PS-056
Higher relapse and retreatment rates in patients who started as
HBeAg positive than negative after stopping long-term nucleos (t)
ide analogue therapy: results from the randomized controlled
STOP study
Seng Liem1,2, Scott Fung1, David Wong1, Colina Yim1, Jenny Chen1,
Seham Noureldin1, Jordan Feld1,3, Bettina Hansen1,2,4, Harry Janssen1.
1University Health Network, Toronto Centre for Liver Disease, Toronto,
Canada; 2Erasmus University Medical Center Rotterdam, Department of
Gastroenterology and Hepatology, Rotterdam, Netherlands;
3McLaughlin-Rotman Centre for Global Health, Toronto, Canada;
4University of Toronto, Institute of Health Policy, Management and
Evaluation, Toronto, Canada
Email: [email protected]
Background and aims: Patients with chronic hepatitis B (CHB) often
receive long-term nucleos (t)ide analogue (NA) therapy. We compared
outcomes after stopping NA therapy between patients who
started therapy HBeAg positive or negative.
Method: In this prospective single-center randomized controlled
trial, patients were included if they had received tenofovir/entecavir
therapy for ≥ 12 months and achieved virologic suppression (HBeAg
seroconversion and undetectable HBV DNA ≥ 12 months in HBeAg
positive patients, or undetectable HBV DNA ≥ 36 months in HBeAg
negative patients). Patients were randomized 2:1 to either stop or
continue NA therapy for 72 weeks. Retreatment criteriawere: HBeAg
seroreversion, HBV DNA > 20, 000IU/ml twice or HBV DNA > 2, 000
with ALT > 5xULN twice. Sustained response (HBeAg negative, HBV
DNA < 2, 000 IU/ml and normal ALT) was determined at week 72.Results: Of 67 patients (60% male, 97% Asian), 45 (67%) patientswere
assigned to stop and 22 (33%) to continue NA therapy. At start of
therapy, 18/45 (40%) stop patients were HBeAg positive. At randomization
the mean duration of NA therapy was 8 (3) vs. 7 (3) years, 82%
vs. 100% was anti-HBe positive and HBsAg level was 3.2 (0.9) vs. 3.0
(0.6) log IU/ml in HBeAg positive vs. negative patients. Time since
HBeAg loss was 3.8 (2.3) in patients who started therapy as HBeAg
positive. Sustained response was observed in 3/18 (17%) HBeAg
positive vs. 7/27 (26%) negative patients (p = 0.35) (Table). HBsAg loss
occurred in 1 HBeAg-negative patient.
Among patients who stopped, the mean HBsAg change from
randomization to week 72 was −0.1 (0.4) vs. 0.2 (0.2) log IU/ml in
HBeAg positive vs. negative patients (p = 0.10). 11/18 (61%) of the
HBeAg positive vs. 5/27 (19%) HBeAg negative patientswere retreated
by week 72 (p < 0.005). ALT > 1/2/5/10xULN occurred in 89/72/61/
50% vs. 70/48/37/15 % of HBeAg positive vs. negative stop patients.
One HBeAg positive patient developed a bilirubin of 68umol/L, but
none decompensated or died.
Start of therapy
Week 72 outcomes (%)
HBeAg
positiven = 27
HBeAg
negativen = 18 P
Sustained response 17 26 0.35
HBsAg loss 0 4 -
ALT > 5xULN 61 37 0.26
ALT > 10xULN 50 15 0.03
Virologic reactivation (lone
HBV DNA > 20, 000 IU/ml)
83 56 0.14
Clinical relapse (HBV DNA >
2, 000 IU/ml +ALT > 1.5xULN)
6 19 0.10
Conclusion: Start of therapy HBeAg positive patients were more
likely to relapse and receive retreatment than HBeAg negative
patients. These findings in an Asian majority cohort suggest that
patients do not benefit from stopping long-term NA therapy,
particularly those who are HBeAg positive at the start of therapy.作者: StephenW 时间: 2019-3-30 19:31