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AS093
Characterization of serologic responses following ALT flares in
>3000 CHB patients pooled from 5 clinical trials
Maurizia Brunetto1, Wan-Long Chuang2, Patrick Marcellin3,
Thomas Berg4, Hongyuan Wang5, Vithika Suri5, Lanjia Lin5,
John F. Flaherty5, Anuj Gaggar5, Edward Gane6, Maria Buti7,
Kosh Agarwal8. 1Hepatology Unit, University Hospital of Pisa, Pisa, Italy;
2Hepatobiliary Division, Department of Internal Medicine, Kaohsiung
Medical University Hospital; 3Department of Hepatology, AP-HP Hôpital
Beaujon, Clichy, France; 4Department of Gastroenterology and
Rheumatology, Section of Hepatology, University Hospital Leipzig;
5Gilead Sciences Inc., Foster City, CA, USA; 6Auckland Clinical Studies,
Auckland, New Zealand; 7Hospital General Universitario Valle Hebron
and Ciberehd, Barcelona; 8Institute of Liver Studies, King’s College
Hospital
Email: [email protected]
Background and Aims: ALT flares in patients treated for Chronic
Hepatitis B (CHB) infection have been associated with improvements
in viral parameters. The timing, frequency, severityand consequences
of these elevations in ALT have not been completely characterized.
Here, we pool data from 5 Phase 3 studies evaluating tenofovir-based
regimens to determine the associations of ALT flares with different
treatment outcomes.
Method: Clinical data from 5 studies (GS-US-174-102, GS-US-174-
103, GS-US-174-0149, GS-US-320-0108, and GS-US-320-0110) were
evaluated for the presence of ALT flares on treatment, defined as ALT
>5× ULN and >2× Baseline (Low Flares) or ALT >10× ULN and >2×
Baseline (High Flares). Endpoints of HBsAg loss, HBeAg loss, and
HBsAg decline of >=1log10 were evaluated at 12, 24, or 48 weeks after
the flare.
Results: The overall populationwas 3013 patients of whom 70% were
Asian and 67% were male. Overall, 58% were HBeAg positive at
baseline and 8%, 22%, 41%, and 27% had Genotype A, B, C, and D
infection, respectively. Of these subjects, LowFlareswere observed in
297 (9.9%) subjects with High Flares observed in 141 (4.7%) patients;
the medianweek (Q1,Q3) to ALT flarewas 8 (4, 59) for lowflare and 14
(4,61) for high flare. In the overall population, HBeAg and HBsAg loss
was observed in 634 and 93 subjects, respectively, during the
treatment phase. The rates of serologic outcomes following these
flares are shown in the table. Briefly, the presence of low and high
flareswere associated with increased rates of serologic outcomes that
increased with longer duration follow-up. Rates of serologic outcomes
were observed more often in patients having higher flares,
though the higher flares identified overall fewer cases of patients
achieving the clinical endpoints. Interestingly, the majority of
patients with HBeAg loss and HBsAg loss did not have a measured
ALT flare in the preceding 48 weeks of treatment.Conclusion: Serologic outcomes of HBeAg loss and HBsAg decline
and loss occurred following on-treatment ALT flares. These data
demonstrate that the majority of patients achieved clinical endpoints
24 weeks after the ALT flare, though additional follow-up may
identify more patients achieving these endpoints. These data inform
current strategies for achieving important clinical outcomes for CHB
patients, and suggest that some patients can achieve HBsAg/HBeAg
loss without ALT flares.
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