studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 341A
252
Daclatasvir in combination with sofosbuvir with or without
ribavirin is safe and efficacious in liver transplant
recipients with HCV recurrence: Interim results of a multicenter
compassionate use program
Kerstin Herzer 1 , Tania M. Welzel 2 , Peter Ferenci 3 , Joerg Petersen 4 ,
Michael Gschwantler 5 , Markus Cornberg 6 , Thomas Berg 7 , Ulrich
Spengler 8 , Ola Weiland 9 , Marc van der Valk 10 , Hartwig Klinker 11 ,
Jürgen K. Rockstroh 8 , Eckart Schott 12 , Markus Peck-Radosavljevic 3 ,
Yue Zhao 13 , Maria Jesus Jimenez Exposito 14 , Stefan Zeuzem 2 ;
1 Universitätsklinikum Essen (AöR), Essen, Germany; 2 Universitätsklinikum
der Johann Wolfgang Goethe Universität, Frankfurt, Germany;
3 Medizinische Universität Wien, Vienna, Austria; 4 IFI Institut
für Interdisziplinäre Medizin, Hamburg, Germany; 5 Wilhelminenspital,
Vienna, Austria; 6 Medizinische Hochschule Hannover, Hannover,
Germany; 7 Universitätsklinikum Leipzig, Leipzig, Germany;
8 Universitätsklinikum Bonn, Bonn, Germany; 9 Karolinska Institutet,
Solna, Sweden; 10 Academic Medical Center, University of Amsterdam,,
Amsterdam, Netherlands; 11 Universitätsklinikum Würzburg,
Würzburg, Germany; 12 Charité Universitätmedizin Berlin, Berlin,
Germany; 13 Global Biostastistics, Bristol-Myers Squibb, Hopewell,
NJ; 14 Research and Development, Bristol-Myers Squibb, Princeton,
NJ
BACKGROUND: Interferon (IFN)-based therapy for HCV postliver
transplant (LT) has been associated with suboptimal
response and poor tolerability. New IFN-free regimens have
the potential to improve response rates and safety. The all-oral,
pangenotypic regimen of daclatasvir (DCV) and sofosbuvir
(SOF) with ribavirin (RBV) was well tolerated and achieved
high SVR rates in patients with post-LT recurrence or advanced
cirrhosis in the ALLY-1 study. We report here a detailed subanalysis
of LT recipients with HCV recurrence from a compassionate
use program (CUP) of DCV+SOF±RBV. METHODS: This
multicenter CUP, opened in 5 European countries, enrolled
adult patients with chronic HCV infection who are at a high
risk of hepatic decompensation or death within 12 months if
left untreated, and who had no available treatment options.
Patients received DCV 60mg + SOF 400mg once daily for
24 weeks, with RBV added at the physician’s discretion. This
interim analysis includes 87 post-LT patients enrolled in the CUP
with available data on March 16, 2015, of whom 38 patients
have SVR12 data available to date. RESULTS: Most patients
were male (69%), white (93%), with a median age of 58 years
(39–75). Mean (SD) baseline HCV RNA 5.8 (1.7) log 10
IU/
mL. Most patients were infected with HCV GT1 (87%) (1a,
n=28; 1b, n=37; 1 unknown, n=11) or GT3 (8%). Median
time since LT to treatment initiation was 3.3 years. Most frequent
immunosuppressant includes tacrolimus (n=47) and cyclosporine
(n=11). Cirrhosis was present in 35 (40%) patients;
among cirrhotic patients, 13 (37%) were Child-Pugh class B/C,
and 8 (23%) had MELD scores ≥15. Twenty-six (30%) patients
received RBV as part of the regimen. Baseline characteristics
and results for each treatment group are described in the Table.
Overall, of the 38 patients with available HCV RNA values at
posttreatment week 12 to date, all achieved virologic response
(SVR12 100%). Updated SVR12 data will be presented. Serious
AEs occurred in 18 patients (21%), 6 patients discontinued
treatment due to AEs and 3 patients died. CONCLUSION: In
this preliminary analysis of patients in a real-world setting,
DCV+SOF±RBV achieved high rates of SVR12 and was well
tolerated in this difficult-to-treat post-liver transplant patient population.
The use of ribavirin did not affect efficacy outcomes.
Disclosures:
Tania M. Welzel - Advisory Committees or Review Panels: Novartis, Janssen,
Gilead, Abbvie, Boehringer-Ingelheim+, BMS
Peter Ferenci - Advisory Committees or Review Panels: Idenix, Gilead, MSD,
Janssen, Salix, AbbVie, BMS; Patent Held/Filed: Madaus Rottapharm; Speaking
and Teaching: Gilead, Roche
Joerg Petersen - Advisory Committees or Review Panels: Bristol-Myers Squibb,
Gilead, Novartis, Merck, Bristol-Myers Squibb, Gilead, Novartis, Merck; Grant/
Research Support: Roche, GlaxoSmithKline, Roche, GlaxoSmithKline; Speaking
and Teaching: Abbott, Tibotec, Merck, Abbott, Tibotec, Merck
Michael Gschwantler - Advisory Committees or Review Panels: Janssen, BMS,
Gilead, AbbVie; Speaking and Teaching: Janssen, BMS, Gilead, AbbVie
Markus Cornberg - Advisory Committees or Review Panels: Merck (MSD Germamny),
Roche, Gilead, Novartis, Abbvie, Janssen Cilag, BMS; Grant/Research
Support: Merck (MSD Germamny), Roche; Speaking and Teaching: Merck (MSD
Germamny), Roche, Gilead, BMS, Novartis, Falk, Abbvie
Thomas Berg - Advisory Committees or Review Panels: Gilead, BMS, Roche,
Tibotec, Vertex, Jannsen, Novartis, Abbott, Merck, Abbvie; Consulting: Gilead,
BMS, Roche, Tibotec; Vertex, Janssen; Grant/Research Support: Gilead, BMS,
Roche, Tibotec; Vertex, Jannssen, Merck/MSD, Boehringer Ingelheim, Novartis,
Abbvie; Speaking and Teaching: Gilead, BMS, Roche, Tibotec; Vertex, Janssen,
Merck/MSD, Novartis, Merck, Bayer, Abbvie
Ola Weiland - Advisory Committees or Review Panels: Merk, BMS, Medivir, Gilead,
AbbVie; Grant/Research Support; Speaking and Teaching: Merk, Roche,
BMS, Novartis, Janssen, Medivir, Gilead, AbbVie
Marc van der Valk - Advisory Committees or Review Panels: gilead, msd, bms,
abbvie, janssen cilag, viiV, roche
Jürgen K. Rockstroh - Advisory Committees or Review Panels: Abbvie, BI, BMS,
Merck, Roche, Tibotec, Abbvie, Bionor, Tobira, ViiV, Gilead, Janssen; Consulting:
Novartis; Grant/Research Support: Merck; Speaking and Teaching: Abbott,
BI, BMS, Merck, Roche, Tibotec, Gilead, Janssen, ViiV
Eckart Schott - Advisory Committees or Review Panels: Gilead, Roche, Bayer,
BMS, Abbvie; Speaking and Teaching: Gilead, Novartis, Roche, MSD, Bayer,
Falk, BMS, Janssen, Abbvie
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
Maria Jesus Jimenez Exposito - Employment: Bristol-Myers Squibb
Stefan Zeuzem - Consulting: Abbvie, Bristol-Myers Squibb Co., Gilead, Merck
& Co., Janssen
The following authors have nothing to disclose: Kerstin Herzer, Ulrich Spengler,
Hartwig Klinker, Yue Zhao
253
Molecular heterogeneity in multinodular Hepatocellular
Carcinoma
Daniela Sia 1,2 , Andrew Harrington 1 , Zhongyang Zhang 3 , Genis
Camprecios 1 , Sara Toffanin 1 , Agrin Moeini 1,2 , M. Isabel Fiel 1 ,
Ke Hao 3 , Monica Higuera 2 , Oriana Miltiadous 1 , Laia Cabellos 2 ,
Helena Cornella 2 , Yujin Hoshida 1 , Sander S. Florman 1 , Myron E.
Schwartz 1 , Josep M. Llovet 1,2 ; 1 Liver Cancer Program, Dept of Liver
Diseases, Icahn School of Medicine at Mount Sinai, New York,
NY; 2 Liver Cancer Translational Research Laboratory, IDIBAPS,
Hospital Clinic, Barcelona, Spain; 3 Icahn Institute for Multiscale
Biology, Icahn School of Medicine at Mount Sinai, New York, NY
Introduction: Whether multinodular hepatocellular carcinomas
(HCCs) result from intrahepatic metastasis (IM or clonal tumors)