在基於NAP的聯合治療期間，轉氨酶升高對建立功能性治愈HBV

StephenW

Benefit of transaminase elevations in establishing functional cure of HBV infection during NAP‐based combination therapy
Michel Bazinet
Victor Pântea
Gheorghe Placinta
Iurie Moscalu
Valentin Cebotarescu
Lilia Cojuhari
Pavlina Jimbei
Liviu Iarovoi
Valentina Smesnoi
Tatiana Musteata
Alina Jucov
… See all authors
First published: 08 February 2021
https://doi.org/10.1111/jvh.13483

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1111/jvh.13483
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Abstract

Treatment of HBV infection with nucleic acid polymers and pegIFN is accompanied by transaminase elevations in 95% of participants. HBV viral rebound, partial cure (HBV DNA < 2000 IU/mL, normal ALT) or functional cure (HBV DNA target not detected, HBsAg < LLOQ, normal ALT) occurred in 27%, 38% and 35% of participants. Correlations between ALT, AST and GGT elevations, virologic baseline, response during therapy and HBV therapeutic outcome were investigated.

A retrospective analysis of all 40 participants in the REP 401 study (NCT02565719) included maxima and area under the curve for ALT, AST and GGT, baseline virology, HBsAg and anti‐HBs response and HBV therapeutic outcomes.

ALT, AST and GGT elevations were asymptomatic, independent of baseline virologic status and anti‐HBs response but correlated with HBsAg reduction ≥ 3 log10 from baseline. Functional cure was associated with significantly lower HBsAg during the nadir of ALT flares versus viral rebound or partial cure. ALT elevations > 3X ULN while HBsAg was < 1 IU/mL occurred in 3/11 (27%), 11/15 (74%) and 14/14 (100%) of participants experiencing viral rebound, partial or functional cure. ALT elevation > 3X ULN during HBsAg < 1 IU/mL and < 10 IU/mL were the best predictors of partial and functional cure.

In conclusion, elevations in ALT, AST or GGT while HBsAg < 10 IU/ml during therapy with REP 2139 + pegIFN are associated with partial and functional cure. More potent HBsAg reduction during flare nadir is associated with the establishment of functional cure, suggesting a critical role for HBsAg‐specific immunity to achieve this outcome. These on‐therapy milestones may have similar positive prognostic value with other combination therapies.

StephenW

在基于NAP的联合治疗期间，转氨酶升高对建立功能性治愈HBV感染的益处
米歇尔·巴赞特
维克多·潘特（VictorPântea）
格奥尔格·普拉辛塔
尤里·莫斯卡鲁（Iurie Moscalu）
瓦伦丁·塞伯塔雷斯库（Valentin Cebotarescu）
莉莉亚·科朱哈里（Lilia Cojuhari）
帕夫利娜·金贝（Pavlina Jimbei）
利维·阿罗沃维（Liviu Iarovoi）
瓦伦蒂娜（Valentina Smesnoi）
塔蒂亚娜·穆斯塔塔（Tatiana Musteata）
阿丽娜·朱科夫（Alina Jucov）
…查看所有作者
首次发布：2021年2月8日
https://doi.org/10.1111/jvh.13483

本文已被接受发表并接受了完整的同行评审，但尚未经过文案编辑，排版，分页和校对过程，这可能会导致此版本与Record版本之间的差异。请引用本文作为doi：10.1111 / jvh.13483
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用核酸聚合物和pegIFN治疗HBV感染伴随着95％的参与者的转氨酶升高。分别有27％，38％和35％的参与者发生了HBV病毒反弹，部分治愈（HBV DNA <2000 IU / mL，正常ALT）或功能性治愈（未检测到HBV DNA目标，HBsAg <LLOQ，正常ALT）。研究了ALT，AST和GGT升高，病毒学基线，治疗期间反应和HBV治疗结果之间的相关性。

对REP 401研究（NCT02565719）中所有40名参与者的回顾性分析包括ALT，AST和GGT曲线下的最大值和面积，基线病毒学，HBsAg和抗HBs反应以及HBV治疗结果。

ALT，AST和GGT升高无症状，与基线病毒学状况和抗HBs反应无关，但与HBsAg从基线降低≥3 log10相关。与病毒反弹或部分治愈相比，功能性治愈与ALT爆发最低时的HBsAg明显降低有关。当病毒反弹，部分或功能性治愈的参与者中，有3/11（27％），11/15（74％）和14/14（100％）的ALT升高> 3X ULN，而HBsAg <1 IU / mL。 HBsAg <1 IU / mL和<10 IU / mL期间ALT升高> 3倍ULN是部分治愈和功能治愈的最佳预测指标。

总之，在用REP 2139 + pegIFN治疗期间，HBsAg <10 IU / ml时，ALT，AST或GGT升高与部分和功能治愈有关。在爆发最低点期间更有效地降低HBsAg与功能性治愈的建立有关，这表明HBsAg特异性免疫对于实现这一结果至关重要。这些治疗上的里程碑可能与其他联合疗法具有相似的积极预后价值。

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