ORAL PRESENTATIONS

of disease. Thus, for example, in the Japanese patients 59% were

within Milan Criteria and 71% were suitable for potentially curative

treatment. The comparative figures for Spain were 26&32%, UK

37&38% and Hong Kong, 8&16%, respectively.

Figure: Kaplan–Meier survival curves from the four regions.

Conclusions: In Japan, approximately 80% of the HCC cases are

detected by screening. The comparable figures for the UK, Spain and

Hong Kong data were 15, 35 and <10%. Our data suggest that the

variation in survival is largely accounted for by stage at diagnosis

which is in turn relates to the intensity of screening programs and

the consequent variation in curative therapeutic options.

O111

SAFETY AND EFFICACY OF TREATMENT WITH THE

INTERFERON-FREE, RIBAVIRIN-FREE COMBINATION OF

SOFOSBUVIR + GS-5816 FOR 12 WEEKS IN TREATMENT NAIVE

PATIENTS WITH GENOTYPE 1–6 HCV INFECTION

G.T. Everson1, T.T. Tran2, W.J. Towner3, M.N. Davis4, D. Wyles5,

R. Nahass6, J. McNally7, D.M. Brainard7, L. Han7, B. Doehle7,

E. Mogalian7, W.T. Symonds7, J.G. McHutchison7, T. Morgan8,

R.T. Chung9. 1University of Colorado Denver, Aurora, CO, 2Cedars-Sinai

Medical Center, 3Kaiser Permanente, Los Angeles, CA, 4Digestive

CARE, South Florida Center of Gastroenterology, LLC, Wellington, FL,5University of California, San Diego, CA, 6ID CARE, Hillsborough, NJ,7Gilead Sciences, Inc., Foster City, 8VA Long Beach, Long Beach, CA,9Massachusetts General Hospital, Boston, MA, United States

E-mail: greg.everson@ucdenver.edu

Background and Aims: GS-5816 is a HCV NS5A inhibitor with

potent activity against genotype (GT) 1–6 HCV as demonstrated in

a 3-day monotherapy study. We report the results of a Phase 2

study of sofosbuvir (SOF) + GS-5816 in patients with GT1–6 HCV

infection.

Methods: Treatment naïve GT1–6 HCV-infected patients without

cirrhosis were randomized 1:1 to SOF 400mg + GS-5816 25mg once

daily or SOF 400mg + GS-5816 100mg once daily for 12 weeks.

Results: 154 patients (36% GT1, 14% GT2, 35% GT3, 9% GT4,

<1% GT5, and 6% GT6) were randomized and treated; 64% were

male, 85% white, and 48% had IL28B CC genotype. All but one

patient (GT3, SOF+GS-5816 25mg) had HCVRNA < LLOQ by week

4 of treatment. This patient stopped treatment for non-response

at week 8. HCVRNA results through post-treatment week 4 (SVR4)

are presented below. Across all treatment groups, 96% of patients

achieved SVR4 Two patients relapsed, one with GT1 and one

with GT3; both received SOF+GS-5816 25mg. The most frequently

reported adverse events (>10%) were fatigue, headache and nausea.

There were no discontinuations due to adverse events. Four subjects

reported 5 SAEs; none were considered related to study drug. There

was no evidence of drug related changes in hematologic, chemistry

or urinalysis parameters.

Conclusions: SOF+GS-5816 for 12 weeks was well tolerated and

resulted in high SVR4 rates in patients with genotype 1–6 HCV

infection. The broad coverage of HCV genotypes and the safety

profile of this combination warrants further evaluation.

Table: SVR4 in patients treated with SOF+GS-5816

HCV genotype SOF 400mg + GS-581625mg

SOF 400mg + GS-5816100mg

GT1 96% (26/27) 100% (28/28)GT2 91% (10/11) a 100% (10/10)GT3 89% (24/27) a 100% (27/27)GT4 100% (7/7) 86% (6/7) a

GT5 100% (1/1) −GT6 100% (4/4) 100% (5/5)

a One subject per group was lost to follow-up prior to post-treatmentweek 4.

O112

GENERATION OF MICE WITH SYNGENEIC HUMAN LIVER

AND IMMUNE SYSTEM TO STUDY CELLULAR IMMUNITY TO

HEPATITIS B VIRUS

E. Billerbeck1, M.C. Mommersteeg1, J. Xiao1, M. Dorner1,2, C. Fung1,

L. Andrus1, A. Bhatta1, A. Shlomai1, L. Chiriboga3, C.M. Rice1,

Y.P. de Jong1,4. 1Laboratory of Virology and Infectious Disease, The

Rockefeller University, New York, NY, United States; 2Section of

Virology and Section of Hepatology, Imperial College London, London,

United Kingdom; 3Department of Pathology, New York University

Medical Center, 4Weill Cornell Medical College, New York, NY, United

States

E-mail: ydj2001@med.cornell.edu

Background and Aims: Human liver chimeric mouse models

have proven useful to study many liver conditions afflicting

man, including hepatotropic infections such as hepatitis B virus

(HBV), hepatitis C virus and malaria. In addition, immunodeficient

mice reconstituted with hematopoietic stem cells (HSCs) derived

from fetal human liver reliably develop human hematopoietic cell

subsets. Combining these models has long been hampered by the

inability of human fetal liver progenitor cells (FLPCs) to engraft

and/or proliferate in human liver chimeric animal models.

Methods: We set out to engraft FAH−/− NOD RAG1−/− IL2Rgnull

(FNRG) mice with human FLPCs and, either concurrently or

sequentially, human HSCs with the goal of developing mice doubly

reconstituted with syngeneic human liver and lymphocytes.

Results: We found that supplementing the human cytokine

oncostatin-M, which does not cross-react between mouse and

human, enhanced FLPC engraftment by 5–10 fold. By transplanting

both FLPCs and HSCs we generated mice with moderate levels of

human liver chimerism and good immune reconstitution. Mouse

serum typically contained 10–100mcg/ml of human albumin, and

20–80% of blood mononuclear cells were human. Upon infection

with HBV these mice displayed rapid and sustained viremia. In

addition to hepatic T and B cell repopulation, doubly engrafted

mice showed physiological levels of intrahepatic NK cells, which

were not observed in mice only reconstituted with human HSCs.

Conclusions: These mice offer a significant improvement over

current immunodeficient liver chimeric mouse models and should

facilitate experimental interrogation of immune contributions to

human liver diseases, including further defining the role of cellular

immunity to viruses such as HBV.

S46 Journal of Hepatology 2014 vol. 60 | S45–S66