studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 315A
207
Antiviral Therapy for Chronic Hepatitis B (CHB) Reduces
the Incidence of Hepatocellular Carcinoma (HCC)
Regardless of Cirrhosis Status: Analysis with Adjustment
for REACH-B Risk Score
Derek Lin 2 , Hwai-I Yang 3,4 , Nghia H. Nguyen 12,1 , Joseph K.
Hoang 1 , Yoona Kim 1 , Vinh D. Vu 1 , An K. Le 1 , Kevin T. Chaung 1,5 ,
Vincent G. Nguyen 1,5 , Huy N. Trinh 6 , Jiayi Li 7 , Jian Q. Zhang 10 ,
Ann W. Hsing 8,9 , Chien-Jen Chen 3,11 , Mindie H. Nguyen 1 ; 1 Division
of Gastroenterology and Hepatology, Stanford University
Medical Center, Palo Alto, CA; 2 Department of Medicine, Stanford
University Medical Center, Palo Alto, CA; 3 Genomics Research
Center, Academia Sinica, Taipei, Taiwan; 4 Institute of Clinical
Medicine, National Yang-Ming University, Taipei, Taiwan; 5 Pacific
Health Foundation, San Jose, CA; 6 San Jose Gastroenterology,
San Jose, CA; 7 Palo Alto Medical Foundation, Mountain View,
CA; 8 Cancer Prevention Institute of California, Fremont, CA; 9 Stanford
School of Medicine, Stanford Cancer Institute, Palo Alto, CA;
10 Chinese Hospital, San Francisco, CA; 11 Graduate Institute of Epidemiology
and Preventive Medicine, National Taiwan University,
Taipei, Taiwan; 12 Department of Medicine, University of California
San Diego, San Diego, CA
Objective: Benefits of antiviral therapy on HCC incidence
remains controversial. We aim to examine the effect of antiviral
therapy for CHB on HCC incidence after adjustment for
background risks using a previously validated REACH-B risk
score. Methods: We examined a cohort of 5,908 CHB patients
which included primary analysis of 2,255 from a United
States cohort (973 of these received antiviral therapy) and
3,653 patients from the previously described community-based
Taiwanese REVEAL-HBV study (none received antiviral therapy).
We used Cox proportional hazards models to calculate
the hazard ratios (HRs) of developing HCC with adjustment
using the previously validated REACH-B risk score (17-point
composite score of sex, age, ALT, HBeAg status, and HBV
DNA). Results: There were a total of 273 incident cases: 12
of 973 treated subjects and 263 of 4935 untreated subjects.
There was a significant 77% risk reduction in HCC incidence
in patients with antiviral treatment compared with those without
treatment (HR 0.23; 95% CI 0.13-0.43; pULN). Conclusion: In this large and diverse
cohort of clinic and community participants from two countries,
antiviral therapy was significantly associated with a reduction
in HCC risk after adjustment for background risk using a validated
risk score inclusive of 5 major known predictors of HCC.
To our knowledge, this is the largest assembled CHB cohort to
examine the effect of antiviral therapy.
REACH-B Adjusted HCC Incidence by Treatment
Disclosures:
Yoona Kim - Employment: Proteus Digital Health
Huy N. Trinh - Advisory Committees or Review Panels: BMS, Gilead; Grant/
Research Support: BMS, Gilead; Speaking and Teaching: BMS, Gilead; Stock
Shareholder: Gilead
Mindie H. Nguyen - Advisory Committees or Review Panels: Bristol-Myers
Squibb, Bayer AG, Gilead, Novartis, Onyx; Consulting: Gilead Sciences, Inc.;
Grant/Research Support: Gilead Sciences, Inc., Bristol-Myers Squibb, Novartis
Pharmaceuticals, Roche Pharma AG, Idenix, Hologic, ISIS
The following authors have nothing to disclose: Derek Lin, Hwai-I Yang, Nghia H.
Nguyen, Joseph K. Hoang, Vinh D. Vu, An K. Le, Kevin T. Chaung, Vincent G.
Nguyen, Jiayi Li, Jian Q. Zhang, Ann W. Hsing, Chien-Jen Chen
208
A Single Dose of RG-101, a GalNAc-Conjugated Oligonucleotide
Targeting miR-122, Results in Undetectable
HCV RNA Levels in Chronic Hepatitis C Patients at Week
28 of Follow-up
Meike H. van der Ree 1 , J. Marleen D. Vree 2 , Femke Stelma 1 ,
Sophie Willemse 1 , Marc van der Valk 1 , Svend Rietdijk 3,1 , Richard
Molenkamp 4 , Janke Schinkel 4 , Salah Hadi 5 , Marten Harbers 5 ,
Andre van Vliet 5 , Joanna Udo de Haes 5 , Paul Grint 6 , Steven
Neben 6 , Neil Gibson 6 , Hendrik W. Reesink 1 ; 1 Gastroenterology
and Hepatology, AMC, Amsterdam, Netherlands; 2 Gastroenterology
and Hepatology, UMCG, Groningen, Netherlands; 3 Gastroenterology
and Hepatology, OLVG, Amsterdam, Netherlands;
4 Medical Microbiology, Clinical Virology Laboratory, AMC,
Amsterdam, Netherlands; 5 PRA Healthsciences, Zuidlaren, Netherlands;
6 Regulus Therapeutics, San Diego, USA Minor Outlying
Islands
Background: MicroRNA-122 (miR-122) plays a crucial role in
the hepatitis C virus (HCV) life cycle. Binding of miR-122 to
the 5’UTR of the HCV genome promotes HCV RNA stability
and accumulation, protects the HCV genome from degradation
by cellular exonucleases and prevents induction of an innate
immune response against the virus. The aim of this study was
to evaluate the safety and efficacy of a single dose of RG-101,
a carbohydrate conjugated oligonucleotide that targets miR-
122 in hepatocytes, in chronic HCV patients infected with
various HCV genotypes. Methods: In this multicenter phase
1 study, we included 32 chronic HCV patients with genotype
1, 3 or 4 infection. The first cohort received a single subcutaneous
injection of 2 mg/kg RG-101 (n=14) or placebo (n=2),
the second cohort received a single subcutaneous injection
of 4 mg/kg (n=14) or placebo (n=2). Both cohorts were followed
8 weeks after randomization, and patients with >2 log