studies

968A AASLD ABSTRACTS HEPATOLOGY, October, 2015
Disclosures:
Sandi Kwee - Grant/Research Support: Bayer Healthcare
Linda L. Wong - Speaking and Teaching: Bayer, Bayer
Naoky CS C. Tsai - Advisory Committees or Review Panels: Bristol-Myers Squibb,
Gilead, AbbVie; Consulting: BMS, Gilead; Grant/Research Support: BMS,
Gilead, AbbVie; Speaking and Teaching: Bristol-Myers Squibb, Gilead, Salix,
Bayer, AbbVie
The following authors have nothing to disclose: Min-Ae Song, Maarit Tiirikainen,
Gordon S. Okimoto, Brenda Y. Hernandez, Herbert Yu
ng/mL) in this study population, suggesting an opportunity to
improve the current HCC screening for AFP-negative HCC. To
validate the urine DNA test for the early detection of primary
and recurrent HCC, an on-going blinded study was conducted
from a population of HBV-infected cirrhosis patients, with or
without previous HCC. All patients were monitored for severe
liver diseases including HCC. Urine samples were collected
at visits with a hepatologist and were barcoded and tested
for three DNA markers. After a course of 6 to 18 months of
follow-ups, four HCC cases, including three recurrent cases,
were detected by MRI. More significantly, urine DNA markers
detected three of four HCC cases at 6 and 9 months prior to
the time of MRI diagnosis. In conclusion, HCC DNA markers
can be detected in urine of patients with HCC by short-amplicon,
PCR-based assays. Furthermore, we have demonstrated
that in combination with serum AFP, a urine DNA test detected
at least 30% more HCC in an open-labeled study as compared
to serum AFP alone, and therefore, this test has the potential
to detect HCC prior to MRI imaging in a blinded pilot study.
Su, et. al., J Mol Diag, 6, 101-107. (2004) Lin, et al., J Mol
Diag 13: 474-484 (2011) Jain, et al., Hepatology Research,
(2014), doi: 10.1111/hepr.12449
Disclosures:
Hie-Won Hann - Advisory Committees or Review Panels: Gilead; Grant/Research
Support: Gilead, Bristol-Myers Squibb
Surbhi Jain - Employment: JBS Science, Inc
Wei Song - Stock Shareholder: JBS Science Inc
Ying-Hsiu Su - Advisory Committees or Review Panels: JBS Science Inc
The following authors have nothing to disclose: Selena Lin, Sooji Yi, Ting-Tsung
Chang, Chi-Tan Hu
1554
Detection of genetic and epigenetic DNA markers in
urine for the early detection of primary and recurrent
hepatocellular carcinoma
Hie-Won Hann 1 , Surbhi Jain 2 , Selena Lin 6 , Sooji Yi 1 , Ting-Tsung
Chang 3 , Chi-Tan Hu 4 , Wei Song 2 , Ying-Hsiu Su 5 ; 1 Liver Disease
Prevention Center, Division of Gastroenterology and Hepatology,
Thomas Jefferson University Hospital, Philadelphia, PA; 2 JBS Science,
Inc, Doylestown, PA; 3 National Cheng Kung Universtiy Medical
College, Tainan, Taiwan; 4 Buddhist Tzu Chi General Hospital
and Tzu Chi University, Hualien, Taiwan; 5 The Baruch S. Blumberg
Institute, Doylestown, PA; 6 Drexel University College of Medicine,
Philadelphia, PA
The purpose of this study is to explore the potential of urine
DNA biomarkers for the early detection of primary and recurrent
hepatocellular carcinoma (HCC). HCC is an aggressive
disease with a 5-year survival rate of 26%, in early-stage cancers,
and a mere 2% in later stages, with an approximate
50% recurrence rate in the first 2 years of treatment. The most
commonly used screening biomarker is serum alpha-fetoprotein
(AFP), which detects only 40-60% of cases. We have
previously shown that urine contains fragmented, circulation-derived,
cell-free DNA that can be used for detection of
cancer-related DNA markers, if the tumor is present (1). In
order to detect circulation-derived, cell-free DNA markers in
urine, we have developed short amplicon (~50 bp) PCR-based
assays for mutations in TP53 (249T) (2) and for aberrant DNA
methylation in GSTP1 (mGSTP1) and RASSF1A (mRASSF1A
(3)). In addition, we have shown that the AUROC of three urine
DNA markers, mGSTP1, mRASSF1A, and TP53 249T mutations,
in combination with AFP, is 0.98 in detecting primary
HCC (n=74) from non HCC [(cirrhosis (n=45) and hepatitis
(n=42)] patients by a logistic regression-based combination
algorithm. Furthermore, these 3 DNA markers detected 35 of
the 46 (76%) HCC samples that were AFP negative (< 20
1555
Prevalence and serological features of chronic hepatitis
B patients with concurrent HBsAg and anti-HBs in the
Hepatitis B Research Network (HBRN).
William M. Lee 1 , Yona K. Cloonan 2 , Kathleen B. Schwarz 3 , Doan
Y. Dao 1 , Anna S. Lok 4 ; 1 Division of Digestive and Liver Diseases,
University of Texas Southwestern Medical Center at Dallas, Dallas,
TX; 2 Epidemiology, University of Pittsburgh, Pittsburgh, PA; 3 Pediatrics,
Johns Hopkins University School of Medicine, Baltimore, MD;
4 Gastroenterology, University of Michigan, Ann Arbor, MI
Background: Some patients with chronic HBV infection have
concurrent HBsAg and anti-HBs. We examined the HBRN
cohort to determine the prevalence of anti-HBs in participants
with chronic HBV infection, and compared demographic and
clinical factors between participants with and without anti-HBs.
Methods: Data from 1402 (1115 adults and 287 pediatric)
participants with chronic HBV infection enrolled in the HBRN,
who had been tested for both HBsAg and anti-HBs within 1
year of enrollment were included. 139 participants belonging
to specifically targeted groups (e.g., pregnant women) were
excluded from prevalence estimates. Characteristics of anti-HBs
positive and anti-HBs negative participants were compared.
Results: 93 participants were anti-HBs positive, overall prevalence
of concurrent HBsAg and anti-HBs was 6.6% (7.7%
pediatric and 6.3% adult). Age, sex, race and birthplace did
not differ significantly between anti-HBs positive and anti-HBs
negative participants. Similarly, there were no significant differences
in mode of transmission, estimated years of infection,
past HBV treatment, prevalence of HBeAg, HBV genotypes,
AST, ALT or other biochemical markers of liver injury[SB1] in
the 2 groups. HBsAg levels were significantly lower in anti-HBs
positive participants: median 3.0 vs. 3.6 log 10
IU/mL (p