studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 443A
463
Progranulin Autoantibodies and Genetic Variation in
Patients with Cholangiocarcinoma
Vincent Zimmer 1 , Lorenz Thurner 2 , Monica Acalovschi 3 , Michael
Pfreundschuh 2 , Frank Lammert 1 ; 1 Department for Medicine II, Saarland
University Medical Center, Homburg, Germany; 2 Department
of Medicine I, Saarland University Medical Center, Homburg, Germany;
3 Department of Medicine III, University Iuliu Hatieganu,
Cluj-Napoca, Romania
Background: Recently, the novel growth factor and TNF signalling
adaptor progranulin (PGRN) has been implicated in
the inflammation-driven pathogenesis of cholangiocarcinoma
(CCA).(1,2) Neutralizing PGRN autoantibodies have been
described in autoimmune diseases, including inflammatory
bowel disease (IBD).(3,4) Therefore, our aim now was to
assess PGRN autoantibody incidence and potential effects of
the common PGRN gene variant rs5848 (known to be associated
with reduced PGRN serum concentrations) on susceptibility
and PGRN autoantibody formation in a large European
CCA population.(5) Patients & Methods: Overall, 221 individuals
with CCA (males n = 131, age 66 ± 11 years) originating
from Germany (n = 164) and Romania (n = 57) and 295
CCA-free control individuals were genotyped. The common
non-synonymous single nucleotide polymorphism (SNP) rs5846
was genotyped by PCR-based assays with 5’-nuclease and
fluorescence detection (TaqMan). PGRN autoantibodies were
determined by ELISA.(4) Results: rs5848 genotype frequencies
in the control group were consistent with the Hardy-Weinberg
equilibrium (HWE), with a call rate > 99 % indicating robust
genotyping. The association tests did not provide evidence
for genetic CCA risk modulation by the PGRN variant (Odds
ratio = 0.92; 95 % confidence interval = 0.71-1.19; P>0.05).
Seven of 61 patients (11.5%) tested positive for PGRN autoantibodies,
with no significant sex differences (3/32 males, 4/29
females). Considering rs5848 variation in the subgroup with
available PGRN autoantibody status, no significant differences
in allele and genotype distribution were observed. Conclusions:
Our preliminary data indicate PGRN autoantibodies as a novel
potential tumor antigen in a defined subset of CCA patients.
Extension of the current study in larger sample sizes and delineation
of potential implications in terms of CCA subtypes and
prognostic relevance of PGRN autoimmunity is warranted. References:
1. Frampton et al. Gut 2012 2. Frampton et al. Am
J Physiol Gastrointest Liver Physiol 2012 3. Thurner et al. J
Autoimmun 2013 4. Thurner et al. Dig Dis Sci 2014 5. Hsiung
et al. J Neurol Sci 2011
Disclosures:
The following authors have nothing to disclose: Vincent Zimmer, Lorenz Thurner,
Monica Acalovschi, Michael Pfreundschuh, Frank Lammert
464
The effect of additional transarterial chemoembolization
after combined chemoradiation therapy for locally
advanced hepatocellular carcinoma with portal vein
thrombosis
Ja Kyung Kim, Jung Il Lee, Jun Won Kim, Ik Jae Lee, Seung-Moon
Joo, Kwang-Hun Lee, Eun-Suk Cho, Tae Joo Jeon, Jae Keun Kim,
Nomi Park, Ah-Young Kang, Kwan Sik Lee; Yonsei University College
of Medicine, Seoul, Korea (the Republic of)
Backgrounds: Combined chemoradiation therapy (CCRT) followed
by intraarterial chemotherapy (IAC) has been reported
to be beneficial for locally advanced hepatocellular carcinoma
(HCC) with portal vein thrombosis (PVT). However, hepatic
arterial chemoembolization (TACE) was generally not accepted
for this situation. The aim of this study is to evaluate the role of
adding TACE instead of IAC after CCRT. Methods: Thirty-seven
patients were treated by CCRT as the initial treatment for HCC
with PVT between 2009 and 2014. IAC through hepatic arterial
chemoport and intermittent TACE (Group A) followed in
18 patients and only IAC were repeated in 19 patients (Group
B). We excluded the patients who had extra-hepatic metastasis,
active peptic ulcer, and inadequate hepato-renal function.
For CCRT, infusion of 5-FU (500 mg/day) via chemoport
was given during the first and last five days of external radiation
therapy (RTx) for 5 weeks. For IAC, infusion of cisplatin
(70~100mg/m2 for one day) with 5-FU (750~1000mg for
3 days) was repeated monthly. Results: Mean age was 55
year; male to female was 32 to 5. Underlying liver diseases
were hepatitis B, hepatitis C and non-B/C in 26, 2 and 10
patients, respectively. Mean follow-up duration was 14 months
(3-65 months). The objective response (CR+PR) rates in tumor
size after 1 month after CCRT were 45.9%. The mean level
of αFP after 1 month after CCRT were decreased in 81% of
patients. During follow up, complete response was noted in
3 patients. One patient underwent resection for cure. Median
overall survival duration was 12.4 months. Overall survival of
group A was significantly better than that of group B (mean
42.5 vs. 12.2 months, p=0.001). Conclusion: Adding intermittent
transarterial chemoembolization contributed survival gain
following combined chemoradiation therapy for advanced
hepatocellular carcinoma with portal vein thrombosis. Further
prospective randomized study comparing TACE with TAC after
CCRT is warranted.
Disclosures:
The following authors have nothing to disclose: Ja Kyung Kim, Jung Il Lee, Jun
Won Kim, Ik Jae Lee, Seung-Moon Joo, Kwang-Hun Lee, Eun-Suk Cho, Tae Joo
Jeon, Jae Keun Kim, Nomi Park, Ah-Young Kang, Kwan Sik Lee
465
Clinicopathologic analysis of patients with HBV-positive,
HCV-positive and non-B non-C hepatocellular carcinomas
Jun Akiba 1 , Osamu Nakashima 2 , Yoshiki Naito 1 , Hironori
Kusano 1 , Reiichiro Kondo 1 , Hirohisa Yano 1 ; 1 Department of
Pathology, Kurume University School of Medicine, Kurume, Japan;
2 Department of Clinical Laboratory Medicine, Kurume University
Hospital, Kurume, Japan
[aim] The chronic infection of hepatitis B virus (HBV) and hepatitis
C virus (HCV) is strongly associated with HCC. However,
recent developments of anti-viral treatments for HBV and HCV
contribute to reduce virus-associated HCC. On the other hand,
HCCs, which are negative for both hepatitis B surface antigen
(HBs-Ag) and anti-hepatitis C antibody (HCV-Ab), are increasing
in number in developed nations. The aim of this study is
to clarify the clinicopathologic features of surgically resected
HCCs with different etiologies. [Materials and methods] Surgically
resected 1430 cases (1598 nodules) at our hospital from
1991 to 2013 were enrolled in this study. All cases did not
have any previous treatments for HCC. HBV-related HCC (HBV-
HCC) and HCV-related HCC (HCV-HCC) were defined as positive
for serum HBs-Ag and serum HCV-Ab, respectively. Non
HBV and non HCV-related HCC (NBNC-HCC) was defined
as negative for both HBs-Ag and HCV-Ab. The cases which
were positive for both HBs-Ag and HCV-Ab were excluded.
Clinicopathologic features were compared. [Results] Out of
1430, 253, 949 and 228 cases were HBV-HCC, HCV-HCC
and NBNC-HCC, respectively. Patient age of HBV-HCC (55.8)
was significantly younger than those of HCV-HCC (67.6) and
NBNC-HCC (68.5). Tumor size was the smallest in HCV-HCC