studies

574A AASLD ABSTRACTS HEPATOLOGY, October, 2015
mately 10 hours (Day -1) and 2 hours (Day 1) prior to SD 100
mg GZR/50 mg EBR FDC on Day 1. In Period 3, 40 mg PAN
was administered QD on Days 1 to 5 followed by administration
of SD 100 mg GZR/50 mg EBR FDC 2 hours after PAN
administration on Day 5. There was at least a 10-day washout
between periods. PK parameters were determined for GZR and
EBR on Day 1 of Periods 1 and 2, and on Day 5 of Period 3.
Results Coadministration of FAM 10 and 2 hours prior to FDC
of GZR/EBR did not have a clinically relevant effect on SD
GZR AUC0-∞, Cmax, and C24, with geometric mean ratios
(GMRs) [90% confidence intervals (CIs)] of 1.10 [0.95, 1.28,
0.89 [0.71, 1.11], and 1.12 [0.97, 1.30], respectively. FAM
also did not have a clinically relevant effect on EBR AUC0-∞,
Cmax, and C24, with GMRs [90% CIs] of 1.05 [0.92, 1.19],
1.11 [0.98, 1.26], and 1.03 [0.91, 1.17], respectively. Similarly,
coadministration of PAN with GZR/EBR FDC did not
have a clinically relevant effect on SD GZR AUC0-∞, Cmax,
and C24, with GMRs [90% CIs] of 1.12 [0.96, 1.30], 1.10
[0.89, 1.37], and 1.17 [1.02, 1.34], respectively. PAN also
did not have a clinically relevant effect on EBR AUC0-∞, Cmax,
and C24, with GMRs [90% CIs] of 1.05 [0.93, 1.18], 1.02
[0.92, 1.14], and 1.03 [0.92, 1.17], respectively. Conclusions
Coadministration of GZR/EBR FDC with FAM or PAN
had no clinically relevant effect on the PK of GZR or EBR. These
results demonstrate that acid-reducing agents, such as H2-receptor
antagonist and proton-pump inhibitors, may be coadministered
with the GZR/EBR FDC in HCV-infected patients
without restriction.
Disclosures:
Hwa-Ping Feng - Employment: Merck
Pavan Vaddady - Employment: Merck & Co., Inc.
Deborah L. Panebianco - Employment: Merck
Luzelena Caro - Employment: Merck & Co., Inc.
Joan R. Butterton - Employment: Merck Sharp & Dohme Corp.; Stock Shareholder:
Merck Sharp & Dohme Corp.
Marian Iwamoto - Employment: Merck Sharp & Dohme Corp.
Wendy W. Yeh - Employment: Merck
The following authors have nothing to disclose: Patrice Auger, Xiaobi Huang,
Fang Liu, Chun Feng, Nadia Cardillo Marricco, Vanessa Levine, David Goblet,
Michael Gartner, Daria Stypinski
732
Viral suppression with IFN-free therapies ameliorates
portal hypertension in patients with hepatitis C-related
cirrhosis
Mattias Mandorfer, Karin Kozbial, Philipp Schwabl, Clarissa Freissmuth,
Remy Schwarzer, Rafael Stern, Simona Bota, Thomas
Reiberger, Albert Stättermayer, Wolfgang Sieghart, Sandra Beinhardt,
Michael Trauner, Harald Hofer, Arnulf Ferlitsch, Peter Ferenci,
Markus Peck-Radosavljevic; Department of Internal Medicine
III, Medical University of Vienna, Vienna, Austria
Background: Interferon (IFN)-free regimens are highly effective
and generally well tolerated. Portal pressure, assessed by
hepatic venous pressure gradient (HVPG) measurement, drives
the development of liver-related events and mortality. Since a
decrease in HVPG translates into an immediate clinical benefit,
it is an excellent surrogate endpoint. Aim: To investigate the
effect of IFN-free treatments on portal pressure in patients with
hepatitis C-related cirrhosis. Methods: Our study comprises 25
patients with hepatitis C-related cirrhosis and portal hypertension
(HVPG ≥6mmHg) at baseline (BL) who underwent HVPG
measurement after 12-24 weeks of sofosbuvir-based IFN-free
therapy (FU). Concomitant medication known to have an effect
on HVPG, including but not limited to beta blockers, were
paused prior to the HVPG measurements. Results are reported
as median[interquartile range] or mean±standard deviation.
Results: The majority of patients had Child-Pugh stage (CPS)
A (80%[20/25]) and compensated cirrhosis (92%[23/25]).
Ascites was the reason for decompensation in both patients
and none of the patients had CPS C cirrhosis. Forty-eight percent
(12/25) of patients had varices (small: 67%[8/12]/large:
33%[4/12]) and two patients (8%[2/25]) had a history of variceal
bleeding. All patients had undetectable HCV-RNA at the
time of FU HVPG measurement. Antiviral therapy significantly
decreased HVPG (BL: 16[10.5] vs. FU: 13[11.5]mmHg; mean
of differences: -2.4±3.15mmHg; P20% or
to ≤12mmHg) was observed in 40%(6/15). Sixty-one percent
(11/18) of patients achieved a clinically meaningful HVPG
decrease defined as (A) in patients with CSPH but without varices,
or (B) in patients with a HVPG >12mmHg and varices.
Conclusions: While Afdhal and co-workers did not observe an
effect of viral suppression on HVPG in their study population
comprised of a higher proportion of decompensated CPS B/C
patients, effective antiviral therapy led to an immediate and
clinically meaningful decrease in HVPG in our study. Thus,
IFN-free therapies are likely to become a cornerstone in the
treatment of portal hypertension, especially in patients with
compensated cirrhosis. The results will be updated to include
additional patients and information on potential predictors of
HVPG-response.
Disclosures:
Mattias Mandorfer - Consulting: Janssen; Speaking and Teaching: AbbVie, Gilead,
Janssen, Boehringer Ingelheim, Bristol-Myers Squibb, Roche
Simona Bota - Speaking and Teaching: Janssen Pharmaceutica, Bristol-Myers
Squibb
Thomas Reiberger - Consulting: Xtuit; Grant/Research Support: Roche, Gilead,
MSD, Phenex; Speaking and Teaching: Roche, Gilead, MSD
Wolfgang Sieghart - Grant/Research Support: Bayer Schering Pharma, Bayer
Schering Pharma, Bayer Schering Pharma, Bayer Schering Pharma; Speaking
and Teaching: Bayer Schering Pharma, Bayer Schering Pharma, Bayer Schering
Pharma, Bayer Schering Pharma
Michael Trauner - Advisory Committees or Review Panels: MSD, Janssen, Gilead,
Abbvie; Consulting: Phenex; Grant/Research Support: Intercept, Falk Pharma,
Albireo; Patent Held/Filed: Med Uni Graz (norUDCA); Speaking and Teaching:
Falk Foundation, Roche, Gilead
Harald Hofer - Advisory Committees or Review Panels: Gilead, Abbvie; Speaking
and Teaching: Janssen, BMS, Gilead, Abbvie
Peter Ferenci - Advisory Committees or Review Panels: Idenix, Gilead, MSD,
Janssen, Salix, AbbVie, BMS; Patent Held/Filed: Madaus Rottapharm; Speaking
and Teaching: Gilead, Roche
Markus Peck-Radosavljevic - Advisory Committees or Review Panels: Bayer, Gilead,
Janssen, BMS, AbbVie; Consulting: Bayer, Boehringer-Ingelheim, Jennerex,
Eli Lilly, AbbVie; Grant/Research Support: Bayer, Roche, Gilead, MSD, AbbVie;
Speaking and Teaching: Bayer, Roche, Gilead, MSD, Eli Lilly, AbbVie, Bayer
The following authors have nothing to disclose: Karin Kozbial, Philipp Schwabl,
Clarissa Freissmuth, Remy Schwarzer, Rafael Stern, Albert Stättermayer, Sandra
Beinhardt, Arnulf Ferlitsch