标题: HBsAg降低至<1 IU / mL期间的转氨酶耀斑与 基于NAP的联合治疗 [打印本页] 作者: StephenW 时间: 2019-12-27 11:51 标题: HBsAg降低至<1 IU / mL期间的转氨酶耀斑与 基于NAP的联合治疗
Oral Abstract O3
Transaminase flares during HBsAg reduction to < 1 IU/mL are correlated with the
establishment of functional cure of HBV following NAP-based combination therapy
Andrew Vaillant,
Replicor Inc, Montreal Canada
(on behalf of the REP 301-LTF and REP 401 study authors)
Background: Nucleic acid polymers (NAPs) inhibit the assembly and secretion of HBV subviral
particles and interact with small and large forms of the hepatitis delta antigen. An analysis of all
52 participants in the REP 301 and REP 401 studies was conducted to examine the correlation
between HBsAg clearance, transaminase flares and therapeutic outcome for HBV (rebound,
virologic control or functional cure) reported for these studies.
Methods: All 52 participants from the REP 301 (NCT02233075, currently in extended follow-up
in the REP 301-LTF study, NCT02876419) and REP 401 (NCT02565719) were included.
Variables analyzed included on therapy HBsAg and anti-HBs response, maxima and area under
the curve (AUC) for ALT, AST and GGT, baseline characteristics, and therapeutic outcomes
(based on 48-week follow-up in the REP 401 study and 2-year follow-up in the REP 301-LTF
study). Virologic control of HBV is defined as HBV DNA ≤ 2000 IU/mL with normal ALT ≥ 24
weeks off therapy. Functional cure of HBV is defined as HBV DNA target not detected, HBsAg
< LLOQ and normal ALT ≥ 24 weeks off therapy.
Results: Outcomes were balanced between rebound, virologic control and functional cure
(p=0.750) and independent of baseline characteristics (p≥0.274). Transaminase flares occurred
in 96% of participants, were otherwise asymptomatic with unaltered liver function throughout
(normal bilirubin, INR and albumin) and normalized during follow-up in 81% of participants.
The incidence (p=0.733) and magnitude (p≥0.189) of flares were similar between outcomes and
independent from baseline characteristics or anti-HBs titers during therapy. Transaminase
maxima or AUC during therapy were significantly correlated with HBsAg reductions > 3 log
10 from baseline (p<0.05)
Transaminase elevations (maxima and AUC) during different thresholds of HBsAg clearance (<
1000, < 100, < 10 and < 1 IU/mL) were analyzed and were significantly greater in the virologic
control and functional cure groups (p<0.05) at all thresholds. However, the prevalence of flares
in virologic control and rebound outcome groups declined at lower HBsAg thresholds and the
presence of flares while HBsAg was < 1 IU/mL was significantly more selective for functional
cure (see table below).
Conclusions: Transaminase flares during NAP therapy occur regardless of outcome and are
well tolerated, with intensity correlated with HBsAg decline > 3 log10 from baseline. Increased
strength of transaminase flare activity, and its occurrence during HBsAg declines to < 1 IU/mL
may be important for the establishment of functional cure of HBV.作者: StephenW 时间: 2019-12-27 11:51