studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1197A
using a quantitative ELISA and well-defined monoclonal antibodies
against the S-domain (Total_HBs), the preS1-domain
(LHBs) and the N-glycosylated preS2-domain (MHBs) of the HBs
protein. SHBs levels were derived by subtracting L- and M- HBs
from Total_HBs. Data was log-transformed (log 10
x+1) prior to
analysis. Response was defined as HBeAg seroconversion 24
weeks post-treatment. Results: During treatment, mean HBs fractions
and qHBsAg levels were consistently lower in responders
than non-responders. HBs fractions declined by approximately
1 log by Week 24 (range 0.9-1.2), which was comparable
to the 0.9 log decline observed in qHBsAg levels. Receiver
operating characteristics (ROC) analysis demonstrated that
HBV-DNA, qHBsAg and qHBeAg (but not ALT) levels can predict
treatment response moderately well with area under the
ROC curve (AUROC) scores of 0.70-0.86 (see Table). AUROC
scores for HBs fractions (range 0.70-0.75) were comparable
to qHBsAg scores (0.70-0.74) at each time-point. Conclusions:
The results demonstrate that during PegIFNα-2a therapy, HBs
fractions are lower in responders than non-responders, which
is consistent with the pattern observed with qHBsAg levels. The
ROC analysis demonstrates that individual HBs fraction levels
are equivalent and not superior to qHBsAg levels, for predicting
treatment response in HBeAg-positive patients.
AUROC Scores at Baseline, Week 12 and 24
2027
Liver Gene Expression Profiles Correlate with Virus
Infection and Response to Interferon Therapy in Chronic
Hepatitis B Patients
Chun-Jen Liu, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao, Hui-
Lin Wu; Graduate Institute of Clinical Medicine, National Taiwan
University College of Medicine, Taipei City, Taiwan
Background: The natural course of chronic hepatitis B (CHB)
infection and treatment response are determined mainly by the
genomic characteristics of the individual. We investigated liver
gene expression profiles to reveal the molecular basis associated
with viral infection and IFN-alpha treatment response
in CHB patients. Methods: Nineteen IFN-alpha responders
and 19 non-responders with CHB were included in this study.
Expression profiles were compared between paired liver
biopsy samples taken before and 6 months after successful
IFN-alpha treatment or between pretreatment biopsy samples
of IFN-alpha responders and non-responders. Results: A
total of 132 differentially up-regulated and 39 differentially
down-regulated genes were identified in the pretreatment livers
of CHB patients. The up-regulated genes were mainly related
to immune response and cell proliferation. IFN-alpha and B cell
signatures were also enriched. Lower intrahepatic HBV pregenomic
RNA levels and a total of 118 differentially up-regulated
and 33 differentially down-regulated genes were identified in
IFN-alpha responders. The up-regulated gene set in responders
significantly overlapped with the up-regulated genes associated
with the pretreatment livers of CHB patients. In contrast,
no clear pattern was found in the down-regulated genes of
both analyses. Results of the bioinformatic analyses were validated
in independent cohorts and relevant animal models.
Conclusions: CHB infection evokes significant gene expression
associated with immune responses. The up-regulated genes are
predictive of responsiveness to IFN-alpha therapy, as are lower
intrahepatic levels of HBV pregenomic RNA and pre-activated
host immune responses. Our findings provide novel insights
into the immune mechanism and manipulation of CHB.
Disclosures:
Pei-Jer Chen - Advisory Committees or Review Panels: BMS, GSK, BMS, GSK,
Medigene; Independent Contractor: J & J; Speaking and Teaching: Roche, Roche
The following authors have nothing to disclose: Chun-Jen Liu, Ding-Shinn Chen,
Jia-Horng Kao, Hui-Lin Wu
*HBV-DNA analyses performed on PEgIFN monotherapy cohort
Disclosures:
Michael P. Manns - Consulting: Roche, BMS, Gilead, Boehringer Ingelheim,
Novartis, Idenix, Achillion, GSK, Merck/MSD, Janssen, Medgenics; Grant/
Research Support: Merck/MSD, Roche, Gilead, Novartis, Boehringer Ingelheim,
BMS; Speaking and Teaching: Merck/MSD, Roche, BMS, Gilead, Janssen, GSK,
Novartis
Heiner Wedemeyer - Advisory Committees or Review Panels: Transgene, MSD,
Roche, Gilead, Abbott, BMS, Falk, Abbvie, Novartis, GSK, Roche Diagnostics;
Grant/Research Support: MSD, Novartis, Gilead, Roche, Abbott, Roche Diagnostics;
Speaking and Teaching: BMS, MSD, Novartis, ITF, Abbvie, Gilead
Lei Yang - Employment: Roche (China) Holding Ltd.
Vedran Pavlovic - Employment: Roche Products Ltd; Stock Shareholder: Roche
Products Ltd
Cynthia Wat - Employment: Roche Products Ltd
Markus Cornberg - Advisory Committees or Review Panels: Merck (MSD Germamny),
Roche, Gilead, Novartis, Abbvie, Janssen Cilag, BMS; Grant/Research
Support: Merck (MSD Germamny), Roche; Speaking and Teaching: Merck (MSD
Germamny), Roche, Gilead, BMS, Novartis, Falk, Abbvie
The following authors have nothing to disclose: Franziska Rinker, Corinna M.
Bremer, Steffen B. Wiegand, Birgit Bremer, Dieter Glebe, Anke R. Kraft
2028
A study to evaluate the dynamics changes of HBsAg
quantity and its relation with HBeAg seroconversion following
48 weeks pegylated-interferon-alpha treatment
in patients with HBeAg positive chronic hepatitis B after
long term nucleos(t)ide analogue maintenance therapy
(Roll Over trial) : Interim analysis at 24 weeks
Jeong Heo 1 , Hyun Young Woo 1 , Won Young Tak 2 , Soo Young
Park 2 , Won Lim 1 , Youngmi Hong 1 , Young Oh Kweon 2 , Ki Tae
Yoon 1 , Mong Cho 1 ; 1 Pusan National University Hospital, Pusan,
Korea (the Republic of); 2 Kyungpook National University School of
Medicine, Daegu, Korea (the Republic of)
Background & Aims: Durable post-treatment response is uncommon
in patients with chronic hepatitis B (CHB) on nucleos(t)
ide analogue (NA) therapy. The aim of this study is to investigate
pegylated interferon (PI) after long term NA therapy might
potentiate the antiviral efficacy directly via its effect on broad
antiviral activities and indirectly via activation of innate and
adaptive immune responses leading to HBeAg seroconversion
and eventually HBsAg loss and/or seroconversion. Methods:
The patient with HBeAg-positive CHB who had been treated
with any NA except telbivudine, who have an undetectable
HBV DNA (