AASLD2020[819] NAP前後的HBsAg同工型分析 REP 301，REP 301-LTF中的聯

StephenW

819
ANALYSIS OF HBsAg ISOFORMS DURING AND AFTER NAPBASED
COMBINATION THERAPY IN THE REP 301, REP 301-LTF
AND REP 401 STUDIES
Michel Bazinet1, Mark Anderson2, Victor Pântea3, Gheorghe
Placinta4, Iurie Moscalu5, Valentin Cebotarescu3, Lilia
Cojuhari3, Pavlina Jimbei6, Liviu Iarovoi4, Valentina Smesnoi6,
Tatiana Musteata6, Alina Jucov7, Jeffrey Gersch2, Vera
Holzmayer2, Mary Kuhns2, Gavin Cloherty2 and Andrew
Vaillant1, (1)Replicor Inc., (2)Abbott Diagnostics, Abbott
Park, IL, USA, (3)Department of Infectious Diseases, Nicolae
Testemiţanu State University of Medicine and Pharmacy, (4)
Department of Infectious Diseases, Nicolae Testemitanu
State University of Medicine and Pharmacy, (5)Spitalul Clinic
Republican, Moldova, (6)Toma Ciorbă Infectious Clinical
Hospital, (7)Nicolae Testemitanu State University of Medicine
and Pharmacy of the Republic of Moldova
Background: In HBeAg negative HBV mono-infection, NAP
combination therapy achieved 78% virologic control (HBV DNA
≤ 2000 IU/mL, normal ALT [VC]) with 39% further achieving
functional cure (HBsAg < 0 05 IU/mL, HBV DNA target not
detected, normal ALT [FC]) (REP 401 study, NCT02565719)
Retrospective inclusion of participants with HBeAg negative
HBV / HDV co-infection receiving suboptimal NAP-based
combination therapy (REP 301 study, NCT02233075 and
REP 301-LTF study, NCT02876419) yielded combined HBV
outcomes of 18/52 (35%) FC, 19/52 (36%) VC and 15/52
(29%) rebound (R) The goal of this study was to analyze
the dynamics of S-HBsAg, M-HBsAg and L-HBsAg during
and after NAP therapy in the REP 301 / 301-LTF and 401
studies Methods: Frozen serum samples (n=1153) from all
52 participants in the REP 301 / REP 301-LTF and REP 401
studies were analyzed using the Abbott research use only
(RUO) assays for HBsAg isoforms (large [L], medium [M] and
total [T]) T-HBsAg was used to assess total HBsAg present
From this population of HBsAg, the presence of M-HBsAg
and L-HBsAg was determined The relative change over time
in S-HBsAg relative to the other isoforms was inferred by
the change in the ratio over time of T-HBsAg to M-HBsAg
Measurements with S/Co < 1 were excluded from the ratio
/ trend analysis Results: qHBsAg reduction from baseline
> 2 log10 IU/mL was observed in 40/52 participants A more
rapid reduction of S-HBsAg relative to the reduction of other
HBsAg isoforms occurred in 37/40 of these participants,
consistent with the selective targeting of SVP assembly and
secretion by NAPs Selective S-HBsAg loss was not observed
in 11/12 participants with qHBsAg reduction ≤ 2log10 from
baseline, suggesting the more moderate HBsAg responses
were due to suboptimal inhibition of SVP assembly At the
end of follow-up, all HBsAg isoforms were detectable (S/
Co > 1) in 0/18 (FC), 17/19 (VC) and 15/15 (R) participants.
Conclusion: Selective effects on S-HBsAg clearance during
NAP therapy are consistent with selective inhibition of SVP
assembly and secretion on human HBV infection during NAP
therapy Suppression of all HBsAg isoforms during follow-up
in participants establishing functional cure indicate the control established is profound.

StephenW

819
NAP前後的HBsAg同工型分析
REP 301，REP 301-LTF中的聯合治療
AND REP 401研究
Michel Bazinet1，Mark Anderson2，VictorPântea3，Gheorghe
Placinta4，Iurie Moscalu5，Valentin Cebotarescu3，Lilia
Cojuhari3，Pavlina Jimbei6，Liviu Iarovoi4，Valentina Smesnoi6，
Tatiana Musteata6，Alina Jucov7，Jeffrey Gersch2，Vera
Holzmayer2，Mary Kuhns2，Gavin Cloherty2和Andrew
Vaillant1，（1）Replicor Inc。，（2）Abbott Diagnostics，Abbott
美國伊利諾伊州帕克市（3）尼古拉（Nicolae）傳染病科
德斯塔米納努國立醫科大學（4）
Nicolae Testemitanu傳染病科
國立醫藥大學，（5）Spitalul診所
共和黨人，摩爾多瓦，（6）托馬·西奧巴傳染性臨床
醫院，（7）尼古拉·德斯塔米塔努國立醫科大學
和摩爾多瓦共和國藥房
背景：在HBeAg陰性HBV單一感染中，NAP
聯合療法實現了78％的病毒學控制（HBV DNA
≤2000 IU / mL，正常ALT [VC]），進一步達到39％
功能性治愈（HBsAg <0 05 IU / mL，HBV DNA靶標未達到
檢測到，正常ALT [FC]）（REP 401研究，NCT02565719）
回顧性納入HBeAg陰性的參與者
HBV / HDV合併感染獲得基於NAP的次優
聯合療法（REP 301研究，NCT02233075和
REP 301-LTF研究（NCT02876419）獲得了合併的HBV
18/52（35％）FC，19/52（36％）VC和15/52的結局
（29％）反彈（R）這項研究的目的是分析
S-HBsAg，M-HBsAg和L-HBsAg的動態
在REP 301 / 301-LTF和401中進行NAP治療後
研究方法：從所有冷凍血清樣本（n = 1153）
REP 301 / REP 301-LTF和REP 401的52名參與者
僅使用雅培研究分析了研究
（RUO）測定HBsAg亞型（大[L]，中[M]和
總[T]）T-HBsAg用於評估總的HBsAg
從這批HBsAg中，存在M-HBsAg
確定L-HBsAg隨時間的相對變化
S-HBsAg中相對於其他同工型的
T-HBsAg與M-HBsAg的比率隨時間的變化
S / Co <1的測量被排除在比率之外
/趨勢分析結果：qHBsAg從基線降低
在40/52名參與者中觀察到> 2 log10 IU / mL
S-HBsAg相對於其他抗體的減少迅速減少
這些參與者中有37/40發生了HBsAg亞型，
與SVP組裝的選擇性定位一致，並且
NAP的分泌未觀察到選擇性S-HBsAg丟失
來自11/12的qHBsAg降低≤2log10的參與者
基線，提示較溫和的HBsAg反應
是由於對SVP裝配的抑制不理想
隨訪結束時，所有HBsAg亞型均可檢出（S /
Co> 1）在0/18（FC），17/19（VC）和15/15（R）參與者中。
結論：對S-HBsAg清除的選擇性作用
NAP治療與選擇性抑制SVP一致
NAP期間對人HBV感染的聚集和分泌
隨訪過程中所有HBsAg亞型的抑制
在建立功能性治療的參與者中，建立的控制是深遠的。

newchinabok

这个药就算了