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Treatment Cessation in Chronic Hepatitis
B: Predicting Off-Treatment Durability Via
Combination of Viral Markers
Wai Kay Walter Seto1, Kevin Liu2, Lung-Yi Mak3, Ka Shing
Cheung4, Danny Ka Ho Wong5, Fen Liu4, James Fung6, Ching
Lung Lai4 and Man-Fung Yuen7, (1)Queen Mary Hospital,
Hong Kong, Hong Kong, (2)Medicine, Queen Mary Hospital,
Hong Kong, (3)Queen Mary Hospital, (4)Medicine, The
University of Hong Kong, (5)State Key Laboratory for Liver
Research, The University of Hong Kong, (6)Medicine, Queen
Mary Hospital, (7)Department of Medicine, University of Hong
Kong, Queen Mary Hospital
Background: Treatment cessation in nucleoside analoguetreated
chronic hepatitis B (CHB) can be associated with high
rates of disease relapse. Serum hepatitis B surface antigen
(HBsAg) levels have been suggested as a marker reflecting
immune control. We investigated the efficacy of treatment
cessation and predictors of successful off-treatment durability
in CHB patients with low serum HBsAg levels. Methods: We
prospectively recruited consecutive non-cirrhotic HBsAgpositive
patients treated with entecavir or tenofovir with serum
HBsAg <200 IU/mL and fulfilling the European Association for
the Study of the Liver (EASL) criteria for treatment cessation.
Liver biochemistry, serum HBV DNA, HBsAg and hepatitis B
core-related antigen (HBcrAg) were measured at baseline
and every 6 weeks up to week 48 after treatment cessation.
HBV reactivation was defined as HBV DNA >2,000 IU/mL.
Treatment was re-initiated in patients with HBV reactivation
and elevated alanine aminotransferase (ALT) (>40 U/L), or
with two consecutive HBV DNA readings of >2,000 IU/mL (the
second measurement taken within two weeks). Results: In
this interim analysis, 103 patients (mean age 56.4 ±10.9 years,
67.0% male) with a mean nucleoside analogue treatment
duration of 7.1 (±2.0) years were recruited. Median duration
of follow-up after treatment cessation was 42 (IQR 29-48)
weeks. Median baseline HBsAg and HBcrAg levels were 55.3
(16.9-89.5) IU/mL and 1.1 (0.3-4.7) kU/mL respectively. The
cumulative rate of HBV reactivation at 48 weeks, calculated
by the Kaplan-Meier method, was 59.2%. Among 78 patients
with available viral measurements, baseline serum HBsAg
≤10 IUmL, compared to HBsAg >10 IU/mL, had a significantly
lower cumulative rate of HBV reactivation (31.6% versus
66.1%, p=0.023). A lower baseline serum HBsAg level, via Cox
regression, was associated with significantly lower rates of
HBV reactivation (p=0.047, OR 1.005, 95%CI 1.001-1.010). A
lower baseline serum HBcrAg level was associated with lower
HBV reactivation rates in patients with baseline serum HBsAg
>20 IU/mL (p=0.020, OR 1.034, 95%CI 1.005-1.063) but not
among all patients (p=0.147). 16 (33.3%) patients with HBV
reactivation developed ALT elevation (median ALT 104 U/L,
IQR 62-151 U/L). All HBV reactivation cases were eventually
controlled with either entecavir or tenofovir. Conclusion:
HBV reactivation remained common after treatment cessation
in HBsAg-positive patients with low HBsAg levels. Combining
serum HBsAg and HBcrAg kinetics can identify patients with
likely off-treatment durability after treatment discontinuation.
(Clinicaltrials.gov identifier NCT02738554)作者: StephenW 时间: 2018-10-18 13:54