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s 458D
Association of Circulating Hepatitis B Virus
(HBV) Biomarkers with HBsAg Loss and
Absence of Re-Treatment after Discontinuation
of Long Term Treatment with Tenofovir (DF) in
HBeAg Negative Patients in the Finite Study
Florian van Bömmel1, Alena Van Bömmel2, Danilo Deichsel1,
Maria Pfefferkorn1, Christin Felkel1, Janett Fischer1, Sandra
Krohn1, Karen Rother1, Jessica Wacker3, Martin Brehm3,
Rainer Dannenberg3, Anuj Gaggar4, William E. Delaney5,
Andrea Cathcart4 and Thomas Berg1, (1)Department of
Gastroenterology and Rheumatology, Section of Hepatology,
University Hospital Leipzig, (2)Max Planck Institute for
Molecular Genetics, (3)Mvz Labor Dessau Gmbh, (4)
Gilead Sciences, Inc, Foster City, California, USA, (5)Gilead
Sciences, Inc.
Background: Following > 4 years of treatment with tenofovir
disoproxil fumarate (TDF), 42 patients were randomized (1:1)
to either continue or discontinue TDF and followed for 144
weeks (FINITE study). In the discontinue arm, HBsAg loss had
occurred in 4/21 patients and 8 patients required re-treatment.
We aimed at investigating the association of circulating HBV
biomarkers with HBsAg loss and need for re-treatment after
TDF discontinuation. Methods: A total of 210 serum samples
stored at -20°C collected from 42 patients at weeks 12, 24,
36 and 48 after TDF discontinuation was analyzed. Levels
of HBV DNA, HBsAg, components of HBsAg, HBV RNA and
HBcrAg and were quantified by either real time PCR (Roche,
LOD 6IU/mL), ELISA (Abbott Architect, LOD 0.5 IU/mL),
ELISA (LHBs, LOD=0.03ng/mL; MHBs, LOD=0.47ng/mL;
SHBs/total HBsAg, LOD=0.08ng/mL; HBsAg 6.0, Enzgnost,
Siemens), specific real-time PCR (LOD 800 copies/mL) or
ELISA (Fujirebio, LOD 2 log10IU/mL), respectively. End points
were HBsAg loss or re-treatment with TDF by week 144.
Results: Absence of re-treatment was associated with lower
mean HBcrAg levels at baseline (3.2±1.4 (3-3.9) vs. 3.7±1.6
(3-7.5) log10 U/mL; p=0.019), higher ratios of SHBs (83 (79-88)
vs. 92 (82-100);p=0.007), lower increases in mean HBV DNA
(2.4±0.9 (1.3-4.2) vs. 4.7±1.7 (2.5-7.8) log10 IU/mL; p=0.003)
and HBV RNA (1.2±1.3 (0-1.3) vs. 2.7±2.6 (0-6.3) log10 c/mL;
p=0.005) at week 12. Patients with HBsAg loss showed a lower
increase in mean HBV DNA at weeks 12 (1.7±0.4 (1.3-2.2)
vs. 3.7±1.6 (1.3-7.8); p=0.008) and 24 (1.8±0.6 (1.3-2.6) vs.
3.3±1.1 (2-5.1); p=0.011) and lower mean HBsAg at baseline
(3.7±0.7 (2.7-4.2) vs. 4.5±0.6 (2.7-5.3); p=0.019), weeks 12
(3.0±0.8 (2.1-3.6) versus 4.6±0.7 (2.1-3.6); p=0.0082) and
24 (1.8±1.2 (0.2-3.2) versus 4.4±0.7 (2.7-5.3) log10 IU/mL;
p=0.0034) and there was a trend towards lower MHBs ratios
at all time points. HBV RNA was undetectable by week 12
in all patients with and in 8/17 patients without HBsAg loss
(p=0.031). Patients who continued TDF treatment showed no
changes in HBV biomarkers at all time points. Conclusion:
Lower levels of HBcrAg before TDF discontinuation as well
as the kinetics of, HBV DNA, HBV RNA and SHBs were
associated with treatment free follow up and HBsAg levels
at baseline and during follow up as well as HBV DNA kinetics
with subsequent HBsAg loss. Interestingly, HBV DNA and
HBV RNA relapses following TDF discontinuation were
significantly greater in those patients without response. Our
findings need to be validated in larger cohorts |
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发表于 2018-10-23 15:33