studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1311A
sofosbuvir, as shown in the inhibition curves below. A unique
feature of this series is the formation of at least two active
metabolites from each candidate that compete against different
naturally occurring ribonucleoside triphosphates, with IC 50
values
against the NS5B polymerase between 1.7 and 0.11 mM.
AT-337 and AT-339 demonstrated excellent selectivity, with
CC 50
values greater than 100 mM in Huh-7 cells, human bone
marrow stem cells and human cardiomyocytes. Furthermore,
no inhibition of human DNA polymerase α, β or γ, no activity
against other RNA or DNA viruses, and no toxicity in all host
cell lines was observed at concentrations up to 100 mM. Conclusions:
New nucleotide prodrugs potently inhibited the HCV
NS5B polymerase by producing multiple active analogs of different
ribonucleoside triphosphates. IND enabling studies are
underway, targeting clinical evaluation in early 2016.
Disclosures:
Steven S. Good - Employment: Atea Pharmaceuticals Inc.; Stock Shareholder:
Atea Pharmaceuticals Inc.
Jean-Christophe Meillon - Employment: Oxeltis; Independent Contractor: Atea
Pharmaceuticals, Inc.; Stock Shareholder: Oxeltis
The following authors have nothing to disclose: Adel Moussa, Jean-Pierre Sommadossi
2267
The impact of α-fetoprotein level during interferon-free
treatment of hepatitis C virus
Masataka Seike, Koichi Honda, Junya Oribe, Mizuki Endo, Mie
Yoshihara, Masao Iwao, Masanori Tokoro, Kazunari Murakami;
gastroenterology, Oita University, Yufu-city, Japan
AIM: The prevalence of older patients with hepatitis C virus
(HCV) has been increasing in Japan. Elderly patients are at
higher risk for hepatocellular carcinoma (HCC) even after HCV
eradication. The risk of developing HCC is age-dependent, and
patients aged ≥ 75 years occasionally present with HCC. α-Fetoprotein
(AFP) levels after interferon (IFN) therapy for HCV are
significantly associated with hepatocarcinogenesis. However,
the significance of AFP level after IFN-free therapy in older
patients remains unclear. Thus, we analyzed AFP levels during
IFN-free treatment in patients with HCV. Patients and methods:
This study included 63 patients (31 males and 32 females)
with HCV genotype 1b who received 60-mg daclatasvir once
daily plus 100-mg asunaprevir twice daily. The mean age of
these patients was 71.3 years (range, 49–82 years). AFP level
was assessed at baseline and every month. These cases were
followed up by abdominal ultrasonography (US), contrast-enhanced
computed tomography (CT), or ethoxybenzyl contrast
magnetic resonance imaging (MRI) every 3–6 months. Results:
The mean serum AFP level in all patients before treatment was
26.7 ng/ml. AFP level during treatment tended to decrease
immediately and had decreased to 11.7 ng/ml at the end of
treatment. Serum AFP levels in 36 patients decreased to < 5
ng/ml at the end of treatment (group A). The group A patients
had no HCC on abdominal US, CT, or MRI. However, serum
AFP levels in 27 patients decreased to > 5 ng/ml at the end of
treatment or increased during therapy (group B). Twelve group
B patients (44%) were diagnosed with HCC after treatment.
Conclusion: The AFP trend during treatment was useful for predicting
future HCC risk after all-oral therapy with daclatasvir
plus asunaprevir for HCV. Patients with HCV and an AFP level
> 5 ng/ml at the end of treatment should be examined for HCC
by US, CT, and/or MRI as soon as possible.
Disclosures:
The following authors have nothing to disclose: Masataka Seike, Koichi Honda,
Junya Oribe, Mizuki Endo, Mie Yoshihara, Masao Iwao, Masanori Tokoro,
Kazunari Murakami