非肝硬化HBeAg阴性患者停用富马酸替诺福韦酯后的长期反应

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Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients – FINITE study

ThomasBerg1Karl-GeorgSimon2StefanMauss3EckartSchott4RenateHeyne5Dietmar M.Klass6ChristophEisenbach7Tania MaraWelzel8ReinhartZachoval9GiselaFelten10JulianSchulze-zur-Wiesch11MarkusCornberg12Marjoleine L.Op den Brouw13BelindaJump14HansReiser14LotharGallo15TobiasWarger15JörgPetersen16FINITE CHB study investigators [First investigation in stopping TDF treatment after long-term virological suppression in HBeAg-negative chronic hepatitis B]
KeywordsTenofovir disoproxil fumarate  HBeAg-negative  Finite therapy  HBsAg loss

Highlights
• The potential to discontinue tenofovir disoproxil fumarate (TDF) therapy in HBeAg-negative patients was investigated.
• Of the patients who stopped TDF therapy, 62% remained off-therapy to Week 144.
• Four patients (19%) achieved HBsAg loss and three of them achieved HBsAg seroconversion.
• Discontinuing TDF therapy was well-tolerated.
• There is potential for HBsAg loss and/or sustained virological response in non-cirrhotic HBeAg-negative patients stopping long-term TDF therapy.

Background & Aims

There is currently no virological cure for chronic hepatitis B but successful nucleos(t)ide analogue (NA) therapy can suppress hepatitis B virus (HBV) DNA replication and, in some cases, result in HBsAg loss. Stopping NA therapy often leads to viral relapse and therefore life-long therapy is usually required. This study investigated the potential to discontinue tenofovir disoproxil fumarate (TDF) therapy in HBeAg-negative patients.

Methods

Non-cirrhotic HBeAg-negative patients who had received TDF for ≥4 years, with suppressed HBV DNA for ≥3.5 years, were randomly assigned to either stop (n = 21) or continue (n = 21) TDF monotherapy. Standard laboratory tests including HBV DNA viral load, HBsAg and alanine aminotransferase (ALT) measurements, and adverse event reporting were carried out during treatment and post-treatment follow-up for 144 weeks.
Results

Of the patients who stopped TDF therapy, 62% (n = 13) remained off-therapy to Week 144. Median HBsAg change in this group was −0.59 log10 IU/ml (range −4.49 to 0.02 log10 IU/ml) vs. 0.21 log10 IU/ml in patients who continued TDF therapy. Four patients (19%) achieved HBsAg loss. Patients stopping therapy had initial fluctuations in viral load and ALT; however, at Week 144, 43% (n = 9) had either achieved HBsAg loss or had HBV DNA <2,000 IU/ml. There were no unexpected safety issues identified with stopping TDF therapy.
Conclusions

This controlled study demonstrated the potential for HBsAg loss and/or sustained virological response in non-cirrhotic HBeAg-negative patients stopping long-term TDF therapy.

Lay summary: Nucleos(t)ide analogue (NA) is usually a life-long therapy for HBV patients. This randomised controlled study investigated the discontinuation of tenofovir disoproxil fumarate (TDF) therapy in HBeAg-negative patients. Of the patients who stopped TDF therapy, 62% remained off-therapy to Week 144, of which 43% of patients had achieved either HBsAg loss or HBV DNA <2,000 IU/ml. This offers a potential for long-term HBV-suppressed patients without cirrhosis to stop NA therapy under strict surveillance.

Clinical trial number: NCT01320943.

Hepbest

非肝硬化HBeAg阴性患者停用富马酸替诺福韦酯后的长期反应 - 有限研究

关键词替诺福韦酯富马酸盐   HBeAg阴性   有效治疗  HBsAg消失


强调
• 研究了在HBeAg阴性患者中停用替诺福韦二吡呋酯富马酸（TDF）治疗的可能性。
• 在停止TDF治疗的患者中，62％的患者在第144周时停止治疗。
• 4例（19％）达到HBsAg消失，其中3例达到HBsAg血清学转换。
• 停止TDF治疗耐受性良好。
• 在非肝硬化HBeAg阴性患者停止长期TDF治疗时，存在HBsAg消失和/或持续病毒学应答的可能性。


背景和目的
目前对慢性乙型肝炎没有病毒学治愈，但成功的核苷（酸）类似物（NA）治疗可以抑制乙型肝炎病毒（HBV）DNA复制，并且在某些情况下会导致HBsAg消失。停止NA治疗往往导致病毒复发，因此通常需要终身治疗。本研究调查了在HBeAg阴性患者中停用替诺福韦酯富马酸（TDF）治疗的可能性。

方法
非肝硬化HBeAg阴性患者接受TDF≥4年，抑制HBVDNA≥3。5年，随机分为停药（21例）或继续（21例）TDF单药治疗。在治疗和治疗后随访144周期间，进行包括HBV DNA病毒载量，HBsAg和丙氨酸氨基转移酶（ALT）测量以及不良事件报告的标准实验室检测。

结果
在停止TDF治疗的患者中，62％（n = 13）至第144周仍未治疗。该组HBsAg中位数变化为-0.59 log10 IU / ml（范围为-4.49至0.02 log10 IU / ml），而继续TDF治疗组为0.21 log10 IU / ml。 4名患者（19％）达到HBsAg消失。停止治疗的病人有病毒载量和ALT的起始波动;然而，在第144周，43％（n = 9）已经达到HBsAg消失或HBV DNA <2,000 IU / ml。没有意外的安全问题确定停止TDF治疗。


结论
这项对照研究显示，非肝硬化HBeAg阴性患者停止长期TDF治疗可能导致HBsAg消失和/或持续病毒学应答。

总结：核苷（酸）类似物（NA）通常是HBV患者的终身治疗。这项随机对照研究调查了HBeAg阴性患者停用富马酸替诺福韦酯（TDF）治疗。在停止TDF治疗的患者中，62％的患者至第144周仍处于停药治疗，其中43％的患者达到HBsAg消失或HBV DNA <2,000 IU / ml。这为未经肝硬化的长期HBV抑制患者提供了在严格监测下停止NA治疗的潜力。

临床试验号码：NCT01320943。

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文章链接：
https://www.sciencedirect.com/science/article/pii/S0168827817321554

说明，核苷酸停药后，部分免疫力激活，导致表抗清除；
停药时表抗介于2.5-5.5 Log10IU/ml， 而停药后表抗下降的，都是表抗滴度较低的