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在 HBeAg 血清学转换后停止使用核苷(酸)类似物治疗的高加索乙型肝炎患者,复发率高,结局致命。

Stopping nucleos(t)ide analogue treatment in Caucasian hepatitis B patients after HBeAg seroconversion is associated with high relapse rates and fatal outcomes.

机构信息

Antwerp, Belgium.

Rotterdam, The Netherlands.

出版信息

Aliment Pharmacol Ther. 2018 Apr;47(8):1170-1180. doi: 10.1111/apt.14560. Epub 2018 Mar 2.

Abstract

BACKGROUND

Stopping nucleos(t)ide analogues (NA) after hepatitis B e antigen (HBeAg) seroconversion is associated with high relapse rates in Asian patients, but data in Caucasian cohorts are scarce. Clinical course, outcomes and immunological aspects of chronic hepatitis B infections differ substantially between distinct ethnicities.

AIM

The aim of this study was to determine relapse rates, factors predicting relapse and clinical outcomes after nucleos(t)ide analogue cessation in a large, predominantly Caucasian cohort of chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion.

METHODS

This is a nationwide observational cohort study including HBeAg positive, mono-infected chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion from 18 centres in Belgium.

RESULTS

A total of 98 patients with nucleo(s)tide analogue-induced HBeAg seroconversion were included in the study. Of the 62 patients who stopped treatment after a median consolidation treatment of 8 months, 30 relapsed. Higher gamma-glutamyl transferase levels at both treatment initiation (HR 1.004; P = 0.001 per unit increment) and HBeAg seroconversion (HR 1.006; P = 0.013 per unit increment) were associated with an increased risk of clinically significant relapse in a multivariate Cox regression model. Treatment cessation led to liver-related death in 2 patients, of whom one showed a severe flare. Of the patients who continued treatment after HBeAg seroconversion, none relapsed or developed severe hepatic outcomes.

CONCLUSION

Treatment withdrawal in Caucasian chronic hepatitis B patients after nucleos(t)ide analogue-induced HBeAg seroconversion results in viral relapses in more than half of patients with potential fatal outcomes. These real-world data further lend support to preferentially continue NA treatment after HBeAg seroconversion until HBsAg loss.

摘要

背景

乙型肝炎 e 抗原(HBeAg)血清学转换后停止核苷(酸)类似物(NA)治疗与亚洲患者的高复发率相关,但在白种人群队列中的数据很少。慢性乙型肝炎感染的临床过程、结局和免疫学特征在不同种族之间有很大差异。

目的

本研究旨在确定核苷(酸)类似物诱导的 HBeAg 血清学转换后,在一个以白种人为主的、具有代表性的慢性乙型肝炎患者大队列中,停止核苷(酸)类似物治疗后的复发率、预测复发的因素和临床结局。

方法

这是一项全国性观察性队列研究,纳入了来自比利时 18 个中心的 HBeAg 阳性、单感染的慢性乙型肝炎患者,这些患者接受核苷(酸)类似物治疗后发生了 HBeAg 血清学转换。

结果

共有 98 例核苷(酸)类似物诱导的 HBeAg 血清学转换患者纳入本研究。在中位巩固治疗 8 个月后,62 例患者停止治疗,其中 30 例复发。在多变量 Cox 回归模型中,治疗开始时(HR 1.004;每单位增量 P=0.001)和 HBeAg 血清学转换时(HR 1.006;每单位增量 P=0.013)较高的γ-谷氨酰转移酶水平与临床显著复发的风险增加相关。在 2 例患者中,治疗停止导致与肝脏相关的死亡,其中 1 例出现严重的肝炎发作。在 HBeAg 血清学转换后继续治疗的患者中,无患者复发或出现严重的肝脏结局。

结论

在白种人慢性乙型肝炎患者中,核苷(酸)类似物诱导的 HBeAg 血清学转换后停止治疗,超过一半的患者会出现病毒复发,并有潜在的致命结局。这些真实世界的数据进一步支持在 HBeAg 血清学转换后优先继续使用 NA 治疗,直至 HBsAg 丢失。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83c5/5900846/2360f04f3301/APT-47-1170-g001.jpg

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