studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 759A
1115
Resistance-associated variants in NS5A region of hepatitis
C virus are susceptible to interferon-based therapy
Jun Itakura, Masayuki Kurosaki, Natsuko Nakakuki, Hitomi
Takada, Nobuharu Tamaki, Yutaka Yasui, Shoko Suzuki, Kaoru
Tsuchiya, Hiroyuki Nakanishi, Namiki Izumi; Division of Gastroenterology
and Hepatology, Musashino Red Cross Hospital, Tokyo,
Japan
BACKGROUND & AIMS: Treatments with direct acting antivirals
(DAAs) has become the standard of chronic hepatitis C treatment
in Japan. But the presence of resistance-associated variants
(RAVs) of hepatitis C virus (HCV) attenuates the efficacy of
DAAs. The aim of this study was to characterize the susceptibility
of RAVs to interferon-based therapy. METHODS: Twenty nine
genotype 1b patients with detectable Y93H variant in NS5A
region at baseline were enrolled and treated by a combination
of simeprevir (NS3/4A inhibitor), pegylated interferon and
ribavirin. The longitudinal changes of RAV were determined
by direct sequencing during therapy and at breakthrough or
relapse, and the longitudinal changes in the proportion of
Y93H RAV were determined by deep sequencing. RESULTS:
By direct sequencing, Y93H RAV became undetectable or its
proportion decreased in 57% of patients with both Y93H and
Y93wild type at baseline at an early time point during therapy
when HCV RNA was still detectable. By deep sequencing, the
proportion of Y93H RAV was decreased from 52.7% (5.8% –
97.4%) at baseline to 29.7% (0.16% - 98.3%) within 7 days of
initiation of treatment (p=0.023). The proportion of Y93H RAV
against Y93 wild type was reduced in 21 of 29 cases (72.4%)
and a marked reduction of more than 10% was observed in
14 cases (48.7%). In 4 cases with breakthrough/relapse, the
proportion of Y93H RAV decreased during therapy and at
breakthrough/relapse but recovered to baseline 3 months after
discontinuation of treatment. HCV RNA reduction was significantly
greater for Y93H RAV (-3.65±1.3 logIU/mL/day) than
the Y93wild type (-3.35±1.0 logIU/mL/day) (p
Shuhei Hige, Itaru Ozeki, Masakatsu Yamaguchi, Mutuumi
Kimura, Tomohiro Arakawa, Tomoaki Nakajima, Yasuaki Kuwata,
Takahiro Sato, Takumi Ohmura, Joji Toyota, Yoshiyasu Karino;
Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan
Background/Aims: One of the most serious problems in the
treatment of hepatitis C is the aging of hepatitis C patients
who had been left behind without being treated with interferon-based
therapy. Combination therapy with daclatasvir (DCV)
and asunaprevir (ASV) is the only option for Japanese patients
with genotype 1b chronic hepatitis C at the moment. However,
the efficacy and safety of DCV/ASV combination therapy has
not been fully elucidated especially for those who are in their
late 70’s and 80’s. The aim of this study was to evaluate the
efficacy and safety of DCV/ASV for senior patients including
pharmacological analysis. Patients and Methods: Two
hundred and ninety-three genotype 1 patients were treated
with fixed daily dose of DCV (60mg) and ASV (200mg) for
24 weeks. The patients were divided into 3 groups by age:
Group I (