studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 781A
sion] The combination therapy of DCV and ASV for patients
with HCV genotype 1 had highly effectiveness. The efficacy
and the safety of this therapy for old patients were equal to the
therapy for young patients. NS5B polymerase inhibitor sofosbuvir
is not available for patients with severe renal dysfunction.
We may positively select the combination therapy DCV and
ASV for elderly patients, because elderly patients tended to
have decreased renal function.
Disclosures:
The following authors have nothing to disclose: Kenta Motomura, Masayoshi
Yada, Taiji Mutsuki, Masayuki Miyazaki, Takeshi Senju, Motoyuki Kohjima,
Makoto Nakamuta, Akihide Masumoto
1158
Sofosbuvir-based antiviral therapy in HCV patients with
severe renal failure
Jérôme Dumortier 1 , François Bailly 2 , Georges-Philippe Pageaux 3 ,
Anaïs Vallet-Pichard 4 , Sylvie Radenne 2 , François Habersetzer 5 ,
Marie-Claude Gagnieu 1 , Jean Didier Grange 6 , Anne Minello 7 ,
Nassim Kamar 8 , Laurent Alric 9 , Vincent Leroy 10 ; 1 Hôpital Edouard
Herriot, Lyon, France; 2 Croix-Rousse Hospital, Lyon, France; 3 Saint
Eloi University Hospital, Montpellier, France; 4 Cochin Hospital,
Paris, France; 5 University Hospital of Strasbourg, Strasbourg,
France; 6 Tenon Hospital, Paris, France; 7 Dijon University Hospital,
Dijon, France; 8 Rangueil University Hospital, Toulouse, France;
9 Purpan University Hospital, Toulouse, France; 10 CHU A Michallon,
Grenoble, France
Background: Chronic hepatitis C virus (HCV) infection is the
most common chronic liver disease in patients with end stage
renal disease (ESRD). During the last year, second generation
direct acting antivirals have been a revolution for the treatment
of hepatitis C, and sofosbuvir (SOF) is the cornerstone
of modern treatment. Since SOF is eliminated through kidney,
the aim of this multicentre retrospective study was to assess its
antiviral efficacy and tolerability in HCV infected patients with
severe renal failure (including haemodialysed). Patients: Fifty
patients (36 male, mean age 60.5±7.5 years) with chronic
HCV-infection (7 GT1a, 21 GT1b; 6 GT2; 5 GT3; 9 GT4; 2
GT5; cirrhosis: 27/54%) with severe renal failure, i.e. GFR
< 35 mL/min, including 35 haemodialysed, were included
in this study. There were 17 patients with history of kidney
transplantation, 11 patients with history of liver transplantation,
and 27 patients were on waiting list for kidney transplantation.
Fourteen patients were naïve of antiviral treatment. Antiviral
treatment consisted in SOF/ribavirin (RBV) (n=7), SOF/RBV/
PEG-IFN (n=2), SOF/daclatasvir (DCV) ±RBV (n= 30), or SOF/
simeprevir (SMV) ±RBV (n= 11). Treatment duration was 12 or
24 weeks according to regimen. Reduced dose of SOF (400
mg 3 times a week or 400 mg every other day) was given
in all haemodialysed patients. Results. On-treatment response
(rate of undetectable RNA) was as follows: week 4 : 36/44
(82%), week 8 : 38/40 (95%), week 12: 50/50 (100%),
week 24 : 10/10 (100%). Sustained virological response rate
was 27/29 (93%) at 4 weeks (SVR4) and 24/26 (92%) at 12
weeks (SVR12). The 2 patients with virological relapse were
both G3, with severe fibrosis, who were treated for 12 weeks
without RBV. Dose of RBV (n=13) ranged from 200 mg 3 times
a week to 600 mg/day. The mean baseline hemoglobin level
was 11.6±1.4 g/dL and 19 patients were on Epoetin before
starting antiviral therapy. At the end of treatment, the mean
hemoglobin level was 11.7±1.8 g/dL and 19 patients were on
Epoetin. Hemoglobin level was not different in patients receiving
RBV. No patient experienced severe anemia (hemoglobin
level < 8 g/dL) during treatment. In non-haemodialysed
patients, GFR was not significantly modified during treatment
(29.6±6.2 mL/min at base line vs. 27.9±6.5 mL/min at the
end of treatment). No patient had treatment discontinuation
and antiviral therapy was well tolerated. Conclusion. Our
results strongly suggest that SOF-based antiviral therapy, with
reduced dose of SOF, is safe and effective for the treatment of
HCV patients with ESRD, including haemodialysed, similarly
to HCV patients without ESRD. Final SVR12 will be presented.
Disclosures:
Jérôme Dumortier - Board Membership: Novartis, Astellas, Roche; Consulting:
Novartis; Grant/Research Support: Novartis, Astellas, Roche, MSD, GSK
François Bailly - Board Membership: ABBVIE, MSD, BMS, GILEAD; Speaking and
Teaching: JANSSEN
Georges-Philippe Pageaux - Advisory Committees or Review Panels: Roche,
Roche, Roche, Roche; Board Membership: Astellas, Astellas, Astellas, Astellas
Anaïs Vallet-Pichard - Independent Contractor: Schering Plough, Gilead, BMS,
Roche
François Habersetzer - Advisory Committees or Review Panels: Cytheris; Board
Membership: Gilead, BMS; Speaking and Teaching: Gilead, Janssen, Roche,
BMS
Laurent Alric - Board Membership: Schering Plough, Schering Plough, Schering
Plough, Schering Plough; Consulting: MSD; Speaking and Teaching: Roches,
BMS, Gilead, Roches, BMS, Gilead, Roches, BMS, Gilead, Roches, BMS, Gilead,
MSD, Abbvie
Vincent Leroy - Board Membership: Abbvie, BMS, Gilead; Consulting: Janssen,
MSD; Speaking and Teaching: Abbvie, BMS, Gilead, Janssen, MSD
The following authors have nothing to disclose: Sylvie Radenne, Marie-Claude
Gagnieu, Jean Didier Grange, Anne Minello, Nassim Kamar
1159
Therapeutic effect of dual oral therapy with Daclatasvir
and Asunaprevir
Motoyuki Kohjima 1,2 , Kenta Motomura 1 , Toshimasa Koyanagi 1 ,
Seiya Tada 1 , Takeaki Satoh 1 , Naoki Yamashita 1 , Masaki Yokota 1 ,
Rie Sugimoto 1 , Syoji Nagase 1 , Syusuke Morizono 1 , Nobito Higuchi
1 , Tsuyoshi Yoshimoto 1 , Shigeki Tashiro 1 , Yuki Tanaka 1 , Kunitaka
Fukuizumi 1 , Kazuhiro Kotoh 1 , Makoto Nakamuta 1 ; 1 Fukuoka
Kanzo Treatment research (FKT) group, Fukuoka, Japan; 2 Gastroenterology,
Clinical Research Center, Kyushu Medical Center,
National Hospital Organization, Fukuoka, Japan
Background: The dual oral therapy with the first-in-class NS5A
replication complex inhibitor Daclatasvir (DCV) and the
potent NS3 protease inhibitor Asunaprevir (ASV) has recently
approved for the treatment of chronic hepatitis C genotype 1
patients. Previous trials for the treatment was shown promising
results for improving SVR to more than 80% in patients with
HCV genotype 1b. We conducted a prospective, multicenter
study to investigate the effectiveness of the dual oral therapy
with DVC and ASV. Methods: The patients with HCV genotype
1b have been treated with DCV and ASV since Sep. 2014
(n=523). The enrolled population was generally older (median
69 years old) that was consistent with HCV epidemiology in
Japan and predominantly female (63%). HCV genotype and
IL-28B polymorphisms were determined by PCR amplification
and sequencing. HCV resistant associated polymorphisms
were analyzed by direct sequence of the HCV NS3 and NS5A
domains. Results: HCV-RNA declined rapidly after the initiation
of the DCV + ASV treatment, and HCV-RNA was lower than
detection sensitivity limit in 69% of the patients after 2 weeks
and 82% of patients achieved RVR. The viral response of HCV
was not affected by age, sex, liver fibrosis, previous treatment
response, or IL-28B SNPs. The positive rate for HCV-RNA at
4 weeks of treatment was significantly higher in patients with
resistance-associated polymorphism in NS3 or NS5A and RVR
rate was significantly higher in patients with add-on lipid modulators,
pitavastain and EPA. Although 19 patients experienced
viral breakthrough, 8 patients had no resistance-associated
polymorphism in NS3 or NS5A among the patients with viral