cure. HBeAg-negative CHB patients have often been recommended to continue Nuc therapy until HBsAg loss, which usually means indefinitely. However, long-term/life-long Nuc therapy is associated with increasing costs and concerns of adverse outcomes subsequent to poor adherence and/or self-cessation/loss-to-follow-up. Hence, 2012 Asian-Pacific guidelines recommended that HBeAg-negative CHB patients can stop Nuc therapy after ≥12 months of HBV DNA undetectability. Subsequent Asian and few European studies have found the strategy of finite Nuc therapy to be feasible and reasonably safe. In 2016-2017, stopping Nuc was also included as a conditional strategy for HBeAg-negative CHB patients in the American and European guidelines. Furthermore, progressively increasing HBsAg loss rates with prolongation of off-Nuc follow-up were documented, being higher in Caucasians and more apparent beyond years 4-5 in Asian patients. Recently, a large study in patients with HBV cirrhosis showed not only higher 10-year HBsAg loss rate (15.3 vs. 1.6%) but also ~50% lower 10-year hepatocellular carcinoma incidence (16.5 vs. 29.5%) and 60% lower liver-related mortality/transplantation rate (6.1 vs. 15.1%) after Nuc cessation, as compared with well-matched patients continuing Nuc therapy. Since novel drug development aiming for functional cure has not been satisfactory, the strategy of finite Nuc therapy in HBeAg-negative CHB seems to be the best realistic option for functional cure today.Copyright © 2024 American Association for the Study of Liver Diseases.