studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 749A
dL (IQR: 0.5 – 0.9 mg/dL). Of the patients with data available
12-weeks after the end-of-treatment, 43/48 (90%) achieved
SVR12. Of the 5 patients who failed, 4 relapsed within the first
4 weeks after the end-of-treatment. One patient was sent to hospice
after a hospitalization for acute cholangitis with elevated
total bilirubin, rectal bleeding, and worsening renal function.
The average cost of pharmaceuticals per patient was $90,234.
The average cost-per-SVR was $100,727. Compared to treatment
with SMV/SOF, the cost-per-SVR with LDV/SOF was on
average $68,337 lower. Conclusions: We observed high SVR
rates (90%) with LDV/SOF in standard clinical practice. The
cost-per-SVR was $100,000 and was approximately $68,000
less than previous treatments. Future investigations of real-world
SVR rates are needed.
Disclosures:
Kian Bichoupan - Consulting: Janssen, Gilead
Alyson Harty - Advisory Committees or Review Panels: Gilead; Consulting: Gilead,
Jannsen, Acaria Pharmacy, Abbvie
David B. Motamed - Advisory Committees or Review Panels: Gilead Pharmaceuticals
Viktoriya Khaitova - Advisory Committees or Review Panels: Gilead, Johnson
and Johnson
Charissa Y. Chang - Consulting: Gilead, Vertex, Onyx
Jennifer Leong - Advisory Committees or Review Panels: Gilead; Consulting:
Bayer
Scott L. Friedman - Advisory Committees or Review Panels: Pfizer Pharmaceutical;
Consulting: Conatus Pharm, Exalenz, Genfit, Exalenz Biosciences, Eli Lilly PHarmaceuticals,
Fibrogen, Boehringer Ingelheim, Nitto Corp., Immune Therapeutics,
Synageva, Roche/Genentech Pharmaceuticals, DeuteRx, Abbvie, Novartis,
RuiYi, Kinemed, Sanofi Aventis, Takeda Pharmaceuticals, Nimbus Therapeutics,
Bristol Myers Squibb, Astra Zeneca, Sandhill Medical Devices, Galmed, Northern
Biologics, Enanta Pharmaceuticals, Regado Bioscience, Raptor Pharmaceuticals,
Teva Pharmaceuticals, Zafgen Pharmaceuticals, Merck Pharmaceuticals,
Debio Pharmaceuticals; Grant/Research Support: Galectin Therapeutics, Tobira
Pharm; Stock Shareholder: Angion Biomedica, Intercept Pharma
Albert Min - Consulting: Bristol Myers Squibb, Gilead, Janssen, Merck; Grant/
Research Support: Bristol Myers Squibb, Gilead; Speaking and Teaching: Bristol
Myers Squibb, Gilead
Douglas Dieterich - Advisory Committees or Review Panels: Gilead, BMS, Abbvie,
Janssen, Merck, Achillion
Andrea D. Branch - Grant/Research Support: Gilead, Janssen
The following authors have nothing to disclose: Daniel J. Waintraub, Neal M.
Patel, Sweta Chekuri, Joshua Hartman, Alicia Stivala, Angela Woody, Meena
B. Bansal, Priya Grewal, Ritu Agarwal, Gene Y. Im, Lawrence Liu, Joseph A.
Odin, Nancy Bach, Thomas D. Schiano, Ponni V. Perumalswami, Lan S. Wang,
Jahnavi Naik
1096
IFN-λ inhibits miR-122 transcription through a Stat3-
HNF4a inflammatory feedback loop in an IFN-α resistant
HCV cell culture system
Fatma Aboulnasr 1 , Sidhartha Hazari 1 , Partha K. Chandra 1 , Pauline
Ferraris 1 , Rajesh Panigrahi 1 , Srinivas Chava 1 , Ramazan Kurt 1 ,
Kyoungsub Song 1 , Asha Dash 1 , Luis A. Balart 2 , Tong Wu 1 , Srikanta
Dash 1,2 ; 1 Pathology, Tulane University, New Orleans, LA;
2 Medicine, Division of Gasteroenterology and Hepatology, Tulane
University, New Orleans, LA
Background: HCV replication in persistently infected cell culture
remains resistant to IFN-α /RBV combination treatment,
whereas IFN-λ1 induces viral clearance. The antiviral mechanisms
by which IFN-λ1 induces sustained HCV clearance
have not been determined. Aim: To investigate the mechanisms
by which IFN-λ clears HCV replication in an HCV cell
culture model. Methods: IFN-α sensitive (S3-GFP) and resistant
(R4-GFP) cells were treated with equivalent concentrations of
either IFN-λ1 or IFN-α.The relative antiviral effects of IFN-α
and IFN-λ1 were compared by measuring the HCV replication,
quantification of HCV-GFP expression by flow cytometry, and
viral RNA levels by real time RT-PCR. Activation of Jak-Stat
signaling, interferon stimulated gene (ISG) expression, and
miRNA-122 transcription in S3-GFP and R4-GFP cells were
examined. Results: We have shown that IFN-λ1 induces HCV
clearance in IFN-α resistant and sensitive replicon cell lines
in a dose dependent manner through Jak-Stat signaling, and
induces STAT1 and STAT2 activation, ISRE-luciferase promoter
activation and ISG expression. Stat3 activation is also involved
in IFN-λ1 induced antiviral activity in HCV cell culture. IFNλ1
induced Stat3 phosphorylation reduces the expression of
hepatocyte nuclear factor 4 alpha (HNF4α) through miR-24 in
R4-GFP cells. Reduced expression of HNF4α is associated with
decreased expression of miR-122 resulting an anti-HCV effect.
Northern blot analysis confirms that IFN-λ1 reduces miR-122
levels in R4-GFP cells. Our results indicate that IFN-λ1 activates
the Stat3-HNF4a feedback inflammatory loop to inhibit miR-
122 transcription in HCV cell culture.
Disclosures:
Luis A. Balart - Advisory Committees or Review Panels: abbvie, Genentech;
Grant/Research Support: Merck, Genentech, Bayer, conatus, Ocera, Hyperion,
Gilead Sciences, Bristol Myers Squibb, abbvie, Vertex, Merck, Genentech,
Bayer, Conatus, Ocera, Hyperion, Gilead Sciences, Bristol Myers Squibb,
Mochida, Eisai, Vertex, takeda, GI Dynamics, tobira; Speaking and Teaching:
Merck, Merck, Merck, Merck, Abbvie, janssen
The following authors have nothing to disclose: Fatma Aboulnasr, Sidhartha
Hazari, Partha K. Chandra, Pauline Ferraris, Rajesh Panigrahi, Srinivas Chava,
Ramazan Kurt, Kyoungsub Song, Asha Dash, Tong Wu, Srikanta Dash
1097
Efficacy of Daclatasvir/Asunaprevir According to Resistance
Associated Variants in Chronic Hepatitis C Genotype1b
Etsuko Iio 1 , Noritomo Shimada 2 , Hiroshi Abe 3 , Masanori Atsukawa
4 , Kai Yoshiza 5 , Koichi Takaguchi 6 , Yuichiro Eguchi 7 , Hideyuki
Nomura 8 , Tomoyuki Kuramitsu 9 , Jong-Hon Kang 10 , Takeshi
Matsui 10 , Noboru Hirashima 11 , Atsunori Kusakabe 12 , Yasuhito
Tanaka 1 ; 1 Nagoya City University Graduate School of Medical
Sciences, Nagoya, Japan; 2 Ootakanomori Hospital, Kashiwa,
Japan; 3 Jikei University School of Medicine Katsushika Medical
Center, Tokyo, Japan; 4 Nippon Medical School Chiba Hokusoh
Hospital, Chiba, Japan; 5 Machida Municipal Hospital, Tokyo,
Japan; 6 Kagawa Prefectural Central Hospital, Takamatsu, Japan;
7 Saga University Hospital, Saga, Japan; 8 Shin-Kokura Hospital,
Kitakyushu, Japan; 9 Kuramitsu Clinic, Akita, Japan; 10 Teine Keijinkai
Hospital, Sapporo, Japan; 11 National Hospital Organization
Nagoya Medical Center, Nagoya, Japan; 12 Nagoya Red
Cross Hospital, Nagoya, Japan
[Background/Aims] Interferon (IFN)-free daclatasvir (DCV)
and asunaprevir (ASV) therapy for 24 weeks improved efficacy
and safety outcomes for patients with hepatitis C virus
(HCV) infection. The aim of the present study is to assess the
treatment outcome according to resistance associated variants
(RAVs) in NS3/NS5A regions among patients with chronic
HCV genotype 1b infection (HCV-1b). [Methods] 612 patients
with HCV-1b were enrolled at multi centers in Japan. This
study protocol was approved by the appropriate institutional
ethics review committees and written informed consents were
observed. Direct sequencing in NS5A region was performed
for all 612 patients before DCV/ASV therapy. 393 chronic
hepatitis (CH) and 219 liver cirrhosis (LC) patients. The median
age was 71 (30-87) and male was 267 (43.6%). The median
platelet count was 12.6×10 4 /μL and HCV-RNA was 6.1 log
IU/mL. 36 patients had experience of Peg-IFN/RBV/Protease
inhibitors (PI) combination therapy, and 27 with simeprevir
(SMV). [Results] Direct sequencing analysis of 612 patients
administered DCV/ASV therapy showed the existence of 31M
(2.4%), 93H (4.1%), and 31M/93H (0.3%) variants in NS5A
region. The 531 patients received over the 4 weeks of DCV/