EASL2020[AS093]ALT爆发后血清学反应的特征。 来自5个临床试验

StephenW

AS093
Characterization of serologic responses following ALT flares in
>3000 CHB patients pooled from 5 clinical trials
Maurizia Brunetto1, Wan-Long Chuang2, Patrick Marcellin3,
Thomas Berg4, Hongyuan Wang5, Vithika Suri5, Lanjia Lin5,
John F. Flaherty5, Anuj Gaggar5, Edward Gane6, Maria Buti7,
Kosh Agarwal8. 1Hepatology Unit, University Hospital of Pisa, Pisa, Italy;
2Hepatobiliary Division, Department of Internal Medicine, Kaohsiung
Medical University Hospital; 3Department of Hepatology, AP-HP Hôpital
Beaujon, Clichy, France; 4Department of Gastroenterology and
Rheumatology, Section of Hepatology, University Hospital Leipzig;
5Gilead Sciences Inc., Foster City, CA, USA; 6Auckland Clinical Studies,
Auckland, New Zealand; 7Hospital General Universitario Valle Hebron
and Ciberehd, Barcelona; 8Institute of Liver Studies, King’s College
Hospital
Email: [email protected]
Background and Aims: ALT flares in patients treated for Chronic
Hepatitis B (CHB) infection have been associated with improvements
in viral parameters. The timing, frequency, severityand consequences
of these elevations in ALT have not been completely characterized.
Here, we pool data from 5 Phase 3 studies evaluating tenofovir-based
regimens to determine the associations of ALT flares with different
treatment outcomes.
Method: Clinical data from 5 studies (GS-US-174-102, GS-US-174-
103, GS-US-174-0149, GS-US-320-0108, and GS-US-320-0110) were
evaluated for the presence of ALT flares on treatment, defined as ALT
>5× ULN and >2× Baseline (Low Flares) or ALT >10× ULN and >2×
Baseline (High Flares). Endpoints of HBsAg loss, HBeAg loss, and
HBsAg decline of >=1log10 were evaluated at 12, 24, or 48 weeks after
the flare.
Results: The overall populationwas 3013 patients of whom 70% were
Asian and 67% were male. Overall, 58% were HBeAg positive at
baseline and 8%, 22%, 41%, and 27% had Genotype A, B, C, and D
infection, respectively. Of these subjects, LowFlareswere observed in
297 (9.9%) subjects with High Flares observed in 141 (4.7%) patients;
the medianweek (Q1,Q3) to ALT flarewas 8 (4, 59) for lowflare and 14
(4,61) for high flare. In the overall population, HBeAg and HBsAg loss
was observed in 634 and 93 subjects, respectively, during the
treatment phase. The rates of serologic outcomes following these
flares are shown in the table. Briefly, the presence of low and high
flareswere associated with increased rates of serologic outcomes that
increased with longer duration follow-up. Rates of serologic outcomes
were observed more often in patients having higher flares,
though the higher flares identified overall fewer cases of patients
achieving the clinical endpoints. Interestingly, the majority of
patients with HBeAg loss and HBsAg loss did not have a measured
ALT flare in the preceding 48 weeks of treatment.Conclusion: Serologic outcomes of HBeAg loss and HBsAg decline
and loss occurred following on-treatment ALT flares. These data
demonstrate that the majority of patients achieved clinical endpoints
24 weeks after the ALT flare, though additional follow-up may
identify more patients achieving these endpoints. These data inform
current strategies for achieving important clinical outcomes for CHB
patients, and suggest that some patients can achieve HBsAg/HBeAg
loss without ALT flares.

StephenW

AS093
ALT爆发后血清学反应的特征。
来自5个临床试验的> 3000名CHB患者
毛里兹·布鲁内托（Maurizia Brunetto）1，庄万龙（Cong-Long）2，帕特里克·马塞林（Patrick Marcellin）3
托马斯·伯格（Thomas Berg），王宏远（Wangyuanwang）5，苏富比（Vithika Suri）5，兰嘉（Lanjia Lin），
John F.Flaherty5，Anuj Gaggar5，Edward Gane6，Maria Buti7，
柯什·阿加瓦尔8。 1意大利比萨大学医院肝病科；
2高雄市内科肝胆科
医科大学附属医院； 3 AP-HPHôpital肝病科
法国克利希博戎; 4消化内科
莱比锡大学医院肝病科风湿病科；
5Gilead Sciences Inc.，美国加利福尼亚州福斯特市； 6奥克兰临床研究，
新西兰奥克兰； 7医院普通大学瓦莱·希伯伦
还有巴塞罗那的塞伯莱德（Ciberehd）； 8金氏学院肝病研究所
医院
电子邮件：[email protected]
背景与目的：接受慢性治疗的患者出现ALT发作
乙型肝炎（CHB）感染与改善有关
在病毒参数上。时间，频率，严重性和后果
这些ALT升高中的一部分尚未完全表征。
在这里，我们汇总了5项基于替诺福韦的3期研究的数据
确定ALT耀斑与不同类型的关联的方案
治疗结果。
方法：5项研究的临床数据（GS-US-174-102，GS-US-174-
103，GS-US-174-0149，GS-US-320-0108和GS-US-320-0110）
评估治疗中是否存在ALT耀斑，定义为ALT
> 5×ULN和> 2×基线（低耀斑）或ALT> 10×ULN和> 2×
基线（高耀斑）。 HBsAg丢失，HBeAg丢失和
在第12、24或48周后评估HBsAg下降> = 1log10
耀斑。
结果：总人口为3013名患者，其中70％为
亚洲人占67％，男性。总体而言，58％的HBeAg阳性
基线，分别有8％，22％，41％和27％的基因型为A，B，C和D
分别感染。在这些受试者中，观察到了低火炬
在141（4.7％）位患者中观察到297（9.9％）位高耀斑患者；
低耀斑和ALT耀斑的中位数周（Q1，Q3）为8（4，59），而低耀斑为14
（4,61）用于高耀斑。在总体人群中，HBeAg和HBsAg丢失
分别在634名和93名受试者中观察到
治疗阶段。在这些之后血清学结果的发生率
耀斑示于表中。简而言之，低和高的存在
耀斑与血清学结果发生率增加有关，
随着随访时间的延长而增加。血清学结果率
在耀斑高的患者中更常见
尽管较高的耀斑确定总体上较少的患者病例
达到临床目标。有趣的是，大多数
HBeAg丢失和HBsAg丢失的患者未进行测量
治疗前48周出现ALT发作。结论：HBeAg丢失和HBsAg下降的血清学结果
和损失发生在治疗后的ALT爆发后。这些数据
证明大多数患者达到了临床终点
ALT发作后24周，尽管可能需要进一步随访
确定更多实现这些终点的患者。这些数据通知
实现CHB重要临床结果的当前策略
患者，并建议某些患者可以达到HBsAg / HBeAg
没有ALT发作的流失。