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慢性乙型肝炎口服抗病毒药物停药:系统评价。

Discontinuation of oral antivirals in chronic hepatitis B: A systematic review.

机构信息

Academic Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital of Athens, Athens, Greece.

4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece.

出版信息

Hepatology. 2016 May;63(5):1481-92. doi: 10.1002/hep.28438. Epub 2016 Mar 4.

Abstract

UNLABELLED

The possibility of safe discontinuation of therapy with nucleos(t)ide analogues (NAs) remains one of the most controversial topics in the management of chronic hepatitis B. Therefore, we systematically reviewed the existing data on NA discontinuation in this setting and tried to identify factors affecting the probability of posttherapy remission. A literature search was performed in order to identify all published studies including patients who discontinued NAs in virological remission (VR) and were followed for ≥12 months thereafter. Twenty-five studies with 1716 patients were included. The pooled rates of durable VR remission were 51.4%, 39.3%, and 38.2% at 12, 24, and 36 months, respectively, after NA discontinuation, being relatively higher in initially hepatitis B e antigen (HBeAg)-positive patients (62.5%, 53.4%, 51.5%) than HBeAg-negative patients (43.7%, 31.3%, 30.1%) (P = 0.064). The weighted probability of durable biochemical remission was 65.4%, being numerically higher in HBeAg-positive than HBeAg-negative patients (76.2% versus 56.7%, P = 0.130). The weighted probability of hepatitis B surface antigen loss was 2.0%. The rates of durable VR did not significantly differ according to the VR definition (hepatitis B virus DNA <200, < 2000, < 20,000 IU/mL) or duration of on-therapy VR in HBeAg-positive patients, but they were significantly higher in studies with HBeAg-negative patients and on-therapy VR > 24 than ≤ 24 months (VR at 12 months off-NAs: 75.0% versus 35.6%, P = 0.005). The weighted probability of durable HBeAg seroconversion was 91.9% and 88.0% at 12 and 24 months, respectively, after NA discontinuation without being affected by the duration of on-therapy VR or consolidation therapy (>6 months in all studies).

CONCLUSION

Durable VR seems to be feasible in a substantial proportion of patients who discontinue long-term NA therapy; on-therapy VR > 24 months offers higher chances of off-NA VR in patients with HBeAg-negative chronic hepatitis B.

摘要

目的

核苷(酸)类似物(NAs)治疗停药的安全性仍然是慢性乙型肝炎管理中最具争议的话题之一。因此,我们系统地回顾了现有关于该背景下 NA 停药的数据,并试图确定影响治疗后缓解概率的因素。为了识别所有发表的研究,进行了文献检索,这些研究包括在病毒学缓解(VR)中停止使用 NAs 并随后随访至少 12 个月的患者。共纳入 25 项研究,1716 例患者。NA 停药后 12、24 和 36 个月时,持久 VR 缓解的累积率分别为 51.4%、39.3%和 38.2%,最初 HBeAg 阳性患者(62.5%、53.4%、51.5%)相对较高,而 HBeAg 阴性患者(43.7%、31.3%、30.1%)较低(P=0.064)。持久生化缓解的加权概率为 65.4%,HBeAg 阳性患者略高于 HBeAg 阴性患者(76.2%对 56.7%,P=0.130)。HBsAg 丢失的加权概率为 2.0%。在 HBeAg 阳性患者中,根据 VR 定义(HBV DNA<200、<2000、<20000 IU/mL)或治疗期 VR 持续时间,持久 VR 率无显著差异,但在 HBeAg 阴性患者和治疗期 VR>24 个月的患者中显著更高(停药后 12 个月的 VR:75.0%对 35.6%,P=0.005)。NA 停药后 12 和 24 个月时,持久 HBeAg 血清学转换的加权概率分别为 91.9%和 88.0%,不受治疗期 VR 或巩固治疗时间(所有研究均>6 个月)的影响。

结论

在相当一部分停止长期 NA 治疗的患者中,持久 VR 似乎是可行的;在 HBeAg 阴性慢性乙型肝炎患者中,治疗期 VR>24 个月可提高停药后 VR 的机会。

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