studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 787A
1168
Resistance Analyses of Phase 3 Studies in Korean and
Taiwanese Patients with Chronic Hepatitis C Receiving
Sofosbuvir or Ledipasvir/Sofosbuvir Containing Regimens
Kwang-Hyub Han 2 , Brian Doehle 1 , Hadas Dvory-Sobol 1 , Evguenia
S. Svarovskaia 1 , Ramakrishna K. Chodavarapu 1 , Jenny C. Yang 1 ,
Steven J. Knox 1 , Michael D. Miller 1 , Hongmei Mo 1 , Wan-Long
Chuang 3 ; 1 Gilead Sciences, Foster City, CA; 2 Severance Hospital,
Yonsei University Health System, Korea (the Republic of); 3 Kaohsiung
Medical University Hospital, Kaohsiung City, Taiwan
Background: The prevalence of chronic HCV infection varies
globally, with approximately 1% and 4% of the population
infected in Korea and Taiwan, respectively. Sofosbuvir (SOF)
containing regimens can provide safe and highly effective all
oral treatment regimens for patients infected with genotype
(GT) 1 or 2 HCV. In this study we evaluated the impact of preexisting
resistant-associated variants (RAVs) on treatment outcome
and emergence of RAVs at relapse in patients retreated
with SOF+RBV or ledipasvir (LDV)/SOF for 12 weeks in
Korea and Taiwan. Methods: LDV/SOF (n=178) or SOF+RBV
(n=216) was administered for 12 weeks to Korean or Taiwanese
patients chronically infected with GT1 or 2 HCV. NS5A
and/or NS5B deep sequencing analysis (cut-off of 1%) was
performed for patients at baseline according to the assigned
treatment regimen and at the time of virologic failure in patients
failing to achieve SVR12. Data were compared to reference
sequences and patient baseline sequence for patients failing
to achieve SVR. Results: Virologic failure rates were low
in Korean and Taiwanese patients; 1.1% (2/178) in LDV/
SOF (GT1) recipients and 0.9% (2/216) in those receiving
SOF+RBV (GT2). HCV GT1: Of the 178 patients with GT1
HCV infection, 5 patients were incorrectly genotyped by LiPA
and corrected to GT6 by sequence analysis; all 5 achieved
SVR. Thirty-eight of 172 patients (22%) with available NS5A
sequence data were observed to have baseline NS5A RAVs
with 37/38 (97%) achieving SVR. The Y93H (n=30) and
L31F/I/M/V (n=8) NS5A RAVs as single variants were the
most commonly observed in both populations. Four of the 170
patients with available sequence data (2%) were observed to
have the NS5B RAV L159F at baseline and all achieved SVR.
In the two GT1 patients that relapsed post treatment, one was
observed to have NS5A RAVs at baseline and relapse, and the
other had treatment emergent NS5A RAVs. No NS5B RAVs
were observed in these two patients. HCV GT2: Six of 184
patients (3%) with available baseline NS5B sequencing data
were observed to have M289I/L variants, and all achieved
SVR when treated with SOF+RBV. No other baseline NS5B
RAVs were observed. Two GT2 patients experienced virologic
failure, and no baseline or treatment emergent NS5B RAVs
were observed. Conclusions: Low rates of virologic failure were
observed in Korean and Taiwanese patients and the presence
of NS5A and NS5B RAVs did not affect the treatment outcome
to LDV/SOF and SOF+RBV in patients with GT1 and GT2
infection, respectively. No S282T or other SOF treatment-associated
variants have been detected in the patients that experienced
virologic failure during treatment.
Disclosures:
Brian Doehle - Employment: Gilead Sciences
Hadas Dvory-Sobol - Employment: Gilead Sciences; Stock Shareholder: Gilead
Sciences
Evguenia S. Svarovskaia - Employment: Gilead Sciences Inc.; Stock Shareholder:
Gilead Sciences Inc.
Ramakrishna K. Chodavarapu - Employment: Gilead Sciences, Inc
Jenny C. Yang - Employment: Gilead Sciences, Inc
Steven J. Knox - Employment: Gilead Sciences
Michael D. Miller - Employment: Gilead Sciences, Inc.; Stock Shareholder: Gilead
Sciences, Inc.
Hongmei Mo - Employment: Gilead Science Inc
Wan-Long Chuang - Advisory Committees or Review Panels: Gilead, Abbvie;
Speaking and Teaching: BMS, Roche, MSD
The following authors have nothing to disclose: Kwang-Hyub Han
1169
Sustained Virologic Response (SVR) of Liver Transplant
Recipients (OLT) with Advanced Hepatitis C Recurrence
(HCVR), All Genotype 1, after Combination Antiviral
Therapy (Rx) with either Telaprevir(TVR) or Sofosbuvir/
Simeprevir (SOF/SIM): A Single Center Experience
Carlos Fasola, Parvez S. Mantry, Jeffrey S. Weinstein, Hector E.
Nazario, Adil Habib, Maisha Barnes, Alejandro Mejia, Edward
A. Dominguez, Richard Dickerman, Stephen Cheng; Liver Institute,
Methodist Dallas Medical Center, Dallas, TX
Aim: Liver allografts of viremic HCV-OLT have a higher risk of
failure. Timely intervention is necessary. However, long-term
outcome reports, especially using newer Rx, is lacking. Methods:
in a 4-year period, we compared 2 groups of OLT-HCVR
Rx: A) TVR (n=19) + Pegylated interferons (P-IFN) + Ribavirin
(RBV) for 12 weeks, followed by P-IFN+RBV for 12-36 weeks
or, B) SOF/SIM (n=28) Rx for 12-24 weeks. Rx criteria: OLT
graft dysfunction and/or HCVR histology (stage 0-4, Batts&Ludwig).
Immunosuppression based on tacrolimus or cyclosporine
+ mycophenolic acid + low-dose prednisone (limited time).
Demographics, laboratory tests, including HCV-RNA levels,
graft and OLT survivals were analyzed. Minimal follow: 24
weeks post end of Rx. Attention focused on rapid virologic
response (RVR: aviremic in < 4 weeks), early virologic response
(EVR: aviremic in < 8 weeks) and SVR (aviremic for > 24 weeks
post Rx). Statistics: t-tests, Chi2-tests and Kaplan-Meier. Results:
The majority of the patients (14/19 and 21/28, 74-75%) were
non-responder or intolerant to previous Rx. Only a quarter of
patients were naive to HCV Rx on each group. No demographic
or laboratory differences were found, except for a
similar incidence of anemia that required epoetin Rx. Liver tests
remained normal in 26/28 (93%) of the SOF/SIM group. The
pre-Rx advanced stage was significantly higher in the SOF/
SIM group (table). No differences were observed regarding
patient and allograft survivals. Three patients (16%) died due
to allograft failure in group A. In group B, 2 (7%) died, one
of them of trauma with stable LFT’s. Three patient relapsed in
the TVR group. No differences, between groups, were found
in the rate of HCV-RNA levels decrease log during the first 8
weeks, however there was a significant difference in the SVR
rates favoring the SOF/SIM combination (table). Conclusions:
Newer anti-HCV therapies have significantly improved the SVR
and outcome of OLT recipients with HCVR. The benefit of SOF/
SIM combination therapy has shown, in our experience, to be
an important addition to the effort of rescueing liver allograft
function post OLT in HCVR recipients.
Characteristics and Outcome of Liver Transplant Recipients with
Hepatitis C Recurrence after Antiviral Therapy
P value < 0.05: 1 vs. 1 and 2 vs. 2