studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 415A
therapy. Age < 50 years and HBV DNA ≥ 2000 IU/mL were
independent risk factors for HBV DNA elevation. Conclusion
HBV DNA elevation after resection increases the risk of HCC
recurrence irrespective of preoperative antiviral therapy. However,
HBV DNA elevation is an independent risk factor for
recurrence in patients without preoperative antiviral therapy.
Therefore, perioperative antiviral therapy should be considered
to prevent HBV DNA elevation and recurrence, especially in
patients with Age < 50 years and/or HBV DNA ≥ 2000 IU/
mL.
Disclosures:
Kwan Soo Byun - Grant/Research Support: Gilead, BMS
The following authors have nothing to disclose: Yang J. Yoo, Ji Hoon Kim, Seong
Hee Kang, Young-Sun Lee, Tae Suk Kim, Sang Jun Suh, Young Kul Jung, Yeon
Seok Seo, Hyung Joon Yim, Jong Eun Yeon
survival (P = 0.024). Conclusions: Gene alterations in TERT
promoter, TP53, CTNNB1, and HBV integration were closely
associated with HCC development, and mutations in TERT promoter
are related to poor prognosis. These results are useful for
understanding the underlying mechanism of hepatocarcinogenesis,
diagnosis, and predicting outcomes of patients with HCC.
Disclosures:
Sei Kakinuma - Grant/Research Support: The Japanese Society of Gastroenterology,
MSD Co., Ltd.
Mamoru Watanabe - Grant/Research Support: MSD Co., Ltd.
The following authors have nothing to disclose: Fukiko Kawai-Kitahata, Yasuhiro
Asahina, Shinji Tanaka, Miyako Murakawa, Sayuri Nitta, Takako Watanabe,
Satoshi Otani, Fumio Goto, Hiroko Nagata, Shun Kaneko, Seishin Azuma,
Yasuhiro Itsui, Mina Nakagawa, Minoru Tanabe, Shinya Maekawa, Nobuyuki
Enomoto
406
Comprehensive analyses of mutations and hepatitis B
virus integration in hepatocellular carcinoma with clinicopathological
features
Fukiko Kawai-Kitahata 1 , Yasuhiro Asahina 1 , Shinji Tanaka 1 , Sei
Kakinuma 1 , Miyako Murakawa 1 , Sayuri Nitta 1 , Takako Watanabe
1 , Satoshi Otani 1 , Fumio Goto 1 , Hiroko Nagata 1 , Shun
Kaneko 1 , Seishin Azuma 1 , Yasuhiro Itsui 1 , Mina Nakagawa 1 ,
Minoru Tanabe 1 , Shinya Maekawa 2 , Nobuyuki Enomoto 2 ,
Mamoru Watanabe 1 ; 1 Tokyo Medical and Dental University,
Tokyo, Japan; 2 University of Yamanashi, Yamanashi, Japan
Background & Aims: Genetic alterations in specific genes
are critical events in carcinogenesis and hepatocellular carcinoma
(HCC) progression. However, the genetic alterations
responsible for HCC development, progression, and survival
are unclear. Methods: The extracted DNA from 104 patients
was amplified by multiplexed PCR targeting 54 cancer-related
genes containing 2820 mutational hotspots. The mutations
were analyzed using a semiconductor-based DNA sequencer.
Nucleotide variants that were detected in tumors and absent
in corresponding non-tumor tissue were determined as somatic
mutations. We also investigated TERT promoter mutation at
2 hot spots through direct sequencing. HBV oligonucleotide
probes were designed primarily within the conserved regions
of different HBV strains including genotypes Aa, Ae, Ba, Bj,
and C. After incubation with custom capture oligos, hybridized
fragments were sequenced on a MiSeq instrument generating
300 bp paired-end reads. Results: We found recurrent
mutations in several genes such as TERT (65%), TP53 (38%),
CTNNB1 (30%), AXIN1 (2%), PTEN (2%), and CDKN2A
(2%). TERT promoter mutations were associated with older
age (P = 0.005), presence of hepatitis C virus (HCV) infection
(P = 0.003), and absence of hepatitis B virus (HBV) infection
(P < 0.0001). In patients with hepatitis B surface antigen
(HBsAg) positive, a total of 78 HBV integration breakpoints
were detected in 25/27 (92.6%) patients. Most (89%) of HBV
integrant was the HBx region. HBV integration was frequently
found in particular genes including TERT (n = 9), KMT2B (MLL4;
n = 2), and MYO7A (n = 2). Seven (77.8%) of TERT locus
breakpoints were paired with HBx gene, all at the 3’-end of
HBx gene. HBV integration into TERT locus was mutually exclusive
to TERT promoter mutations. The HBV integration number
was significantly associated with HCC at younger age (Spearman’s
rank order correlation, r s
= −0.5342, P < 0.01). TP53
mutations were associated with HBV infection (P = 0.0001)
and absence of HCV infection (P = 0.002). CTNNB1 mutations
were associated with absence of HBV infection (P = 0.010).
Moreover, TERT promoter mutation was significantly associated
with shorter disease-free survival (P = 0.005) and poor overall
407
Treatment not needed for hypovascular tumors associated
with hepatocellular carcinoma
Yutaka Midorikawa, Tadatoshi Takayama; Nihon Univ., Tokyo,
Japan
Aim: Hypovascular tumors associated with hepatocellular
carcinoma (HCC) can be diagnosed, but it remains unknown
whether such lesions should be treated immediately after diagnosis.
This study aimed to clarify whether treating hypovascular
liver nodules contributes to the prolongation of patient survival,
and sought to directly calculate a lead time from the diagnosis
of hypovascular liver nodules to their transformation into
hypervascular HCC. Methods: One hundred and four patients
with hypovascular liver nodules smaller than 3 cm underwent
liver resection immediately after diagnosis (Group 1), while
80 patients with hypovascular liver nodules were treated after
appearance of vascularization or other hypervascular HCC
lesions on imaging studies (Group 2). To avoid lead-time bias
for tumor vascularization, the survival rates of patients after
diagnosis of hypovascular liver nodules as well as the survival
rates after liver resection in the two groups were compared.
Results: After a median follow-up period of 3.3 years (range,
0.6–11.2), the median overall survival rates “after liver resection”
were 9.7 years (95% confidence interval [CI], 6.7–11.9)
and 8.5 years (4.8–12.1; P = 0.017), respectively, and recurrence-free
survivals were 3.8 years (95% CI, 2.7–6.3) and 1.9
years (1.5–2.9; P