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HBsAg LOSS IN INACTIVE CHRONIC HEPATITIS B CARRIERS
IS DEPENDENT ON LEVEL OF QHBSAG AND INTERFERON
RESPONSE: A RANDOMISED CONTROL TRIAL
Seng Gee Lim1,2,3, Guan Huei Lee4, Yock Young Dan5,
Yin Mei Lee4, Poh Seng Tan2, Wah Wah Phyo3, Htet Htet
Toe Wai Khine3, Karen De Lunas4, Chris Lee3, Amy Tay3,
Cindy Seah6 and Edwin Chan7,8, (1)Gastroenterology &
Hepatology, National University Health System, (2)Division
of Gastroenterology and Hepatology, National University
Health System, Singapore, (3)Dept of Medicine, Yong Loo
Lin School of Medicine, (4)Division of Gastroenterology &
Hepatology, National University Health System, (5)Division
of Gastroenterology & Hepatology, National University
Health System, Singapore, (6)Division of Gastroenterology
and Hepatology, National University Health System, (7)
Epidemiology, Singapore Clinical Research Institute, (8)
Duke-Nus School of Medicine
Background: Retrospective analysis of peginterferon therapy
of Chronic Hepatitis B (CHB) carriers suggests a high rate of
HBsAg loss, but this has not been examined in a prospective
randomised control trial(RCT) Methods: We conducted a three
arm RCT of peginterferon alpha2a (PEG)(pegasys, Roche)
180mcg weekly randomised 1:1:1 to 24 weeks(PEG24), 48
weeks(PEG48) or no treatment(C) in CHB carriers in a single
centre study (clinicaltrials.gov:NCT02992704). Patients were
randomly assigned by computer generated code based
on: HBsAg(+)>6months, HBeAg(-), normal ALT, HBV DNA
≤2x104IU/ml or qHBsAg≤1000IU/ml; absence of cirrhosis,
treatment naive, absence of HCV/HDV/HIV coinfection. The
primary endpoint was HBsAg loss 24weeks after treatment,
and study size of 90 patients had 80% power to detect a 25%
difference between any PEG arm and control Data analysis
was performed using SPSSv20 based on ITT analysis
Baseline and on-treatment variables and multivariate
analysis were used to predict HBsAg loss Results: Baseline
characteristics were similar between groups HBsAg loss
occurred in a total of 7/30 (23 3%) in PEG48, 9/30 (30%) in
PEG24 and 1/30(3 3%) in C Baseline predictors of HBsAg
loss at end-of-interferon treatment showed that qHBsAg
<71IU/ml had an AUROC 0 883; when baseline and ontreatment
predictors were assessed by multivariate analysis,
baseline qHBsAg logIU/ml (OR 10 82, 95%CI 1 02-114 58)
and >1log reduction in qHBsAg at week 12 (OR 11.29, 95%
CI 1 48-86 33) were the strongest predictors of HBsAg loss
There were three distinct patterns of interferon response
despite qHBsAg<71IU/ml: Responders (HBsAg loss) had a
mean qHBsAg log IU/ml reduction at week 24 of 1 46, partial
responders had mean qHBsAg log IU/ml reduction of 0 65
non-responders had mean qHBsAg log IU/ml increase at
week 24 of 0 1 There were a total of 282 adverse events
most of which were interferon related(90%) There were 4
Serious Adverse Events where one was related to treatment
due to hospitalisation from hypothyroidism related to
interferon There were no deaths in the study Conclusion:
HBsAg loss with PEG in inactive carriers leads to 20-30%
HBsAg loss but interferon responsiveness was the main
factor driving HBsAg loss in low qHBsAg patients This has
implications for new immunomodulator therapies that rely on
interferon responsiveness such as TLR7, TLR8 and RIG-I
agonists. 作者: StephenW 时间: 2019-10-24 20:14