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. 作者: StephenW 时间: 2018-4-5 14:17