THU-206
HBV DNA relapse after stopping nucleoside analogue therapy in
patients with HBsAg loss: Detectable pre-genomic HBV RNA is a
better predictor of relapse than ultra-sensitive HBsAg-
‘implications for HBV cure’
Ivana Carey1, Jeffrey Gersch2, Christiana Moigboi1, Matthew Bruce1,
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 States
Email: [email protected]
Background and aims: Functional cure in chronic hepatitis B (CHB) is
defined as a loss of HBsAg, undetectable HBV DNA and absence of
ongoing liver damage. The EASL HBV guidelines recommend
consolidation therapy with nucleos (t)ide analogue (NA) for at least
6 months after achieving HBsAg loss. HBV DNA or HBsAg re-activation
is rare but markers predicting relapse are lacking. Serum pre-genomic
(pg) HBV RNA reflects cccDNA transcriptional activity, and ultrasensitive
HBsAg assay (CLEIA HBsAgHQ Fujirebio) enables HBsAg
detection at very low levels (0.5mIU/ml). We have evaluated the
ability of pgHBV RNA, ultrasensitive HBsAg and anti-HBs antibody
titre to predict HBV re-activation in patients who achieved HBsAg loss
and stopped NA therapy
Methods: 19 CHB non-cirrhotic patients (61%males, median age 43.7
yrs) were treated for a median duration 8.5 yrs (1.6-12.2) with
tenofovir (TDF) and achieved HBsAg loss after a median 7.5 yrs.
Therapy with TDF was continued for median one year (0.5-2.7 yrs)
after HBsAg loss. 12 weeks after TDF withdrawal 2 (11%) patients had
detectable HBV DNA, but not HBsAg (qualitative). PgHBV RNA was
measured by a novel real-time PCR research assay (Abbott
Diagnostics [LLDQ 1.65 log10U/ml]), ultrasensitive HBsAg by CLEIA
HBsAgHQ (Fujirebio) [LLDQ 0.5mIU/ml] and anti-HBs antibody titre
on Abbott Architect [mIU/ml]. Levels were compared between
patients according to re-activation status. In patients with reactivation
TDF therapy was re-commenced and follow-up serum
samples were available for test.
Results: Age, therapy duration overall and after achieving HBsAg loss,
ALTactivityand HBsAg levels by ultrasensitive testwere similar at TDF
withdrawal irrespective of re-activation. At the time of TDF
withdrawal all patients had detected HBsAg by ultrasensitive test
(median 1.23, range 0.6-190 mIU/ml). However, pgHBV RNA was
exclusively detected in 2 patients with re-activation (median 2.12,
range 2.01-2.23 log10U/ml, p = 0.02). Anti-HBs antibodies titres were
lower in patients with re-activation (median 0.3 vs. 3.6 mIU/ml, p =
0.01). At the first visit after TDF withdrawal patients with reactivation
had detectable HBV DNA (45600 and 12100 IU/ml), pgHBV
RNA and HBsAg levels by ultra-sensitive assay increased from
concentrations at therapy cessation. 12 weeks after re-commencing
TDF, both HBV DNA and pgHBV RNA were not detected, HBsAg
concentrations declined and anti-HBs antibodies levels increased.
Conclusion: Pre-genomic HBV RNA and anti-HBs antibodies are
helpful makers to predict sustained loss of HBsAg without a HBV DNA
increase after NA withdrawal in CHB patients who have achieved
HBsAg loss on therapy. The HBsAg ultrasensitive assay provided a
useful insight into dynamics of HBsAg changes after NA withdrawal
but did not help to predict HBV re-activation. Larger studies assessing
the utility of these markers to predict HBV re-activation after HBsAg
loss are needed.作者: StephenW 时间: 2019-4-1 07:32