ORAL PRESENTATIONS

Conclusions: TSU-68 combined with repeated cTACE did not GZR/EBR/RBV, including 43% with cirrhosis and 84% with prior
improve OS. However, favourable TTTF was observed in patients virologic failure. HCV RNA levels <15 IU/mL were achieved in all
with low VEGF-C and those with BCLC-B HCC receiving TSU- patients at the end of treatment despite a high prevalence of NS3
68. Further study is needed to confirm the potential of VEGF-C RAVs at baseline. Study medications were well tolerated in this
as a predictive marker. TSU-68 treatment was tolerable in HCC population. SVR12 rates, full safety data, and expanded resistance
patients receiving repeated TACE with a high safety profile and results will be presented.
long treatment duration of 1 year.
Table: Baseline characteristics of 79 patients treated with ≥1 dose of study
drug.
Age, yrs
Mean (Median) 54.4 (55)
Viral hepatitis C: Therapy Mean BMI, kg/m2 (SD) 28.0 (4.6)
HCV Genotype, n (%)
1a 30 (38.0)
1b 49 (62.0)
Fibrosis Stage, n (%)
O001 F4 (cirrhosis) 34 (43.0)
C-SALVAGE: GRAZOPREVIR (GZR; MK-5172), ELBASVIR (EBR; F3 8 (10.1)
MK-8742) AND RIBAVIRIN (RBV) FOR CHRONIC HCV-GENOTYPE 1 F0–2 37 (46.8)
(GT1) INFECTION AFTER FAILURE OF DIRECT-ACTING Screening HCV RNA
ANTIVIRAL (DAA) THERAPY Mean, log10 IU/mL (SD) 6.1 (0.5)
DAA Experience, n (%)
1 2 3 4 5
X. Forns , S. Gordon , E. Zuckerman , E. Lawitz , M. Buti , J. Calleja Boceprevir 28 (35.4)
Panero6 , H. Hofer7 , C. Gilbert8 , J. Palcza8 , A. Howe8 , M. DiNubile8 , Telaprevir 43 (54.4)
M. Robertson8 , J. Wahl8 , E. Barr8 , J. Sullivan-Bolyai8 . 1 IDIBAPS and Simeprevir 8 (10.1)
CIBEREHD, Barcelona, Spain; 2 Henry Ford Health System, Detroit, Virologic Failure, n (%) 66 (83.5)
United States; 3 Carmel Medical Center, Haifa, Israel; 4 The Texas Liver Nonresponse to P-R + DAA 15 (19.0)
Breakthrough on P-R + DAA 9 (11.4)
Institute, University of Texas Health Science Center, San Antonio,
Breakthrough on P-R tail after DAA 16 (20.2)
United States; 5 Hospital Universitario Valle Hebron and Ciberehd, Relapse after P-R + DAA 26 (32.9)
Barcelona, 6 Hospital University Puerta de Hierro Majadahonda,
Madrid, Spain; 7 Medical University of Vienna, Vienna, Austria;
8
Merck & Co., Inc., Whitehouse Station, United States O002
E-mail: mark_dinubile@merck.com TREATMENT OF DECOMPENSATED HCV CIRRHOSIS IN PATIENTS
Background and Aims: Treatment options are needed for patients WITH DIVERSE GENOTYPES: 12 WEEKS SOFOSBUVIR AND
who do not achieve SVR on regimens containing DAAs. The NS5A INHIBITORS WITH/WITHOUT RIBAVIRIN IS EFFECTIVE
Phase-2 C-SALVAGE study investigated the safety and efficacy of an IN HCV GENOTYPES 1 AND 3
interferon-free combination of GZR [NS3/4A protease inhibitor (PI)] G.R. Foster1 , J. McLauchlan2 , W. Irving3 , M. Cheung4 , B. Hudson5 ,
and EBR [NS5A inhibitor] with RBV for patients with chronic HCV S. Verma6 , K. Agarwal6 , and HCV Research UK EAP Group. 1 The
GT1 infection who had failed licensed DAA-containing therapy. Blizard Institute, Queen Marys University of London, London, 2 Centre
Methods: C-SALVAGE is an international open-label study of GZR for Virus Research, MRC University of Glasgow, Glasgow, 3 Virology,
100 mg QD, EBV 50 mg QD, and weight-based RBV BID for 12 weeks University of Nottingham, Nottingham, 4 Queen Marys University
in patients with chronic HCV GT1 infection who had failed ≥4 weeks of London, London, 5 University of Nottingham, Nottingham, 6 Kings
of peginterferon and RBV combined with boceprevir, telaprevir, College Hospital, London, United Kingdom
simeprevir, or sofosbuvir. Per protocol, ~80% of the enrolled E-mail: g.r.foster@qmul.ac.uk
subjects were to have experienced virologic failure. Exclusion Introduction: All oral antiviral therapy for patients with HCV
criteria included decompensated liver disease, hepatocellular induced decompensated cirrhosis is now possible. The optimal
carcinoma, HIV or HBV co-infection, thrombocytopenia <50×103 /mL, regimen is unclear, particularly for Genotype 3, and debate
or hypoalbuminemia <3.0 g/dL. HCV RNA levels were measured by continues on which patients benefit. The NHS England Early Access
COBAS TaqMan v2.0 assay. Resistance-associated variants (RAVs) Program (EAP) provided 12 weeks of therapy with sofosbuvir, with
were identified at baseline by population sequencing. The primary or without ribavirin and an NS5A inhibitor to a cohort of ~500
efficacy outcome was a HCV RNA level below the limit of patients with decompensated cirrhosis. Here we evaluate viral
quantification (15 IU/mL) 12 weeks after the end of treatment clearance and safety in the initial 465 patients. This is the first
(SVR12 ). analysis of a large cohort of patients with decompensated cirrhosis
Results: 79 patients were treated with ≥1 dose of study drug due to genotype 3 HCV receiving sofosbuvir plus NS5A inhibitors.
(Table): 33 (42%) were women, 2 (3%) were non-white, 34 (43%) Material and Methods: The EAP allowed physicians to treat
had cirrhosis (including 8 diagnosed by biopsy), 30 (38%) had GT1a patients with decompensated cirrhosis with sofosbuvir combined
infection, and 66 (84%) had a history of virologic failure on a prior with either daclatasvir or ledipasvir +/− ribavirin (NS5A inhibitors
DAA-containing regimen [13 (16%) had failed for other reasons]. All kindly provided prior to license by Gilead and BMS). Choice
had received a PI; none had received sofosbuvir. At entry, 30 (41%) of of therapy was at the clinicians’ discretion. Data and samples
the 73 patients with available NS3 sequencing data harbored RAVs. were collected by HCV Research UK and we present data on
78 (99%) patients completed therapy with 1 early discontinuation those patients due to have reached 4 weeks post therapy by
due to an AE. At the end of therapy, RNA levels were <15 IU/mL in all abstract submission; all were enrolled when daclatasvir was freely
79 (100%) patients. 5 serious AEs (bacterial pharyngitis, laryngeal available.
squamous cell carcinoma, asthma, appendicitis, and urinary tract Results: 17 centres enrolled 465 patients between July and October
infection) were reported, all of which were considered unrelated to 2014, 23 were co-infected with HIV. The Table shows the results
study drugs. and indicates response rates of >80% in patients receiving ribavirin
Conclusions: In the ongoing C-SALVAGE trial, 79 HCV GT1-infected in addition to sofosbuvir and an NS5A inhibitor. For Genotype 3
patients who had failed PI-based regimens were treated with HCV with decompensated cirrhosis both daclatasvir and ledipasvir

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were effective with a numerical increase in patients achieving SVR4
with daclatasvir, although this was not statistically significant. 91
patients required reduction in ribavirin dosing.
19 patients (4%) died during the study (11 on therapy), 16 (3.4%)
required transplantation and 181 (39%) had an SAE, which was
related to therapy in 143 patients (31%). In 19 patients (4%)
liver function deteriorated (worsening ascites/encephalopathy/new
variceal bleed) but in 215 patients (46%) ascites/encephalopathy
improved.
Conclusions: In decompensated cirrhosis 12 weeks therapy with
sofosbuvir plus an NS5A inhibitor is effective with most patients
achieving SVR4. Patients infected with Genotype 1 HCV respond
well with >80% achieving SVR4, response rates were slightly
reduced in patients with G3. In this fragile population with end
stage liver disease deaths and progression of liver disease were not
uncommon but nearly half the patients had improvements in liver
function.
Table: SVR4 rates in patients with decompensated cirrhosis receiving
12 weeks therapy with different treatment regimes
SOF/LDV SOF/LDV/Riba SOF/DCV SOF/DCV/Riba
Overall 21/28 (75%) 212/251 (84%) 12/15 (80%) 142/171 (83%)
Genotype 1 17/21 (81%) 144/163 (88%) 4/5 (80%) 40/45 (89%)
Genotype 3 4/7 (57%) 44/61 (72%) 5/7 (71%) 92/113 (81%)
Other genotypes 0 24/27 (89%) 3/3 (100%) 10/13 (77%)
Numbers are SVR4/total available for analysis (%).
O003
CAN HEPATITIS C TREATMENT BE SAFELY DELAYED? EVIDENCE
FROM THE VETERANS ADMINISTRATION HEALTHCARE SYSTEM
J.S. McCombs1 , I. Tonnu-MiHara2 , T. Matsuda1 , J. McGinnis1 , S. Fox3 .
1
Schaeffer Center for Health Policy and Economics, Los Angeles,
2
Veterans Administration Healthcare System, Long Beach, 3 Keck School
of Medicine, University of Southern California, Los Angeles, United
States
E-mail: jmccombs@usc.edu
Background and Aims: The cost of new HCV treatments leads
payers and insurance providers to question if delaying treatment
for low risk patients can be accomplished without adversely
impacting the patient. Retrospective patient data from the Veterans
Administration [VA] were used to estimate the impact on patient
risk of treatment initiation before and after the patient’s FIB4 levels
became elevated.
Methods: VA HCV patients with one or more reported FIB-4 values
were selected. Primary outcome measures were time to death and
time to the first occurrence of a composite of liver-related clinical
events. The impact of time to treatment initiation and time to three
different definitions of an elevated FIB4 level were estimated using
a time-dependent Cox proportional hazards models.
Results: 187,860 patients met study requirements. Initiating
treatment before FIB4 >1.00 reduced morbidity by 41% and death
by 36%. Initiating treatment after FIB4 >1.00 remained effective
but diminished in the morbidity risk reduction achieved [30%].
This is not the case if treatment initiation is delayed until after
FIB4 >3.25. The risk reductions associated with treatment initiation
before FIB4 >3.25 were 34% for the composite event and 45% for
death but if initiated after FIB4 >3.25 were only 11% and 25%,
respectively. These detrimental effects of delaying treatment until
FIB4 >3.25 were due to a reduction in the likelihood that treated
patients would achieve viral load suppression and a reduced impact
of viral load suppression on morbidity.
Conclusions: Delaying treatment until after a patient’s FIB4
level exceeds 3.25 has a clear detrimental effect on treatment
effectiveness
Journal of Hepatology 2015 vol. 62 | S187–S212
ORAL PRESENTATIONS
O004
ON-TREATMENT VIROLOGIC RESPONSE AND TOLERABILITY
OF SIMEPREVIR, DACLATASVIR AND RIBAVIRIN IN PATIENTS
WITH RECURRENT HEPATITIS C VIRUS GENOTYPE 1b INFECTION
AFTER ORTHOTOPIC LIVER TRANSPLANTATION (OLT): INTERIM
DATA FROM THE PHASE II SATURN STUDY
X. Forns1 , M. Berenguer2 , K. Herzer3 , M. Sterneck4 , M.F. Donato5 ,
P. Andreone6 , S. Fagiuoli7 , T. Cieciura8 , M. Durlik8 , J.L. Calleja9 ,
Z. Mariño1 , A. Simion10 , U. Shukla11 , T. Verbinnen10 , O. Lenz10 ,
S. Ouwerkerk-Mahadevan12 , M. Peeters10 , R. Kalmeijer11 ,
J. Witek11 . 1 Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD,
Barcelona, 2 Department of Digestive Diseases, Hepatology and Liver
Transplantation Unit, La Fe University Hospital and CIBEREHD,
Valencia, Spain; 3 Department for Gastroenterology and Hepatology,
University Hospital Essen, Essen, 4 Department of Hepatobiliary and
Transplant Surgery, University Medical Center Hamburg-Eppendorf,
Hamburg, Germany; 5 Division of Digestive Diseases, IRCCS
Maggiore Hospital, Milan, 6 Department of Medical and Surgical
Sciences, University of Bologna, Bologna, 7 Gastroenterology and
Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy;
8
Department of Immunology, Transplant Medicine and Internal
Diseases, Transplantation Institute, Medical University of Warsaw,
Warsaw, Poland; 9 Department of Gastroenterology and Hepatology,
University Hospital Puerta de Hierro Mahadahonda, Madrid, Spain;
10
Janssen Infectious Diseases BVBA, Beerse, Belgium; 11 Janssen
Research & Development LLC, Titusville, NJ, United States; 12 Janssen
Research and Development, Beerse, Belgium
E-mail: XFORNS@clinic.ub.es
Background and Aims: Simeprevir (SMV) and daclatasvir (DCV)
are approved for the treatment of hepatitis C virus (HCV) infection
in the non-transplant setting. SMV is a NS3/4A protease inhibitor
and DCV is a NS5A replication complex inhibitor. The combination
of SMV+DCV±ribavirin (RBV) has been previously evaluated in
treatment-naïve and prior null responder patients (pts; LEAGUE-1).
SATURN is an ongoing open-label Phase II study, investigating
SMV+DCV+RBV in pts with recurrent HCV genotype 1b infection
after orthotopic liver transplantation (OLT). Virologic response
and tolerability results are presented from a pre-planned interim
analysis.
Methods: Post-OLT treatment-naïve or -experienced (prior relapser,
partial or null responder to peginterferon±RBV) adults on
stable immunosuppressive therapy following OLT were included.
Part 1 (P1) included pts with METAVIR score F1–F2 on cyclosporine
(CsA) or tacrolimus (TAC). Part 2 (P2) included F1–F4 pts on TAC. Pts
received SMV (150 mg once daily [QD]), DCV (60 mg QD) and RBV
(1–1.2 g/day) for 24 weeks. At the time of analysis, all P1 pts had
reached end of treatment (EOT) and in P2, Week 4 of treatment (or
early discontinuation). Analyses were based on the intent-to-treat
population.
Results: A total of 21 (P1) and 14 (P2) pts were included
(P1/P2: female, 33%/43%; median age, 63.0 years [y]/59.5 y;
mean time since transplantation, 3.98 y/5.36 y; median baseline
HCV RNA 6.9 log10 /6.9 log10 IU/mL; METAVIR F3/F4, 0%/57%). P1
CsA pts had ~6-fold higher SMV plasma concentrations leading
to SMV dose adjustment and exclusion of CsA pts from P2.
On-treatment virologic response is shown in the Table. In P1,
91% of pts had HCV RNA <25 IU/mL undetectable at EOT. In P2,
93% had HCV RNA <25 IU/mL detectable/undetectable at Week 4.
The most common adverse events (AEs) were anaemia (P1/P2:
62%[CsA: 70%/TAC: 55%]/21%) and asthenia (P1: 38%). Grade 3/4
AEs were reported in 19% (P1) and 36% (P2) of pts. Serious AEs
were reported in 24% and 14% of pts, while 2 P1 and 0 P2 pts
discontinued at least one study drug due to an AE. RBV dose
reductions occurred in 3 P1 and 2 P2 pts. Grade 3/4 haemoglobin
decreases and hyperbilirubinemia were observed in 5% and 33%
of P1 and 7% and 36% of P2 pts.
S191