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268
Limited Sustained Response and Lack of HBsAg
Decline after Stopping Long-Term Nucleos(t)
Ide Analogue Therapy in Hbeag Negative
Patients with Chronic Hepatitis B: Results of a
Prospective, Randomized, Open-Label Phase IV
Trial
Kin Seng Liem1,2, Scott K. Fung3, David KH Wong1, Colina
K. Yim1, Seham Noureldin1, Feng Fei Huang1, Hemant A.
Shah1, Jordan J. Feld1,4, Bettina E. Hansen1,5,6 and Harry L.
A. Janssen1, (1)Toronto Centre for Liver Disease, University
Health Network, (2)Dept. of Gastroenterology & Hepatology,
Erasmus University Medical Center Rotterdam, (3)University
of Toronto, Toronto, on, Canada, (4)Mclaughlin-Rotman
Centre for Global Health, (5)Institute of Health Policy,
Management and Evaluation, University of Toronto, (6)
Department of Gastroenterology & Hepatology, Erasmus
Medical Centre Rotterdam
Background: Chronic hepatitis B (CHB) patients often
receive life-long therapy with nucleos(t)ide analogues (NA). In
this prospective randomized controlled trial we assessed the
proportion of patients with sustained response after stopping
long-term entecavir (ETV) or tenofovir (TDF) therapy.
Methods: Patients at the Toronto Centre for Liver Disease
were included if they had received ETV/TDF therapy for ≥1
year and achieved virologic suppression (defined as HBeAg
seroconversion combined with undetectable HBV DNA ≥ 12
months in HBeAg positive patients, or undetectable HBV DNA
≥ 36 months for start of therapy HBeAg negative patients).
Patients were then randomized 2:1 to stop or continue NA
therapy for 72 weeks. Patients were retreated in case of
persistent HBV DNA>20,000IU/mL, HBeAg seroreversion
or HBV DNA>2,000 with ALT>5xULN (clinical relapse).
Sustained response (HBeAg-negative, HBV DNA <2,000 IU/
mL and normal ALT) at 48 weeks of follow-up was evaluated
in both groups. Results: Of 67 enrolled patients (60% male,
97% Asian), 45 (67%) patients were randomized to stop and
22 (33%) to continue NA therapy. 37/67 (55%) patients lost
HBeAg on NA therapy. At randomization the mean duration of
NA therapy was 8 (4) years and HBsAg level was 3.0 (0.7) log
IU/mL. Sustained response was observed in 11/45 (24%) stop
vs. 22/22 (100%) continue patients at week 48 (see Figure).
Within the stop group 24/45 (53%) patients continued to have
a normal ALT and HBeAg negative status. Fourteen (21%)
patients developed ALT >10x ULN and another 7 (10%) had
ALT >5x ULN. HBsAg loss occurred in two patients (1 per
group). Mean HBsAg decline from randomization to week
48 was 0.1 (0.0-0.3) vs. 0.0 (0.0-0.1) log IU/mL in stop vs.
continue patients (p=0.50) and was not associated with peak
ALT values after stopping (p>0.05). Among patients who
stopped, 13/45 (29%) required retreatment by week 48 (6 had
virologic relapse >20,000IU/mL and 7 had clinical relapse, of
which 1 had HBeAg seroreversion). Median (range) time to
retreatment was 12 (10-30) weeks. No patient experienced
liver decompensation or died. Conclusion: Forty-eight weeks
after stopping NA therapy, only 24% of patients had a sustained
response, while 74% had relapse and 2% had HBsAg loss.
HBsAg levels in the stop group declined marginally and were
not different from the NA continuation group. The findings of
this prospective study in mainly Asian patients demonstrate
no additional benefit of stopping NA therapy. Week 72 results
will be presented at the Meeting. |
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