studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 709A
gene. Cellular and viral protein expression was evaluated by
western blot using antibodies vs. HCV-NS5A, SOD1, SOD2,
catalase, thioredoxin-1, MAT1, MAT2, PKR, STAT1 and actin.
Results: SAM treatment decreased HCV-RNA levels 50-70%
compared to untreated control (24-72h). Total glutathione levels
increased in both cell lines about 50-60% compared to
control without SAM (6h post-treatment in replicon cells and 2h
post-treatment in parental cells). Transcriptional expression of
SOD1, SOD2 and thioredoxin-1 was increased (0.5, 2.5 and
2 fold-times respectively compared to control) at different time
points (24-72h). This effect was not observed for catalase. Interestingly,
there was no significant change in ROS levels in both
cell types upon SAM treatment at all times assessed, contrary
to the observed with PDTC exposition where an average of
30% reduction was detected (0.5-24h). In other hand, MAT1
expression was increased (2.5 fold-times at 48h) and MAT2
was decreased upon SAM exposition (24h) compared with
untreated cells at both transcriptional and translational level
in both cell lines. SAM treatment does not modify STAT1 and
PKR expression compared to untreated cells (24-72h), however
both protein levels were increased upon IFN-a treatment used
as a control. Conclusions: A possible mechanism by which
SAM decreases HCV expression could involve modulating
antioxidant enzymes systems, biosynthesis of glutathione and
switching MAT2/MAT1 turnover in Hepatitis C virus expressing
cells. Proteins PKR and STAT1 were stimulated in the presence
of IFN-a but not with SAM, suggesting that HCV down-regulation
mediated by SAM is independent of IFN-a pathway. This
may have clinical application in terms of understanding the
pathophysiology of the disease. This work was supported by
CONACYT-BASICA CB-2010-01155082.
Disclosures:
The following authors have nothing to disclose: Sonia A. Lozano-Sepulveda, Eduardo
Bautista-Osorio, Paula Cordero, Linda E. Muñoz, Ana Maria G. Rivas-Estilla
1023
Pre-treatment levels of miR-29b are associated with
response to treatment and stage of fibrosis in patients
with chronic hepatitis C [CHC]
Hossein Sendi 1 , Marjan Mehrab-Mohseni 2 , Mark W. Russo 2 ,
Philippe J. Zamor 2 , Paul A. Schmeltzer 2 , Nury Steuerwald 2 , Judith
Parsons 2 , Mark G. Clemens 4 , Keith Kaplan 3 , W. Carl Jacobs 3 ,
William A. Ahrens 3 , Herbert L. Bonkovsky 1 ; 1 Gastroenterology,
Wake Forest Baptist Medical Center, Winston Salem, NC; 2 Liver,
Carolinas Medical Center, Charlotte, NC; 3 Pathology, Carolinas
Medical Center, Charlotte, NC; 4 Biology, UNC Charlotte, Charlotte,
NC
Both responses to treatment and long-term outcomes of hepatitis
C virus (HCV) infection are critically affected by host genetic
factors. We aimed to determine whether pre-treatment levels
of miR122 or miR-29b play any role in response to treatment
or stage of fibrosis in patients with CHC. A total of 25 CHC
patients (HCV genotype 1) were included in this study, among
whom 11 were treated with IFN plus Ribavirin (with or without
Telaprevir) and 14 remained treatment naïve. The patients
were classified according to their virological responses: early
viral response (EVR): patients whose HCV RNA levels at 12
weeks were reduced by 2-log 10
or more compared to baseline.
Non-EVR (n-EVR): patients whose HCV RNA levels were not
reduced or reduced less than 2- log 10
. Using quantitative real
time PCR, we compared pre-treatment levels of hepatic miR-
122, and miR-29b (normalized to SNORD44) in the patients
based on their response to treatment. We found that pre-treatment
levels of miR-122 were slightly lower in patients with EVR
than those with n-EVR (49 vs 59, p>0.05). However, pre-treatment
levels of miR-29b were significantly lower in patients
with EVR than those with n-EVR (0.015 vs 0.130, p