studies

254A AASLD ABSTRACTS HEPATOLOGY, October, 2015
patients in care with hepatitis C virus infection (HCV) will
achieve this status in the near future. However, the long term
prognosis in terms of risk or predictors of developing hepatocellular
carcinoma (HCC) among patients with SVR remains
unclear. Methods: A retrospective cohort study using data from
the national VA HCV Clinical Case Registry in patients with
HCV diagnosed (positive HCV RNA) between 10/1999 and
1/2009 who had at-least one year of follow up in the VA.
HCV treatment (pegylated interferon with or without ribavirin)
and SVR status (RNA test negative at least 12 weeks after
the end of treatment) were ascertained. Cox proportional hazards
models were used to examine the effect of demographic,
virological and clinical factors on time to HCC among those
who achieved SVR through end of 2011 while adjusting for
medical comorbidity. We excluded those with HCC diagnostic
codes before SVR date. Results: We had 33,005 HCV-infected
individuals who received HCV treatment during the study timeframe.
Of these, 10,817 patients achieved SVR and 10765
had no HCC before SVR. Their mean age was 53.1 (sd, 6.3),
12.4% were 60 years or older, and 12.9% were Black, 64.4%
non-Hispanic white, and 3.4% Hispanic. Majority (95.3%)
were males; and 53.6% had genotype 1, 25.0% genotype
2, 13.5% genotype 3, 0.7% genotype 4, and 7.2% had no
genotype test available. A total of 124 patients developed
HCC during a total follow of 38,394 person year follow up
(median duration of follow up after SVR was 2.7 years) at
an incidence rate of 0.32% per year. In the cohort with SVR,
patients 60 years and older (HR=6.59 c/w younger age),
Hispanics (HR=2.16, 1.03-4.50 c/w non-Hispanic whites) and
those with cirrhosis (HR=5.58, 3.21 - 9.68) or diabetes (1.82
(0.92 - 3.61) were at an increased risk of developing HCC
compared to their counterparts. Conclusions: The risk of HCC
after HCV cure remains elevated (0.3% per year). Older age
at the time of SVR, Hispanic ethnicity, and presence of cirrhosis
and diabetes are associated with an increased HCC risk
among those who achieve SVR.
Disclosures:
Hashem B. El-Serag - Grant/Research Support: WAKO, Gilead
The following authors have nothing to disclose: Peter Richardson, Fasiha Kanwal
91
Prevalence of Pre-Treatment NS5A Resistance Associated
Variants in Genotype 1 Patients Across Different
Regions Using Deep Sequencing and Effect on Treatment
Outcome with LDV/SOF
Stefan Zeuzem 2 , Masashi Mizokami 3 , Stephen Pianko 4 , Alessandra
Mangia 5 , Kwang-Hyub Han 6 , Ross Martin 1 , Evguenia
S. Svarovskaia 1 , Hadas Dvory-Sobol 1 , Brian Doehle 1 , Phillip S.
Pang 1 , Steven J. Knox 1 , John G. McHutchison 1 , Diana M. Brainard
1 , Michael D. Miller 1 , Hongmei Mo 1 , Wan-Long Chuang 7 ,
Ira M. Jacobson 8 , Gregory Dore 9 , Mark S. Sulkowski 10 ; 1 Gilead
Sciences Inc, Foster City, CA; 2 Department of Internal Medicine,
J.W. Goethe University Hospital, Frankfurt am Main, Germany;
3 National Center for Global Health and Medicine, Tokyo, Japan;
4 Department of Gastroenterology, Monash Medical Centre, Victoria,
VIC, Australia; 5 Liver Unit, IRCCS-Ospedale Casa Sollievo
della Sofferenza, San Giovanni Rotondo, Italy; 6 Department of
Internal Medicine, Yonsei University College of Medicine, Seoul,
Korea (the Republic of); 7 Internal Medicine, Kaohsiung Medical
University Hospital, Kaohsiung, Taiwan; 8 Medicine, Mt. Sinai Beth
Israel, New York, NY; 9 Kirby Institute, UNSW Australia, Sydney,
NSW, Australia; 10 School of Medicine, Johns Hopkins University,
Baltimore, MD
Background: The efficacy of some HCV regimens is influenced
by the presence of certain NS5A resistance associated variants
(RAVs). To investigate if the pretreatment prevalence of
NS5A RAVs in genotypes (GT) 1a and 1b varied by country,
race or ethnicity, comprehensive analyses were performed
using deep sequencing of NS5A from more than 5000 patients
from 17 countries. Methods: NS5A deep sequencing analysis
with a 1% cut-off was performed. GT1a RAVs were defined
as K24G/N/R, M28A/G/T/V, Q30H/G/R/E/K, L31any,
P32L, S38F, H58D, A92K/T, Y93any, and GT1b RAVs were
L31any, P32L, P58D, A92K, Y93any. Results: Pretreatment
samples from 5046 patients were analyzed. Prevalence of
NS5A RAVs was similar between the different regions for both
GT1a and GT1b HCV infected patients (Table). In addition, no
significant differences were observed in NS5A RAV prevalence
between patients with different race or ethnicity. In the subset of
patients who were treated with LDV/SOF for 12 weeks, SVR12
rates were similar in GT1b patients with and without pretreatment
NS5A RAVs across all regions. In GT1a patients with
pretreatment RAVs, SVR12 rates in North America were 91%
(75/82) compared to 98% without NS5A RAVs. All seven
GT1a patients who relapsed had pretreatment NS5A RAVs
conferring >1000-fold reduced susceptibility to LDV (H58D,
Y93H/N/F or multiple RAV combinations). However, 18 GT1a
patients with similar RAVs conferring >1000-fold reduced
susceptibility achieved SVR12 after LDV/SOF for 12 weeks.
Conclusions: No significant difference in prevalence of NS5A
pretreatment RAVs was observed between different regions,
races or ethnicities. Overall, high SVR12 rates (91-100%) were
observed in patients with or without NS5A RAVs with LDV/
SOF. In GT1a patients, lower SVR rate (72%) was observed
in patients with pretreatment NS5A RAVs conferring high level
(>1000-fold) resistance to NS5A inhibitors.
NA: Too few patients treated with LDV/SOF
Disclosures:
Stefan Zeuzem - Consulting: Abbvie, Bristol-Myers Squibb Co., Gilead, Merck
& Co., Janssen
Stephen Pianko - Advisory Committees or Review Panels: Roche, Novartis, GIL-
EAD, Roche, Novartis; Consulting: GILEAD; Speaking and Teaching: JANSSEN
Alessandra Mangia - Advisory Committees or Review Panels: ROCHE, Janssen,
MSD, ROCHE, Janssen, MSD, Boheringer ; Consulting: Gilead; Grant/Research
Support: Shering-Plough, Shering-Plough
Ross Martin - Employment: Gilead Sciences
Evguenia S. Svarovskaia - Employment: Gilead Sciences Inc; Stock Shareholder:
Gilead Sciences Inc
Hadas Dvory-Sobol - Employment: Gilead Sciences; Stock Shareholder: Gilead
Sciences
Brian Doehle - Employment: Gilead Sciences
Phillip S. Pang - Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences
Steven J. Knox - Employment: Gilead Sciences
John G. McHutchison - Employment: Gilead Sciences; Stock Shareholder: Gilead
Sciences
Diana M. Brainard - Employment: Gilead Sciences; Stock Shareholder: Gilead
Sciences
Michael D. Miller - Employment: Gilead Sciences, Inc.; Stock Shareholder: Gilead
Sciences, Inc.
Hongmei Mo - Employment: Gilead Science Inc