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PS-055
The markers of HBV transcriptional activity-HBcrAg and pregenomic
HBV DNA during antiviral therapy with nucleos (t)ide
analogue help to predict optimal timing of therapy withdrawal
Ivana Carey1, Jeffrey Gersch2, Matthew Bruce1, Christiana Moigboi1,
Bo Wang1, Mary Kuhns2, Gavin Cloherty2, Geoffrey Dusheiko1,
Kosh Agarwal1. 1Institute of Liver Studies, King’s College Hospital,
London, United Kingdom; 2Department of Infectious Diseases, Abbott
Diagnostics, Chicago, United Kingdom
Email: [email protected]
Background and aims: Nucelos (t)ide analogue (NA) withdrawal is a
potential therapeutic strategy in long-term supressed HBeAgnegative
non-cirrhotic chronic hepatitis B (CHB) patients. We
previously demonstrated in 15 patients that 20% patients had
severe post-withdrawal ALT flare (> 10 UNL) and required to restart
NA therapy. At time of NA withdrawal all patients with
significant flare after stopping NA had detectable HBcrAg and pregenomic
(pg)HBV RNA, both markers of cccDNA transcriptional
activity. Data regarding changes of HBV serological/virological
markers during NA therapy prior to NA withdrawal are lacking and
might provide valuable information about the timing of NA
withdrawal. We aimed to compare the levels of HBV DNA, HBsAg,
HBcrAg and pgHBV RNA and their kinetics during long-term NA
therapy prior to NA withdrawal to evaluate whether on-treatment
markers can help with timing of successful NA withdrawal.
Methods: We studied 25 CHB non-cirrhotic patients (64%males,
median age 48yrs) were treated for a median duration 6.9 yrs (3.2-
11.2) with tenofovir (TDF) and had undetectable HBV DNA for at least
3 years. TDF was stopped and patients were followed for at least 52
weeks (median 78, range 52-78). Based on type of ALT flare post NA
withdrawal, patientswere divided into 3 groups: no flare (n = 9), mild
ALT flare (> 2 < 5 UNL and > 2 fromNA stop baseline, n = 11) and 5 with
severe flare (> 10UNL withHBVDNA> 100, 000IU/ml). Serum samples
from NA therapy at baseline, years 1, 2 and 3 on therapy and at time
of withdrawal were tested for HBV DNA and HBsAg levels, HBcrAg
concentrations (by were CLEIA Fujirebio assay [LLDQ 2 log10U/ml])
and pgHBV RNA (using a real-time PCR research assay Abbott
Diagnostics [LLDQ 1.65 log10U/ml]). The markers were compared
between patients according to post withdrawal ALT flare status.
Results: At time of startingNA therapy patients with severe flares had
significantly higher levels of HBV DNA, HBcrAg and pgHBV RNA, but
quantitative HBsAg, ALT and degree of liver damage were similar. All
serological/virological markers declines did not differ across the
groups. By year 1 only HBcrAg and pgHBV RNA levels were higher in
patients with subsequent severe flares and this remained the case
until NA withdrawal (Figure 1). The proportions of patients withdetectable HBcrAg and pgHBV RNA reduced during NA therapy
(Figure 1); only patients who developed severe flares had detectable
HBcrAg and pgHBV RNA at time of withdrawal.
Conclusion: During NA treatment of HBeAg negative patients, serum
levels of HBcrAg and pgHBV RNA, ostensibly markers of transcriptional
cccDNA activity were strong predictors of subsequent
significant ALT flares after NA withdrawal and their monitoring on
NA therapy might assist with appropriate timing of NAwithdrawal to
avoid relapse and related disease after NA withdrawal |
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发表于 2019-3-30 15:29