studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1203A
2038
A randomized trial evaluating the antiviral efficacy of
switching from Lamivudine plus Adefovir to Tenofovir
disoproxil fumarate monotherapy in Lamivudine-resistant
chronic hepatitis B patients with undetectable hepatitis
B virus DNA - The 48 week interim analysis
Heon Ju Lee 2 , Jeong Min Kim 1 , Young Oh Kweon 3 , Soo Young
Park 3 , Jeong Heo 4 , Hyun Young Woo 4 , Jaeseok Hwang 1 , Woo
Jin Chung 1 , Chang Hyeong Lee 5 , Byung Seok Kim 5 , Jeong Ill Suh 6 ,
Won Young Tak 3 , Byoung Kuk Jang 1 ; 1 Internal medicine, Keimyung
University School of Medicine, Daegu, Korea (the Republic of);
2 Internal medicine, Yeungnam University College of Medicine,
Daegu, Korea (the Republic of); 3 Internal medicine, Kyungpook
National University College of Medicine, Daegu, Korea (the
Republic of); 4 Internal medicine, Pusan National University School
of Medicine, Busan, Korea (the Republic of); 5 Internal medicine,
Catholic University of Daegu College of Medicine, Daegu, Korea
(the Republic of); 6 Internal medicine, Dongguk University College
of Medicine, Gyeongju, Korea (the Republic of)
Introduction: Tenofovir disoproxil fumarate (TDF) monotherapy
is an effective treatment for patients who have lamivudine
(LAM)-resistant chronic hepatitis B (CHB). However, the efficacy
of switching to TDF monotherapy for LAM resistant CHB patient
with undetectable HBV DNA while on LAM plus adefovir (ADV)
combination therapy (stable switching) is not well established.
Material and Methods: In this non-inferiority trial, LAM-resistant
CHB patients who had undetectable serum HBV DNA (40 IU/mL at two consecutive timepoints,
or persistent HBV DNA levels of 20-40 IU/mL at three
consecutive timepoints. Results: A total of 169 CHB patients
were enrolled in this study including 74(43.8%) with compensated
cirrhosis. There were no significant differences between
two groups in age, gender, biochemistry findings and duration
of LAM and ADV combination therapy at baseline. Twelve
(20.7%) patients in the LAM/ADV group and 18 (16.2%)
patients in TDF group were HBeAg-positive. Nine patients (4 in
the LAM/ADV group and 5 in the TDF group) discontinued the
study. After a mean follow up period of 48 weeks, there were
no subjects in either group who experienced viral reactivation.
The number of patients with HBeAg loss at week 48 was
2/12(16.7%) and 3/18(16.7%) in the LAM/ADV and TDF
groups, respectively. Two patients achieved HBeAg seroconversion
(1/12 [8.3%] in LAM/ADV group and 1/18 [5.6%]
in TDF group). Transient virological rebound occurred in 10
patients (5 patients in LAM/ADV group and 5 patients in TDF
group) through 48 weeks; however, all patients subsequently
achieved HBV DNA undetectablility at the next study visit. No
patient experienced significant increases in serum creatinine
levels above baseline. The mean changes in serum creatinine
levels of both groups were minimal throughout the 48 weeks of
treatment. Conclusions: Stable switching to TDF monotherapy
for 48 weeks demonstrated a comparable virological response
to maintaining LAM plus ADV combination therapy in LAM-resistant
CHB patients with undetectable HBV DNA. (Trial registration
number Clinicaltrial.gov ID NCT01732367)
Disclosures:
Jeong Heo - Grant/Research Support: Roche
Won Young Tak - Advisory Committees or Review Panels: Gilead Korea; Grant/
Research Support: SAMIL Pharma; Speaking and Teaching: Bayer Korea
The following authors have nothing to disclose: Heon Ju Lee, Jeong Min Kim,
Young Oh Kweon, Soo Young Park, Hyun Young Woo, Jaeseok Hwang, Woo
Jin Chung, Chang Hyeong Lee, Byung Seok Kim, Jeong Ill Suh, Byoung Kuk Jang
2039
WITHDRAWN
2040
Association between Pre-S2 Deletions and Virologic
Rebound during Peginterferon Therapy in Patients with
Hepatitis B E Antigen-Positive Chronic Hepatitis B
Cheng-Yuan Peng 1 , Chao-Jen Shih 2 , Pei-Shuan Lo 1 , Chia-Lin
Huang 1 , Chia-Hsin Lin 1 , Hsueh-Chou Lai 1 , Wen-Pang Su 1 ; 1 Division
of Hepatogastroenterology, Department of Internal Medicine,
China Medical University Hospital, Taichung, Taiwan; 2 Agricultural
Biotechnology Research Center, Academia Sinica, Taipei,
Taiwan
Background: To determine the incidence of on-treatment virologic
rebound (VR) during peginterferon (Peg-IFN) therapy in
patients with HBeAg-positive chronic hepatitis B (CHB) and its
association with genomic mutations in hepatitis B virus (HBV).
Methods: We analyzed the on-treatment HBV DNA kinetics
in 103 consecutive HBeAg-positive CHB patients treated with
Peg-IFN for 24 (n=58) or 48 weeks (n=45). On-treatment
serum HBV DNA levels were measured every 3 months (Cobas
Amplicor HBV Monitor Test, Roche Diagnostics, sensitivity:
60 IU/mL). VR was defined as an on-treatment increase in
HBV DNA level of >1 log IU/mL over prior nadir level with or
without an initial decline. Full-length HBV genomic population
sequencing was done at baseline, nadir, VR, and 24 weeks
off therapy. Precore and basal core promoter mutations and
the pre-S2 deletions were examined at baseline. Proportions
of the pre-S2 deletion mutants among total viral populations
were measured using quantitative PCR at baseline, nadir, VR,
and 24 weeks off therapy. The replication capability of HBV
mutants was determined after transient transfection with the
pTriEx-HBV vector in Huh7 cell line. Results: Twelve (12%)
patients displayed on-treatment VR. Univariate analysis identified
HBV DNA