AASLD2018[530]可检测的Hbcrag或基因组前HBV 核苷类似物时血清中

StephenW

s 530
Does Detectable Hbcrag or Pre-Genomic HBV
RNA in Serum at Time of Nucleoside Analogue
Therapy Withdrawal Predict Severe ALT Flare
Outcome and the Need to Restart Therapy?
Ivana Carey1, Emily K. Butler2, Matthew Bruce1, Jeffrey
Gersch2, Bo Wang1, Mary Kuhns2, Gavin Cloherty2, Geoffrey
M. Dusheiko1 and Kosh Agarwal1, (1)Institute of Liver Studies,
King’s College Hospital, (2)Infectious Disease Research,
Abbott Laboratories
Background: Withdrawal of nucleos(t)ide analogue (NA) in
long-term HBV supressed chronic hepatitis B (CHB) patients
can lead to reductions in HBV DNA and HBsAg loss in some
patients. In contrast, some patients require re-starting NA
therapy. There is an important need to predict the outcome
after treatment withdrawal. Two novel serum markers of
HBV replication/transcriptional activity – hepatitis B corerelated
antigen (HBcrAg) and pregenomic (pg) HBV RNA
might add insight into predicting the variable outcome. Aim:
To assess whether quantitative HBsAg, HBcrAg and pg HBV
RNA levels and their kinetics after NA withdrawal can predict
significant ALT flares (ALT >10xUNL) requiring re-initiation of
NA therapy. Methods: 15 CHB HBeAg negative, non-cirrhotic
patients, (median fibroscan 4.7kPa) suppressed for >3 years
(median 5.1 years, range 3.2-11.8 years) on tenofovir stopped
antiviral therapy and were followed every 4 weeks in the first
6 months and then every 8 weeks thereafter (median duration
52 weeks, range 16-52 weeks). Historical on-treatment
plasma samples (baseline of NUC therapy, year 3, year 5 and
year 7 where available) at treatment withdrawal (EOT) and
at post treatment 4, 8, 12, 16, 24, 32 and 52 weeks were
collected. HBV DNA (TaqMan Roche PCR) [IU/ml], HBsAg
(Abbott Architect) [IU/ml], HBcrAg (CLEIA Fujirebio) [log10U/
ml] and Abbott pg HBV RNA Research Assay [log10U/ml]
were compared between patients with mild ALT flares (ALT>2
x UNL and resolved spontaneously (n=7) vs. patients with
significant ALT flares (ALT> 10 UNL, HBV DNA> 100,000 IU/
ml) (n=3) (all restarted NA) vs. patients with no ALT flares
(n=5) after NA therapy withdrawal. Results: During antiviral
treatment all patients had undetectable HBV DNA after 6
months; the median HBsAg decline was 18 IU/ml per month.
Seven/15 patients had detectable HBcrAg at start of therapy
vs. 1 patient at EOT. HBV RNA (LOQ 1.65 log10 U/ml) was
detected in 12/15 patients at start of therapy vs. 2 patients at
EOT. Serum ALT were normal in all patients at EOT (median
34 IU/l).The median changes in HBV DNA, HBsAg, HBcrAg,
pg HBV RNA and ALT post-stopping therapy are shown in
Figure 1 (presented according type of flare). Only patients
with significant ALT flares had detectable HBcrAg (>2log10 U/
ml) or detected pg HBV RNA at EOT. No HBsAg loss occurred
in this cohort. Conclusion: 67% of patients had an ALT flare
after withdrawal of NA. 20% of patients had a rise in ALT to
>10 x UNL and HBV DNA > 100.000 IU/ml post treatment.
All patients with this degree of ALT flare had detectable
HBcrAg (>2 log10 U/ml) or pg HBV RNA at time of NA therapy
withdrawal which infers ongoing HBV transcription and
may predict significant ALT flare and the need to reinstitute
therapy.

StephenW

530
可检测的Hbcrag或基因组前HBV
核苷类似物时血清中的RNA
治疗戒断预测严重的ALT突发
结果和需要重新开始治疗？
Ivana Carey1，Emily K. Butler2，Matthew Bruce1，Jeffrey
Gersch2，Bo Wang，Mary Kuhns2，Gavin Cloherty2，Geoffrey
M. Dusheiko1和Kosh Agarwal1，（1）肝脏研究所，
国王学院医院，（2）传染病研究，
雅培实验室
背景：取出核（t）ide类似物（NA）in
长期HBV抑制慢性乙型肝炎（CHB）患者
可导致某些人HBV DNA和HBsAg丢失的减少
耐心。相反，一些患者需要重新开始NA
治疗。需要预测结果
治疗后停药。两种新的血清标志物
HBV复制/转录活性 - 乙型肝炎核心相关
抗原（HBcrAg）和前基因组（pg）HBV RNA
可能会增加对预测变量结果的洞察力。目标：
评估是否定量HBsAg，HBcrAg和pg HBV
戒断NA后的RNA水平及其动力学可以预测
显着的ALT突发（ALT> 10xUNL）需要重新启动
NA疗法。方法：15例CHB HBeAg阴性，非肝硬化
患者（中位纤维素4.7kPa）抑制> 3年
替诺福韦停药时（中位数为5.1岁，范围为3.2-11.8岁）
抗病毒治疗，并在第一次每4周进行一次
6个月，然后每8周一次（中位数持续时间
52周，范围16-52周）。历史治疗
血浆样本（NUC治疗的基线，第3年，第5年和第5年）
第7年（如果可用）在治疗退出（EOT）和
在治疗后4,8,12,16,24,32和52周
集。 HBV DNA（TaqMan Roche PCR）[IU / ml]，HBsAg
（Abbott Architect）[IU / ml]，HBcrAg（CLEIA Fujirebio）[log10U /
ml]和Abbott pg HBV RNA研究分析[log10U / ml]
比较轻度ALT突发的患者（ALT> 2
x UNL并自发消退（n = 7）与患者相比
显着的ALT突发（ALT> 10 UNL，HBV DNA> 100,000 IU /
ml）（n = 3）（全部重新启动NA）与没有ALT突发的患者相比
（NA = 5）戒断NA治疗后。结果：抗病毒期间
治疗后所有患者6例后均无法检测到HBV DNA
个月; HBsAg中位数下降为每月18 IU / ml。
7/15名患者在治疗开始时可检测到HBcrAg
与EOT的1名患者相比。 HBV RNA（LOQ 1.65 log10 U / ml）为
在治疗开始时检测到12/15患者与治疗开始时检出2例患者
EOT。 EOT患者血清ALT正常（中位数）
34 IU / l）.HBV DNA，HBsAg，HBcrAg的中位数变化，
pg HBV RNA和ALT停止后治疗如图所示
图1（根据耀斑的类型呈现）。只有患者
具有显着ALT突发的可检测到的HBcrAg（> 2log10 U /
ml）或在EOT检测到pg HBV RNA。没有发生HBsAg丢失
在这个队列中。结论：67％的患者有ALT突发
撤回NA后。 20％的患者ALT升高至
> 10 x UNL和HBV DNA> 100.000 IU / ml治疗后。
具有这种程度的ALT突发的所有患者都可检测到
NA治疗时HBcrAg（> 2 log10 U / ml）或pg HBV RNA
撤回，推断正在进行的HBV转录和
可以预测显着的ALT突发和需要重建
治疗。