with DAA + RBV; 5/21 (19.2%) of those treated only with IFN + RBV Results: A total of 288 patients (mean age ± SD, 58.3 ± 9.16; 63.2%
and in 19/93 (17.4%) of patients treated with IFN + RBV + AAD. RR was male; 84.7% white; 49.3% previous injection drug user) were enrolled.
not associated with genre, age, HCV genotype, IL28B, basal ANA-IIF, All HCV GTs 1–6 were included. Baseline Child-Pugh Scores were 5 in
IFNsd, IFNsd + RBV or DAA. However, RR was associated with drug 249 patients (86.5%) and 6 in 37 (12.8%; ≥6 in 1 patient and data
combinations ( p < 0.001), IFNpeg + RBV ( p < 0.001), RBV ( p < 0.001), missing in 1). The baseline platelet count was <100 × 109/L in 68
weeks of IFNpeg ( p < 0.001) and weeks of RBV ( p < 0.001). (23.6%). Treatment was G/P 300/120 mg orally once daily for 12
Multivariate analysis only selected INpeg + RBV (OR: 0.129; IC: weeks in 225 (78.1%) patients and 16 weeks in 63 (21.9%). Glecaprevir
0.047–0.355; p < 0.001) as independently predicting RR. 4 patients, exposure in cirrhotic subjects was approximately 2.2-fold the
previously treated with IFN + RBV, developed anti-RR mostly 6 exposure in noncirrhotic subjects. Pibrentasvir exposures in cirrho-
months after the end of treatment (EOT) with DAA. 7 patients, 4 tics and noncirrhotics were similar. No increase in alanine amino-
previously treated with IFNpeg + RBV, developed anti-RR during or transferase (ALT) to grade 3 or higher occurred during the treatment
up to 12 months after EOT with DAA + RBV. period. No treatment-emergent, AE-related deaths occurred. Most
AEs were mild; the most common were fatigue or headache (Table).

Table: AEs
Event Cirrhotic Patients, n (%)
N = 288
DAA-related AEs
Any 132 (45.8)
Serious AE 0
AE grade ≥3 0
AE leading to 0
discontinuation of
study drug
AEs in ≥10% of patients
Fatigue 58 (20.1)
Headache 47 (16.3)
Conclusions: Autoantibodies against RR were detected only in
patients treated with or with a background of RBV, mainly in
association with IFNpeg. The association of DAA administration and
Conclusions: G/P was well tolerated by HCV-infected patients with
anti-RR seroconversion seems to be RBV-dependent. Its timing is not
compensated cirrhosis despite the 2-fold increase in glecaprevir
in favour of a direct mechanism to explain this association.
exposure in patients with compensated cirrhotics compared with
THU-263 noncirrhotic patients. No grade ≥3 elevations in ALT and no cases
Pharmacokinetics and safety of glecaprevir/pibrentasvir in adults consistent with drug-induced liver injury occurred. No DAA-related
with chronic genotype 1–6 hepatitis C virus infection and serious AEs or DAA-related AEs leading to discontinuation were
compensated cirrhosis: an integrated analysis reported.
E. Gane1, F. Poordad2, J. Valdes3, C.-W. Lin3, W. Liu3, A. Asatryan3,
S. Wang3, C. Stedman4, S. Greenbloom5, T. Nguyen6, M. Elkhashab7,
High sustained virologic response rates in patients with
M.-A. Wörns8, A. Tran9, J.-P. Mulkay10, Y. Yu3, A. Porcalla3, F. Mensa3.
1 chronic hepatitis C virus GT1, 2 or 3 infection following 16
Liver Unit, Auckland City Hospital, Auckland, New Zealand; 2The Texas
weeks of MK-3682/grazoprevir/ruzasvir plus ribavirin after
Liver Institute, University of Texas Health Science Center, San Antonio,
having failed 8 weeks of a triplet drug regimen (Part C of
TX; 3AbbVie, North Chicago, IL, United States; 4Christchurch Hospital and
C-CREST-1 & 2)
University of Otago, Christchurch, New Zealand; 5Toronto Digestive
Disease Associates, Toronto, ONT, Canada; 6Research and Education, Inc, L. Serfaty1, S. Pianko2, Z.B. Ari3, A.L. Laursen4, J. Hansen5, E.J. Gane6,
San Diego, CA, United States; 7Toronto Liver Centre, Toronto, ONT, H.-C. Huang7, S. Jin7, J. Bourque7, H. Liu7, A. Grandhi7, M. Su7,
Canada; 8Universitaetsmedizin der Johannes Gutenberg University, N. Gendrano7, D. Fernsler7, F. Dutko7, B.-Y.T. Nguyen7, J. Wahl7, E. Barr7,
Mainz, Germany; 9University Hospital of Nice, Digestive Centre, Nice, W. Yeh7, R. Plank7, J.R. Butterton7. 1Saint-Antoine Hospital, Paris,
France; 10Hôpital CHU Saint-Pierre, Brussels, Belgium France; 2Monash Health, Clayton, VIC, Australia; 3Sheba Medical Center,
E-mail: Tel Hashomer, Israel; 4Aarhus University Hospital, Skejby, Aarhus N;
Aalborg University Hospital, Aalborg, Denmark; 6Auckland Clinical
Background and Aims: The direct-acting antiviral (DAA) combin- Studies Limited, Auckland, New Zealand; 7Merck & Co., Inc., Kenilworth,
ation of glecaprevir (GLE, NS3A protease inhibitor identified by NJ, United States
AbbVie and Enanta) and pibrentasvir (PIB, NS5A inhibitor) demon- E-mail:
strated high sustained virologic response (SVR) rates of 96–100% in
phase 2 and 3 studies of adults infected with genotypes (GTs) 1–6, Background and Aims: To evaluate a retreatment regimen for
including patients with cirrhosis. We report integrated safety results patients who had virologic relapse following 8 weeks of a 3-drug
from HCV-infected adults with cirrhosis. direct-acting antiviral (DAA) combination: MK-3682 (an NS5B
Methods: Four multicenter, open-label, phase 2 or 3 studies included polymerase nucleotide inhibitor), grazoprevir (GZR, an NS3/4A
HCV-infected adults with compensated cirrhosis who were treat- protease inhibitor), and either elbasvir (EBR) or ruzasvir (RZR, MK-
ment-naïve or treatment experienced with interferon (IFN) or 8408) which are NS5A inhibitors.
pegylated IFN, ribavirin, and/or sofosbuvir. Cirrhosis was confirmed Methods: Genotype (GT)1-, 2-, and 3-infected, non-cirrhotic patients
by liver biopsy, FibroScan score ≥14.6 kPa or FibroTest score ≥0.75 and with chronic HCV infection who relapsed after 8 weeks of therapy
aspartate aminotransferase-to-platelet ratio >2. Excluded were with one of 4 regimens that included a 3-DAA combination of MK-
patients with albumin <2.8 g/dL, international normalized ratio 3682 (300 mg or 450 mg), GZR (100 mg), and either EBR (50 mg) or
>1.5–2.3, or platelets <60,000–90,000/mm3. Pharmacokinetic para- RZR (60 mg) were offered open-label retreatment with 16 weeks of a
meters, adverse events (AEs), and laboratory abnormalities were fixed-dose combination (FDC) of once-daily MK3 [MK-3682
assessed. (450 mg)/GZR (100 mg)/RZR (60 mg)] + ribavirin (RBV). Next-gener-
ation sequencing with a 15% threshold was used to test for resistance-
associated substitutions (RASs).

S306 Journal of Hepatology 2017 vol. 66 | S95–S332