studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 273A
Disclosures:
The following authors have nothing to disclose: Prabhu P. Gounder, Lisa Bulkow,
Mary Snowball, Susan Negus, Philip R. Spradling, Brian J. McMahon
126
Relationship between hepatocellular carcinoma development
and serum viral markers in chronic hepatitis B
patients who achieved undetectable serum HBV DNA
while on long-term nucleoside analogue therapy
Ka-Shing Cheung 1 , Wai-Kay Seto 1 , Danny Wong 2 , Ching-Lung
Lai 1 , Man-Fung Yuen 1 ; 1 Medicine, Queen Mary Hospital, The University
of Hong Kong, Hong Kong, Hong Kong; 2 Queen Mary
Hospital, Hong Kong, Hong Kong
Background: Hepatitis B surface antigen (HBsAg) and hepatitis
B core-related antigen (HBcrAg) are risk factors for the
development of hepatocellular carcinoma (HCC). Linearized
HBsAg (HQ-HBsAg) is a more sensitive assay to measure
HBsAg level. However, their roles in predicting HCC development
are unknown when there is profound viral suppression
by nucleos(t)ide analogues (NA). Methods: Seventy-six chronic
hepatitis B (CHB) patients who developed HCC in 2007-2014
despite undetectable serum HBV DNA level after at least oneyear
NA therapy were recruited. 152 CHB patients without
HCC were recruited as controls. They were matched by age,
gender, HBeAg status, cirrhosis status, undetectable serum HBV
DNA and duration of NA therapy with the 76 HCC patients in
a 2:1 ratio. Serum HBsAg, HQ-HBsAg and HBcrAg levels were
analysed and compared between the two groups. Results: A
statistically significant difference in the HBcrAg level was noted
between the HCC group and non-HCC groups (10.2 and 1.7
kU/mL respectively, p=0.005), but was not observed in HBsAg
or HQ-HBsAg levels. The area under receiver operating characteristic
curve (AUROC) was 0.61 (95% CI: 0.54-0.69) with a
negative predictive value (NPV) of 77.0% when a cutoff value
of HBcrAg level ≥7.8 kU/mL was used. The odds ratio of HCC
development was 3.27 (95% CI: 1.84-5.80). In the subgroup
analysis for non-cirrhotic patients, a statistically significant
difference in the HBcrAg level was noted between the HCC
group and non-HCC groups (10.2 and 1.0 kU/mL respectively,
p=0.001). The AUROC was 0.70 (95% CI: 0.58-0.81) with a
NPV of 80.6% when a cutoff value of HBcrAg level ≥7.9 kU/
mL was used. The odds ratio of HCC development was 5.95
(95% CI: 2.35-15.07). Conclusion: HBcrAg (but not HBsAg or
HQ-HBsAg) can predict HCC risk in CHB patients who achieve
undetectable serum HBV DNA while receiving NA therapy.
Future prospective studies are warranted to further define the
role of HBcrAg level in this group of patients.
Disclosures:
Wai-Kay Seto - Advisory Committees or Review Panels: Gilead Science; Speaking
and Teaching: Bristol-Myers Squibb
Ching-Lung Lai - Advisory Committees or Review Panels: Bristol-Myers Squibb,
Gilead Sciences Inc; Consulting: Bristol-Myers Squibb, Gilead Sciences, Inc;
Speaking and Teaching: Bristol-Myers Squibb, Gilead Sciences, Inc
Man-Fung Yuen - Advisory Committees or Review Panels: GlaxoSmithKline,
Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Bristol-Myers Squibb, Pfizer,
GlaxoSmithKline, Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Bristol-Myers
Squibb, Pfizer; Grant/Research Support: Roche, Bristol-Myers Squibb,
GlaxoSmithKline, Gilead Science, Roche, Bristol-Myers Squibb, GlaxoSmith-
Kline, Gilead Science, Roche, Bristol-Myers Squibb, GlaxoSmithKline, Gilead
Science, Roche, Bristol-Myers Squibb, GlaxoSmithKline, Gilead Science
The following authors have nothing to disclose: Ka-Shing Cheung, Danny Wong
127
A New Clinically-Based Staging System for Distal Cholangiocarcinoma
Maria E. Lozada 1 , Jonggi Choi 1 , Roongruedee Chaiteerakij 1,2 ,
Ju Dong Yang 1 , Nasra H. Giama 1 , Steven Alberts 3 , Gregory J.
Gores 1 , Lewis R. Roberts 1 ; 1 Division of Gastroenterology and
Hepatology, Mayo Clinic College of Medicine, and Mayo Clinic
Cancer Center, Rochester, MN; 2 Department of Medicine, Faculty
of Medicine, Chulalongkorn University and King Chulalongkorn
Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand;
3 Division of Medical Oncology, Mayo Clinic College of Medicine,
and Mayo Clinic Cancer Center, Rochester, MN
Background: Clinical predictors of survival for each subtype of
cholangiocarcinoma, intrahepatic, perihilar and distal (dCCA)
are limited. Currently available staging systems can be used to
predict prognosis for resectable dCCA but are not relevant to
patients with unresectable disease. Based on these limitations,
we aimed to construct a clinical staging system that stratifies
dCCA patients. Methods: We identified 170 treatment-naïve
dCCA patients seen at Mayo Clinic, Rochester from January
1, 2000 through May 31, 2014. Data were retrospectively
abstracted from the electronic medical record. Overall median
survival (MS), the primary endpoint, was estimated using the
Kaplan-Meier method and compared using the log-rank test.
Cox-proportional hazards analysis was used to identify predictors
of survival. Performance of the staging system was assessed
using concordance index. Results: Of the 170 dCCA patients,
93 (58%) were male, the mean age was 67 years, and 19
(12%) had primary sclerosing cholangitis. The MS of the entire
cohort was 17.0 months (95% confidence interval [CI]: 14.0-
20.5). Baseline ECOG performance status, post-stenting CA
19-9 and disease extent were significantly associated with survival
and further incorporated into a 4-tier staging system. A
total of 143 patients were classified into the new staging system.
Overall MS for patients in Stage I, Stage II, Stage III and
Stage IV were 46.8, 14.3, 8.1, and 3.4 months, with hazard
ratios (95% CI) of 1.0 (ref.), 1.9 (1.0-3.4), 4.1 (2.3-7.0), and
9.7 (5.1-18.5), respectively. Concordance index for the new
staging system was 0.73. Conclusion: We have developed a
new staging system based on non-operative clinical variables
that classifies dCCA patients into 4 distinct stages with homogeneous
survival. Given the small cohort, validation to confirm
these findings is crucial. However, this staging system could
potentially be a key prognostic tool for better stratification of
patients enrolled in clinical trials of novel therapies for dCCA.
Disclosures:
Gregory J. Gores - Advisory Committees or Review Panels: Conatus
Lewis R. Roberts - Grant/Research Support: Bristol Myers Squibb, ARIAD Pharmaceuticals,
BTG, Wako Diagnostics, Inova Diagnostics, Gilead Sciences, Five
Prime Therapeutics