EASL2020[LBP33]HBsAg水平，HBsAg亚型，HBsAg免疫分析 复合物，HBV前

StephenW

LBP33
Analysis of HBsAg levels, HBsAg isoforms, HBsAg immune
complexes, HBV pregenomic RNA and HBcrAg dynamics during
and after NAP-based combination therapy in the REP 301-LTF and
REP 401 studies
Michel Bazinet1, Mark Anderson2, Victor Pantea3, Gheorghe Placinta3,
Iurie Moscalu4, Valentin Cebotarescu3, Lilia Cojuhari3,
Pavlina Jimbei5, Liviu Iarovoi3, Valentina Smesnoi5, Tatiana Musteata5,
Alina Jucov3,4, Jeff Gersch2, Vera Holzmayer2, Mary Kuhns2,
Gavin Cloherty2, Andrew Vaillant1. 1Replicor Inc., Montreal, Canada;
2Abbott Diagnostics, Illinois, United States; 3Nicolae Testemiţanu State
University of Medicine and Pharmacy, Department of Infectious
Diseases, Chișinău, Moldova; 4ARENSIA Exploratory Medicine,
Republican Clinical Hospital, Chișinău, Moldova; 5Toma Ciorbǎ
Infectious Clinical Hospital, Chișinău, Moldova
Email: [email protected].
Background and aims: After completion of NAP-based combination
therapy with pegIFN and follow-up in the REP 301-LTF study (3.5
years) and REP 401 study (48 weeks), combined HBV outcomes were
functional cure (HBsAg <0.05 IU/mL, HBV DNA target not detected,
normal ALT [FC]) in 18/52 (35%), virologic control (HBV DNA
≤2000 IU/mL, normal ALT [VC]) in 19/52 (36%) and rebound (R) in
15/52 (29%) of participants. The goal of this study was to analyze the
relationship between HBV outcome and experimental virologic
markers of HBV infection.
Methods: Frozen serum samples (n = 1153) from all 52 participants in
the REP 301/REP 301-LTF and REP 401 studies were analyzed by the
following:
1. Abbott ARCHITECT HBsAg NEXT (analytical sensitivity 0.005 IU/
mL).
2. Abbott research use only (RUO) assays for HBsAg isoforms (large,
medium, small).
3. Abbott RUO assay for HBsAg/anti-HBs immune complexes
(HBsAg IC).
4. Abbott RUO assay for pregenomic HBV RNA (pgRNA).
5. Fujirebio HBcrAg (LLOQ 3log10 U/mL).
Results: All participants experiencing HBsAg loss (<0.05 IU/mL)
during therapy (28/52) rapidly became negative with HBsAg Next.
HBsAg <0.005 IU/mL was confirmed at the end of follow-up in 18/18
functional cure and 1/1 virologic control participants with previous
HBsAg <0.05 IU/mL.
A more rapid reduction of S-HBsAg relative to the reduction of other
HBsAg isoforms occurred in 39/40 participants with HBsAg decline
>2 log10 from baseline, consistent with targeting SVPs. At the end of
follow-up, HBsAg isoforms were detectable in 0/18 (FC), 17/19 (VC)
and 15/15 (R) participants. HBsAg IC (relative luminescence units or
RLU) were in the positive range in 30/52 participants at baseline and
at the end of follow-up in 0/18 (FC), 5/19 (VC) and 10/15 (R)
participants.
At baseline, HBV RNA and HBcrAg were present in 42 and 34
participants. HBV RNA loss on therapy occurred in 5/ 14 (FC), 5/16
(VC) and 1/12 (R) participants. HBcrAg < LLOQ on therapy occurred in
5/9 (FC), 7/15 (VC) and 3/10 (R) participants. At the end of follow-up,
both HBV RNA and HBcrAg were > LLOQ in 1/18 (FC), 15/19 (VC) and
13/15 (R) participants.
Conclusion: Functional cure of HBV infection following NAP-based
combination therapy is profound, with HBsAg <0.005 IU/mL and both
HBV RNA and HBcrAg < LLOQ. NEXT negativity and the absence of
HBsAg IC RLUs in the positive range at the end of follow-up in FC
participants suggests efficient reduction in integrated HBV DNA.

StephenW

LBP33
HBsAg水平，HBsAg亚型，HBsAg免疫分析
复合物，HBV前基因组RNA和HBcrAg动态
REP 301-LTF中基于NAP的联合治疗后
REP 401研究
Michel Bazinet1，Mark Anderson2，Victor Pantea3，Gheorghe Placinta3，
Iurie Moscalu4，Valentin Cebotarescu3，Lilia Cojuhari3，
Pavlina Jimbei5，Liviu Iarovoi3，Valentina Smesnoi5，Tatiana Musteata5，
Alina Jucov3,4，Jeff Gersch2，Vera Holzmayer2，Mary Kuhns2，
Gavin Cloherty2，Andrew Vaillant1。 1Replicor Inc.，加拿大蒙特利尔；
2美国伊利诺伊州的Abbott Diagnostics； 3尼古拉·Testemiţanu州
医药大学感染系
疾病，基希纳纳，摩尔多瓦； 4ARENSIA探索医学，
摩尔多瓦基希纳纳乌共和医院5托马·西奥巴
摩尔多瓦基希纳纳乌传染临床医院
电子邮件：[email protected]。
背景和目标：完成基于NAP的合并后
REP 301-LTF研究中pegIFN的治疗和随访（3.5
年）和REP 401研究（48周），合并的HBV结果为
功能性治愈（HBsAg <0.05 IU / mL，未检测到HBV DNA目标，
18/52（35％）的正常ALT [FC]），病毒学控制（HBV DNA）
≤2000IU / mL，正常ALT [VC]）在19/52（36％），反弹（R）在19/52
15/52（29％）的参与者。这项研究的目的是分析
HBV结局与实验病毒学之间的关系
HBV感染的标志物。
方法：来自所有52名参与者的冷冻血清样本（n = 1153）
REP 301 / REP 301-LTF和REP 401研究通过
以下：
1.雅培ARCHITECT HBsAg NEXT（分析灵敏度0.005 IU /
毫升）。
2.雅培研究仅用于HBsAg亚型的（RUO）分析（
中，小）。
3.雅培RUO检测HBsAg /抗HBs免疫复合物
（HBsAg IC）。
4.用于基因组前HBV RNA（pgRNA）的雅培RUO分析。
5. Fujirebio HBcrAg（LLOQ 3log10 U / mL）。
结果：所有参与者均出现HBsAg丢失（<0.05 IU / mL）
在治疗期间（28/52），HBsAg Next迅速变为阴性。
随访结束时在18/18中确认HBsAg <0.005 IU / mL
功能治愈和1/1病毒学控制参与者与先前
HBsAg <0.05 IU / mL。
相对于其他S-HBsAg的减少，S-HBsAg的减少更快
HBsAg下降的39/40名参与者中出现HBsAg亚型
与基线相比，> 2 log10，与定位SVP一致。在......的最后
随访中，可在0/18（FC），17/19（VC）中检测到HBsAg亚型
和15/15（R）参与者。 HBsAg IC（相对发光单位或
基线时，有30/52名参与者的RLU）处于阳性范围，
在随访结束时以0/18（FC），5/19（VC）和10/15（R）
参与者。
基线时，HBV RNA和HBcrAg分别存在于42和34中
参与者。治疗中HBV RNA丢失发生在5/14（FC），5/16
（VC）和1/12（R）参与者。 HBcrAg <LLOQ治疗发生于
5/9（FC），7/15（VC）和3/10（R）参与者。在跟进结束时，
HBV RNA和HBcrAg的LLOQ在1/18（FC），15/19（VC）和
13/15（R）参与者。
结论：基于NAP的功能性治愈HBV感染
联合治疗意义深远，HBsAg <0.005 IU / mL，且两者
HBV RNA和HBcrAg <LLOQ。 NEXT消极和缺乏
随访FC结束时HBsAg IC RLU处于阳性范围
参与者建议有效减少整合的HBV DNA。