EASL 2018 FRI-322 新的标记物预测慢性乙型肝炎中HBs抗原血清学

StephenW

EASL 2018 FRI-322
Novel markers predict HBs-antigen seroclearance in chronic
hepatitis B patients from the SWAP clinical trial
W.W. Phyo1, G. Cloherty2, E. Butler2, M. Kuhns2, A. Mcnamara2,
V. Holzmayer2, J. Gersch2, W.L. Yang3, P.E.J. Chang4, J. Tan5,
A. Taufique6, Y.Y. Dan1, Y.M. Lee1, G.H. Lee1, P.S. Tan1, C.Y. Tan1,
Y.W.C. Lee1, Y.L.A. Tay1, E. Chan7, S.G. Lim1. 1National University Health
System Singapore; 2Abbott diagnostics; 3Tan Tock Seng Hospital
Singapore; 4Singapore General Hospital; 5Changi General Hospital
Singapore; 6Khoo Teck Puat Hospital Singapore; 7Singapore Clinical
Research Institute
Email: [email protected]
Background and Aims: The utility of novel markers to predict HBsAg
loss in Chronic Hepatitis B (CHB) patients have not been compared. In
this study, quantitative(q) measurements of HBsAg, HBeAg, HBV
core-related antigen (crAg) and HBV RNAwere evaluated in a clinical
trial of CHB patients.
Method: 111 patients from a randomised control trial of continuing
nucleos(t)ide analogues (NA) were compared to add-on or switch-to
peginterferon alpha 2b for 48 weeks (wk) 1:2:2 (clinicaltrial.gov
NCT01928511), with primary endpoint evaluation after 24 wk followup
(wk 72). Serum samples were tested with a research HBV RNA
assay (log U/ml); qHBeAg, qHBsAg(logIU/ml), and an ultrasensitive
HBsAg research assay (sensitivity 0.005IU/ml) (m2000 and
ARCHITECT, Abbott Laboratories); and crag (log U/ml; Lumipulse,
Fujirebio; HBeAg(-) samples only). Analysis of results was performed
with SPSS v20.
Results: 42 patients were in add-on, 46 in switch and 23 in control
arms respectively at study completion (wk 72). Baseline (bsl)
demographics: mean age 50 years, males 85%, HBV DNA(-) 100%,
and HBeAg(+) 31.5%. At end of study, 13(11.7%) patients achieved
HBsAg loss (only interferon-treated); 12/13 were HBeAg(-) at bsl.
HBsAg loss patients had lower levels of qHBsAg at bsl [1.3 ± 1.1 vs 3.0
± 0.7 (p < 0.001)], wk 12 [0.3 ± 0.9 vs 2.9 ± 0.8 (p < 0.001)] and wk 24
[0.1 ± 0.6 vs 2.8 ± 0.9 (p < 0.001)]. Patients with HBsAg loss whowere
bsl HBeAg(-) had lower crAg levels at bsl [3.2 ± 0.3 vs 3.9 ± 0.9 (p =
0.005)], wk 12 [3.2 ± 0.4 vs 3.9 ± 0.9 (p = 0.007)], and wk 24 [3.1 ± 0.2
vs 3.9 ± 0.9 (p = 0.003)]. HBV RNA(-) at wk 24 was also associated
with HBsAg loss (61.5% vs 14.3%, p < 0.001). In multivariate analysis
adjusted for age, gender, duration of prior NUC treatment and bsl
qHBsAg, qHBsAg < 2.0logIU/ml at wk 12 was an independent
predictor of HBsAg loss(OR 39.1, 95% CI 1.7–901.5, p = 0.022), with
AUROC of 0.96 (96% CI 0.9–1.0, p < 0.001). Other independent
predictors were HBV RNA(-) at wk 24[OR 10.6,95% CI 2.8–40.9, p =
0.001] and crAg(-) (<3logU/ml) at wk 12 [OR 6.8 95% CI 1.3–35.5, p =
0.022, AUROC 0.75 (95%CI 0.6–0.9)]. Overall, 24/48 HBsAg(-) samples
tested with the ultrasensitive HBsAg research assay were HBsAg(+).
None of the specific treatment arms were associated with significant
changes in qHBsAg, crAg or HBV RNA that were related to HBsAg loss.
Conclusion: QHBsAg and undetectable crAg at wk 12 and undetectable
HBV RNA at wk 24 are important predictors of HBsAg
seroclearance.

StephenW

EASL 2018 FRI-322
新的标记物预测慢性乙型肝炎中HBs抗原血清学清除
来自SWAP临床试验的乙型肝炎患者
W.W。 Phyo1，G.Cloherty2，E.Butler2，M.Kuns2，A.Mcnamara2，
V. Holzmayer2，J. Gersch2，W.L. Yang3，P.E.J. Chang4，J. Tan5，
A. Taufique6，Y.Y. Dan1，Y.M. Lee1，G.H. Lee1，P.S. Tan1，C.Y. Tan1，
Y.W.C. Lee1，Y.L.A. Tay1，E. Chan7，S.G. Lim1。 1国立大学卫生
系统新加坡; 2Abbott诊断; 3Tan Tock Seng医院
新加坡;新加坡总医院;昌吉总医院
新加坡;新加坡6Khoo Teck Puat医院; 7新加坡临床
研究机构
电子邮件：[email protected]
背景和目标：新型标志物预测HBsAg的效用
没有比较慢性乙型肝炎（CHB）患者的损失。在
本研究定量（q）测量HBsAg，HBeAg，HBV
核心相关抗原（crAg）和HBV RNA在临床中评估
CHB患者的试验。
方法：111例患者来自一项随机对照试验
将核苷（t）同类物（NA）与添加物或转换物进行比较
聚乙二醇干扰素α2b治疗48周（wk）1：2：2（clinicaltrial.gov
NCT01928511），随访24 wk后进行主要终点评估
（72周）。用研究HBV RNA测试血清样品
测定（log U / ml）; qHBeAg，qHBsAg（logIU / ml）和超灵敏
HBsAg研究分析（灵敏度0.005IU / ml）（m2000和
ARCHITECT，雅培实验室）;和岩（日志U /毫升; Lumipulse，
Fujirebio公司;仅HBeAg（ - ）样品）。对结果进行分析
与SPSS v20。
结果：附加组42例，开关组46例，对照组23例
学习完成后（72周）。基线（bsl）
人口统计学：平均年龄50岁，男性85％，HBV DNA（ - ）100％
和HBeAg（+）31.5％。研究结束时，13名（11.7％）患者达到
HBsAg消失（仅干扰素治疗）; 12/13是bsl的HBeAg（ - ）。
HBsAg丢失患者bsl的qHBsAg水平较低[1.3±1.1比3.0
±0.7（p <0.001）]，第12周[0.3±0.9与2.9±0.8（p <0.001）]和第24周
[0.1±0.6 vs 2.8±0.9（p <0.001）]。 HBsAg消失的患者
bsl HBeAg（ - ）在bsl时的crAg水平较低[3.2±0.3 vs 3.9±0.9（p =
0.005）]，第12周[3.2±0.4与3.9±0.9（p = 0.007）]和第24周[3.1±0.2
vs 3.9±0.9（p = 0.003）]。第24周的HBV RNA（ - ）也与之相关
HBsAg消失（61.5％比14.3％，p <0.001）。在多变量分析中
调整年龄，性别，先前NUC治疗和bsl的持续时间
在第12周qHBsAg，qHBsAg <2.0logIU / ml是独立的
预测HBsAg消失（或39.1,95％CI 1.7-901.5，p = 0.022），与
AUROC为0.96（96％CI 0.9-1.0，p <0.001）。其他独立
预测因子在第24周时为HBV RNA（ - ）[OR 10.6,95％CI 2.8-40.9，p =
0.001]和12周时的crAg（ - ）（<3logU / ml）[OR 6.8 95％CI 1.3-35.5，p =
0.022，AUROC 0.75（95％CI 0.6-0.9）]。总体而言，24/48 HBsAg（ - ）样品
用超敏HBsAg研究分析测试了HBsAg（+）。
没有一个特定的治疗组与重要的相关
与HBsAg消失有关的qHBsAg，crAg或HBV RNA的变化。
结论：第12周QHBsAg和检测不出crAg并且检测不到
第24周的HBV RNA是HBsAg的重要预测指标
血清清除。