在治疗至少8年后停用替诺福韦地索普西富马酸盐治疗慢性乙

StephenW

Lancet Gastroenterol Hepatol. 2019 Feb 19. pii: S2468-1253(19)30015-9. doi: 10.1016/S2468-1253(19)30015-9. [Epub ahead of print]
Safety and efficacy of stopping tenofovir disoproxil fumarate in patients with chronic hepatitis B following at least 8 years of therapy: a prespecified follow-up analysis of two randomised trials.
Buti M1, Wong DK2, Gane E3, Flisiak R4, Manns M5, Kaita K6, Janssen HLA2, Op den Brouw M7, Jump B8, Kitrinos K8, Crans G8, Flaherty J8, Gaggar A8, Marcellin P9.
Author information
Abstract
BACKGROUND:

Effective and well tolerated nucleos(t)ide analogue treatment exists for patients with chronic hepatitis B, although treatment is generally anticipated to be life-long, with concomitant costs and treatment-related side-effects. We aimed to characterise the outcomes of patients with persistent viral suppression who discontinued nucleotide analogue use after extended treatment.
METHODS:

The primary objective of this prespecified analysis was to evaluate the safety of stopping long-term tenofovir disoproxil fumarate therapy in patients enrolled in two (completed) randomised controlled studies, GS-US-174-0102 (ClinicalTrials.gov, number NCT00117676) and GS-US-174-0103 (ClinicalTrials.gov, number NCT00116805). In those studies, patients who had completed 8 years or more of nucleotide analogue treatment, were hepatitis B surface antigen (HBsAg)-positive with hepatitis B virus (HBV) DNA concentration of less than 29 IU/mL, and were unwilling or unable to continue therapy were required by protocol to enter a 24-week treatment-free follow-up (TFFU) phase. We present data for patients in the TFFU phase who were assessed at baseline and monitored every 4 weeks for changes in qualitative serum HBsAg, HBV DNA, and alanine aminotransferase (ALT) concentrations in addition to standard safety assessments.
FINDINGS:

Of 124 patients who entered the TFFU phase, 54 (44%) patients did not complete 24 weeks of follow-up (median 12 weeks; IQR 0-20). Overall, 32 (26%) patients reported an adverse event. Serious adverse events occurred in five (4%) patients, including elevated ALT concentrations in two patients, hepatic flare in two patients, and increased lipase in one patient. 38 (31%) of patients had grade 3 or higher laboratory abnormalities, the majority of which were ALT elevations (36 patients). Of the 106 hepatitis B e antigen (HBeAg)-negative patients who entered the TFFU phase, 63 (59%) were followed for 24 weeks. HBsAg loss was observed in five (5%) of the 106 HBeAg-negative patients who entered the TFFU phase, and 37 (35%) had both HBV DNA concentrations of less than 2000 IU/mL and ALT concentrations less than the ULN at TFFU week 24. 18 HBeAg-positive patients entered the TFFU phase, of whom seven (39%) were followed up for 24 weeks. Of these seven patients, none had HBsAg loss or HBV DNA of less than 2000 IU/mL and one (14%) had an ALT less than the ULN at week 24.
INTERPRETATION:

Within 24 weeks of stopping 8 years or more of nucleotide analogue therapy almost a third of patients experienced a grade 3 or higher laboratory abnormality. Although few patients achieved HBsAg loss, a subgroup of HBeAg-negative patients can achieve a low-replicative state within a short duration of follow-up.
FUNDING:

Gilead Sciences, Inc.

Copyright © 2019 Elsevier Ltd. All rights reserved.

PMID:
    30795958
DOI:
    10.1016/S2468-1253(19)30015-9

StephenW

柳叶刀Gastroenterol Hepatol。 2019年2月19日.pii：S2468-1253（19）30015-9。 doi：10.1016 / S2468-1253（19）30015-9。 [印刷前的电子版]
在治疗至少8年后停用替诺福韦地索普西富马酸盐治疗慢性乙型肝炎的安全性和有效性：两项随机试验的预先指定的随访分析。
Buti M1，Wong DK2，Gane E3，Flisiak R4，Manns M5，Kaita K6，Janssen HLA2，Op den Brouw M7，Jump B8，Kitrinos K8，Crans G8，Flaherty J8，Gaggar A8，Marcellin P9。
作者信息
抽象
背景：

对于患有慢性乙型肝炎的患者存在有效且耐受良好的核苷（t）ide类似物治疗，尽管通常预期治疗是终生的，伴随着成本和与治疗相关的副作用。我们的目的是描述持续性病毒抑制患者的结果，这些患者在延长治疗后停止使用核苷酸类似物。
方法：

该预先指定的分析的主要目的是评估在两项（完成的）随机对照研究（GS-US-174-0102（ClinicalTrials.gov，编号NCT00117676）和GS）中纳入长期替诺福韦地索普西富马酸盐治疗的安全性。 -US-174-0103（ClinicalTrials.gov，编号NCT00116805）。在那些研究中，完成了8年或更长时间的核苷酸类似物治疗的患者，乙型肝炎病毒表面抗原（HBsAg）阳性，乙型肝炎病毒（HBV）DNA浓度低于29 IU / mL，并且不愿或无法方案要求继续治疗进入24周无治疗随访（TFFU）阶段。我们提供了TFFU期患者的数据，这些患者在基线时进行了评估，并且每4周监测一次定性血清HBsAg，HBV DNA和丙氨酸氨基转移酶（ALT）浓度的变化以及标准安全性评估。
发现：

在进入TFFU期的124名患者中，54名（44％）患者未完成24周的随访（中位数12周; IQR 0-20）。总体而言，32名（26％）患者报告了不良事件。 5例（4％）患者出现严重不良事件，其中2例患者ALT浓度升高，2例患者肝脏发作，1例患者脂肪酶升高。 38例（31％）患者出现3级或更高级别的实验室异常，其中大部分为ALT升高（36例）。在进入TFFU期的106名乙型肝炎e抗原（HBeAg）阴性患者中，63名（59％）随访24周。进入TFFU期的106名HBeAg阴性患者中有5名（5％）观察到HBsAg丢失，37名（35％）HBV DNA浓度低于2000 IU / mL且ALT浓度低于TFFU的ULN第24周.18例HBeAg阳性患者进入TFFU期，其中7例（39％）随访24周。在这7名患者中，没有人HBsAg丢失或HBV DNA低于2000 IU / mL，一名（14％）患者的ALT低于第24周的ULN。
解释：

在停止使用8年或更长时间的核苷酸类似物治疗的24周内，几乎三分之一的患者经历了3级或更高级别的实验室异常。虽然很少有患者达到HBsAg丢失，但HBeAg阴性患者亚组可在短期随访期间达到低复制状态。
资金：

吉利德科学公司

版权所有©2019 Elsevier Ltd.保留所有权利。

结论：
    30795958
DOI：
    10.1016 / S2468-1253（19）30015-9