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Peripheral and intrahepatic virological phenotyping in
eAg negative Chronic Hepatitis B underlines the limitations
of current treatment thresholds in low to moderate
viraemic patients.
Valentina Svicher1, Romina Salpini1, Upkar S. Gill2, Luna Colagrossi1,
Navjyot K. Hansi2, Carlo F. Perno1, Patrick T. Kennedy2;
1University of Rome Tor Vergata, Department of Experimental
Medicine and Surgery, Via Montpellier, Rome, Italy; 2Hepatology,
Centre for Immunobiology, Blizard Institute, Barts and The London
SMD, QMUL, London, United Kingdom
INTRODUCTION: Persistence of HBsAg is associated with an
increased risk for the development of HCC in chronic hepatitis
B (CHB) and quantitative HBsAg (qHBsAg) has been proposed
to risk stratify inactive carriers for disease progression and the
development of HCC. Limited data exist on the intrahepatic
compartment and how accurately qHBsAg reflects intrahepatic
total HBV DNA and cccDNA. Here we studied liver tissue from
eAg negative (eAg-) CHB patients, with 3 distinct disease profiles
based on serum HBV DNA: inactive carriers (IC), moderate
and high viral loads (VL). PATIENTS & METHODS: To
detect virological differences between the peripheral and intrahepatic
compartments, we quantified HBV DNA and HBsAg in
serum and intrahepatic total-HBV DNA (itHBV DNA) along with
cccDNA in biopsy specimens (n=43). itHBV DNA, was quantified
using a modification of the commercially available assay
for HBV DNA (COBAS® TaqMan® HBV Test, v2.0, Roche)
and cccDNA by TaqMan Real-Time assay (LightCycler2.0).
Patients were divided as follows: inactive disease, HBV DNA
<2,000IU/ml (n=15): Group 1; moderate VL; HBV DNA
2,000-20,000IU/ml (n=9): Group 2; and high VL, HBV DNA
>20,000IU/ml (n=19): Group 3. Data on longitudinal ALT,
Ishak fibrosis stage and necroinflammatory (NI) scores were
documented to establish clinical correlations and determine
any difference between the groups. RESULTS: Patients in each
group were age matched; median (IQR) age of 31 (27-41);
with no difference in ALT, Ishak fibrosis stage and NI score.
Overall, itHBV DNA positively correlated with serum HBV DNA
and qHBsAg (Rho=0.71; p=<0.0001 & Rho=0.43; p=0.008
respectively). Conversely, cccDNA only positively correlated
with serum HBV DNA (Rho=0.35, p=0.04), but not qHBsAg
(p=0.6), suggesting the lack of a direct relationship between
the HBV genomic reservoir and transcriptional activity of the
sAg gene in eAg- disease. No difference was noted between
itHBV DNA and cccDNA in Group 1 vs. Group 2 (p=0.74 &
p=0.28 respectively), but significantly higher levels detected
in Group 3 vs. Group 1 & 2 (p<0.001 & p=0.017 respectively).
Conversely, qHBsAg was similar between all groups,
suggesting substantial sAg production even in the presence
of a lower genomic reservoir. CONCLUSIONS: These data
show that patients defined as ICs based on clinical parameters
and those with HBV DNA up to 20,000IU/ml have a similar
HBV genomic reservoir, that differs significantly from those
with HBV DNA >20,000IU/ml. The comparable amount of
qHBsAg underlines the potential for disease progression and
HCC development. Better characterisation of low and moderate
viraemic eAg- CHB is needed to inform long-term clinical
management.
Disclosures:
Valentina Svicher - Grant/Research Support: bms; Speaking and Teaching: bms,
gilead
Romina Salpini - Speaking and Teaching: BMS
Patrick T. Kennedy - Grant/Research Support: Gilead; Speaking and Teaching:
Roche, BMS, Roche, Gilead
The following people have nothing to disclose: Upkar S. Gill, Luna Colagrossi,
Navjyot K. Hansi, Carlo F. Perno
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发表于 2016-10-19 16:05
