studies

730A AASLD ABSTRACTS HEPATOLOGY, October, 2015
prospective German hepatitis C registry. Results Overall, 836
patients on SOF-containing regimens have been enrolled so
far, 629 (75%) are HCV-monoinfected and 207 (25%) HIV-
HCV co-infected. Of those, 155 (19%) patients were infected
with HCV genotype 3, 120/155 (77%) were male. The median
age (IQR) was 50 years (41 to 55). 65 patients (41%) have
been unsuccesfully treated before, mainly with dual therapy
consisting of pegylated interferon and ribavirin. Liver cirrhosis
was diagnosed in 55 patients (37%), two patients were Child-
Pugh stage B. The sustained virological response (SVR12) rate
in patients treated with SOF/PegIFN/RBV (n=40) was 94%
(2/31). In patients treated with SOF/RBV (n=76), the SVR12
rate was 91% (21/23). In patients treated with SOF/DCV
(n=17) for 12 or 24 weeks or SOF/LDV for 12 or 24 weeks,
only very few patients have reached the SVR12 timepoint but all
responded (4/4). Prior treatment failure did not affect treatment
responses. Patients with liver cirrhosis had a lower response
rate of 86% vs 97% without cirrhosis (p=0.28). Conclusion: In
this large cohort patients with genotype 3 response rates were
promising. Patients with liver cirrhosis responded less well to
the different regimens used. This real-life data underline that
the existing drug combinations are effective tools against HCV
genotype 3.
Disclosures:
Patrick Ingiliz - Consulting: Gilead, Abbvie, Janssen Cilag; Speaking and Teaching:
BMS, MSD, Gilead, Abbvie
Knud Schewe - Advisory Committees or Review Panels: abbvie, gilead, msd,
bms, janssen cilag, viiv, hexal
Thomas Lutz - Advisory Committees or Review Panels: Gilead, MSD, AbbVie,
BMS, Janssen Cilag; Grant/Research Support: Gilead, GlaxoSmithKline, Roche,
MSD, AbbVie, Janssen Cilag; Speaking and Teaching: ViiV, BMS
Christoph Boesecke - Speaking and Teaching: MSD, Boehringer, Gilead, BMS,
Roche, Abbvie, ViiV
Stefan Mauss - Advisory Committees or Review Panels: BMS, AbbVie, Janssen,
ViiV, Gilead; Speaking and Teaching: BMS, AbbVie, Janssen, Gilead, MSD
Heiner W. Busch - Speaking and Teaching: Tibotec, MSD, Janssen, BMS, Gilead
Stefan Christensen - Advisory Committees or Review Panels: BMS, Abbvie, Janssen,
ViiV, Gilead, MSD; Speaking and Teaching: Gilead, MSD, Abbvie, BMS,
ViiV, Reckitt Benckiser, Janssen
Dietrich Hueppe - Advisory Committees or Review Panels: Roche, MSD, Novatis,
Gilead, BMS, Janssen
The following authors have nothing to disclose: Axel Baumgarten, Marcel Schuetze,
Guenther Schmutz, Karl-Georg Simon
1061
A comparison of direct sequencing and PCR- invader
assay for the detection of NS5A Y93H mutation and
response to daclatasvir and asunaprevir therapy in
patients with hepatitis C virus genotype 1b
Kazuhiko Hayashi, Masatoshi Ishigami, Yoji Ishizu, Teiji Kuzuya,
Takashi Honda, Yoshiki Hirooka, Hidemi Goto; Gastroenterology,
Nagoya University, Nagoya, Japan
OBJECTIVES: Interferon free regimen such as daclatasvir (DCV)
and asunaprevir (ASV) was approved for patients with hepatitis
C virus (HCV) genotype 1b. Virologic failure of DCV and
ASV therapy was associated with baseline NS5A polymorphism
such as Y93H mutation and screening for the presence
of Y93H mutation at pretreatment is recommended. The direct
sequencing analysis is standard method to identify Y93H mutation
but needs a lot of efforts and costs. A simple assay based
on the Q-Invader technology was developed to determine and
quantify NS5A Y93H mutant strains with high sensitivity. This
study sought to compare two methods used to detection of
Y93H mutation and evaluate the effect of Y93H mutation on
response to DCV and ASV therapy. METHODS: 121 patients
with HCV genotype 1b were enrolled. All patients were examined
the NS5A Y93H mutation by both direct sequencing
analysis and PCR- invader assay. 45 patients were received
DCV and ASV combination therapy for 24 weeks and were
selected for virologic response study. RESULTS: 112 of 121
(92.7%) patients were able to measure Y93H mutation by
direct sequencing analysis and 109 of 121 (90.1%) patients
were able to measure Y93H mutation by PCR- invader assay.
There are no statistically significant differences of sensitivity
in both methods. 21 of 112 (18.6%) patients were identified
Y93H mutation strain by direct sequencing analysis and 18 of
109 (16.5%) patients were able to detect Y93H mutation by
PCR- invader assay. Twelve patients were defined with Y93H
mutation by both methods and the percent HCV-RNA level of
the Y93H mutant were 10, 24, 53, 55, 85, 89, 89, 95, 98,
99, 99, and 99, respectively. Six patients were detected Y93H
mutation by PCR- invader assay but failed to be detected by
direct sequencing and the percent of the Y93H mutant were 4,
5, 14, 30, 52, and 83, respectively. The difference in detection
rate of Y93H mutation between two methods indicated that
direct sequencing analysis could not measure less than 20%
of minor strains. Nine cases were detected Y93H mutation by
direct sequencing but failed to be detected by PCR- invader
assay. One was Y93C, 3 were Y93H, and 5 were mixed type.
The patients without Y93H mutation by both methods were
achieved to SVR except for one case (97.1%). The other virologic
failure were occurred in patients with Y93H mutation by
either method. CONCLUSIONS: The sensitivity of PCR- invader
assay was as same as that of direct sequencing analysis, but
PCR- invader assay could measure minor strains not possible by
direct sequencing analysis. A combination of direct sequencing
and PCR- invader assay would improve prediction of the
response to DCV and ASV therapy.
Disclosures:
Hidemi Goto - Grant/Research Support: MSD, Roche, Bayer, Bristol-Myers, Eisai,
Ajinomoto, Otsuka, Astra, Tanabe, Takeda
The following authors have nothing to disclose: Kazuhiko Hayashi, Masatoshi
Ishigami, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Yoshiki Hirooka
1062
Prediction for poor virological response and clinical
utility of resistance-associated variant detection in combination
therapy with direct-acting antivirals for HCV
genotype 1
Norio Akuta, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki,
Yoshiyuki Suzuki, Tetsuya Hosaka, Masahiro Kobayashi, Satoshi
Saitoh, Mariko Kobayashi, Yasuji Arase, Kenji Ikeda, Hiromitsu
Kumada; Hepatology, Toranomon Hospital, Tokyo, Japan
BACKGROUND: All-oral combinations of direct-acting antivirals
improved treatment efficacy for patients with HCV infection,
but prediction of poor virological response and clinical utility
of resistance-associated variant (RAV) detection are not clear.
METHODS: 405 interferon-ineligible/intolerant and 340 nonresponder
patients with chronic HCV genotype 1b infection
introduced daclatasvir 60 mg once daily plus asunaprevir 100
mg twice daily for 24 weeks. 44 patients, who failed to triple
therapy of peginterferon plus ribavirin with NS3/4A protease
inhibitor (27 patients of telaprevir, 15 of simeprevir, and 2 of
simeprevir after telaprevir), were included. Sustained virologic
response 24 weeks after treatment (SVR24) and non-virological
response (patients who do not achieve HCV-RNA negativity
during treatment) were evaluated. Patients with virological failure
were tested for RAVs (NS3 substitutions of Q80, D168,
and NS5A substitutions of L31, Y93) by direct sequencing at
the baseline. NS5A-Y93 mutant at baseline was also measured
by comparative quantitative analysis of the Q-Invader assay.
RESULTS: SVR24 was evaluated in 62 patients, and the rates