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P0667
INTERRUPTION OF NUCLEOS(T)IDE ANALOGUE THERAPY FOR
HBeAg-NEGATIVE CHRONIC HEPATITIS B – A NEW CONCEPT
TO ACHIEVE HBsAg DECLINE?
C. Hoener Zu Siederdissen1, F. Rinker1, C. Falk2, N. Filmann3,
B. Maasoumy1, K. Deterding1, K. Port1, C. Mix1, E. Herrmann3,
H. Wedemeyer1, M.P. Manns1, A. Kraft1, M. Cornberg1. 1Department
of Gastroenterology, Hepatology and Endocrinology, 2Institute
of Transplant Immunology, Hannover Medical School, Hannover,
3Institute of Biostatistics and Mathematical Modeling, Faculty of
Medicine, Goethe-University, Frankfurt am Main, Germany
E-mail: [email protected]
Background and Aims: HBsAg loss during treatment with
nucleos(t)ide analogues (NA) is a rare event. Thus, treatment
duration with NA is usually not finite and stopping rules before
HBsAg loss are not clearly defined, especially in HBeAg-negative
patients.
Methods: In a prospective pilot trial, we stopped NA treatment in 15
patients with HBeAg-negative chronic hepatitis B. Inclusion criteria
were ongoing antiviral treatment with NA and suppressed HBVDNA
<20 IU/ml for at least 3 years as well as HBsAg <3500 IU/ml. Patients
with co-infection, other concomitant liver disease, liver cirrhosis
and immunosuppressive therapy were excluded. All patients had an
indication for antiviral treatment at the time point of NA initiation
according to international guidelines. At every visit, patients were
assessed for virological relapse, defined by HBVDNA >2000 IU/ml.
Quantitative HBsAg levels one year before and after treatment
cessation were compared to assess differences in HBsAg levels.
Serum IP-10 (CXCL10) levels of 13 patients were analysed using
multiplex technology (BioRad Bio-Plex-System).
Results: So far, complete data are available for 13 patients
with one year follow-up (FU). Virological relapse after treatment
cessation was detected in 4 patients (31%) at week 4, in 7
patients (54%) at week 8 and in 1 patient at week 24. No
virological relapse occurred in 1 patient. Interestingly, IP-10 levels
were significantly enhanced at week 8 after stop of NA therapy
(p = 0.028). Two patients developed an ALT flare >5 ULN during FU
but no patient showed signs of liver failure or significant increase
of bilirubin. In 11/12 patients with virological relapse treatment
was re-initiated with either entecavir or tenofovir and HBV-DNA
was successfully suppressed at week 48 follow-up. Importantly,
longitudinal monitoring before/after cessation showed a significant
decline in median HBsAg levels from stop of NA therapy to 48 week
FU (p = 0.0012) while there was no change during NA therapy one
year before treatment cessation.
Conclusions: Treatment cessation in non-cirrhotic patients with
HBeAg-negative chronic hepatitis B is safe but leads to virological
relapse in >90% until week 24. Stop of NA therapy was associated
with an induction of serum IP-10 that may help to explain the effect
on HBsAg decline. Thus interrupting NA treatment and inducing
immune responses should be further investigated as an option to
facilitate HBsAg loss
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发表于 2015-5-24 17:58