studies

840A AASLD ABSTRACTS HEPATOLOGY, October, 2015
The mean body mass index (BMI) at transplant was 27±4.2kg/
m 2 with mean albumin 2.96±0.8g/dL. The mean TPA was
927.1±280mm 2 , which is much lower than the expected normal
mean of 1211.9±242.3mm 2 . During the study time period,
13 (54%) patients died at a mean of 1.2±2 years. Conclusion:
Although LVSD is an uncommon complication post-LT, patients
with high MELD and malnutrition maybe at highest risk. Sarcopenia,
measured by TPA, maybe a better marker for malnutrition
than traditional markers. BMI can be falsely elevated by
volume overload, which can explain the normal BMI seen in
our patient group. Sarcopenia should be studied further as a
possible predictor for LVSD. Pre-operative nutritional optimization
and close post-LT echocardiogram monitoring is advisable
in this population at risk for increased mortality post-LT.
Disclosures:
The following authors have nothing to disclose: Arun Mathew, She-Yan Wong,
Michael Cheung, Flavius Guglielmo, Cataldo Doria, David A. Sass, Dina Halegoua-De
Marzio
1277
Risk Stratification for Optimal Timing of Liver Transplantation
Following Repeated Locoregional Therapies in
Patients With Hepatitis B-Related Hepatocellular Carcinoma
Hwi Young Kim 1 , Won Kim 1 , Yong Jin Jung 1 , Hyeyoung Kim 2 ,
Nam-Joon Yi 2 , Kwang-Woong Lee 2 , Hae Won Lee 3 , Kyung-Suk
Suh 2 ; 1 Department of Internal Medicine, Seoul National University
Boramae Medical Center, Seoul, Korea (the Republic of); 2 Department
of Surgery, Seoul National University Hospital, Seoul, Korea
(the Republic of); 3 Department of Surgery, Seoul National University
Boramae Medical Center, Seoul, Korea (the Republic of)
BACKGROUND: Decision of timing for liver transplantation (LT)
in patients with HCC often depends on the responses to pre-LT
locoregional therapies especially in cases of organ shortage.
However, prediction of favorable tumor biology before LT
is difficult, and supporting data for decision of LT timing is
scarce. The aims were to prognosticate HCC patients who
underwent LT according to their responses to pre-LT locoregional
therapies, and to shed light on the decision of optimal
timing for LT. METHODS: Between January 2005 and
December 2011, a total of 264 patients with hepatitis B-related
HCC underwent LT. Excluding 52 patients with their
tumors beyond Milan criteria, 212 patients were included.
Responses to pre-LT locoregional therapies were assessed using
the modified RECIST criteria. Pre-LT risk scores were generated
as follows: [(No. of recurrence following radiofrequency
ablation or ethanol injection + 2x(No. of progressive disease
following transarterial chemoembolization(TACE)) + (No. of
recurrence following previous response to TACE)]. Cox proportional
hazard model was used to investigate prognostic
factors for recurrence-free survival. RESULTS: Median age at
the time of HCC diagnosis was 51 years, and male patients
were 81.1%. Median time to LT was 6.5 months(interquartile
range(IQR), 1.3-27.6). Median follow-up duration after LT
was 55.3 months(IQR, 39.6-81.4). Median maximal diameter
of the largest tumor was 2.0cm(range, 1.1-5). Hepatitis
B viral DNA was 1875 IU/mL(median) at baseline. Baseline
serum alpha-fetoprotein was 19 ng/mL(range, 1.8-23200).
Baseline Child-Pugh classes were A in 101(47.6%) and B in
61(28.8%), respectively. Before LT, 68 patients received at
least one session of radiofrequency ablation or ethanol injection,
and 100 patients received at least one session of TACE,
respectively. Overall, 127 patients(59.9%) received pre-LT
locoregional therapies. Pre-LT risk scores were as follows: 0,
n=126(59.4%); 1-2, n=36(17.0%); 3-5, n=30(14.2%); ≥6,
n=20(9.4%). From multivariable Cox analysis, pre-LT risk
scores and maximal tumor diameter were independently significant
prognostic factors for recurrence-free survival: risk score
0vs.1-2, hazard ratio(HR)=1.422(95% confidence interval(CI),
0.523-3.867), P=0.490); 0vs.3-5, HR=2.424(95%CI, 0.922-
6.369; P=0.072); 0vs.≥6, HR=4.805(95%CI, 1.782-12.957;
P=0.002); maximal diameter, HR=1.514(95%CI, 1.097-
2.090; P=0.012). CONCLUSION: Increasing pre-LT risk score
may represent a warning signal toward prompt LT rather than
repeated locoregional therapies, especially in case of score≥6.
Pre-LT risk score could be used as a surrogate marker of tumor
biology for the decision of LT timing.
Disclosures:
Kwang-Woong Lee - Grant/Research Support: ChongGeunDang, Astellas,
GreenCross
The following authors have nothing to disclose: Hwi Young Kim, Won Kim, Yong
Jin Jung, Hyeyoung Kim, Nam-Joon Yi, Hae Won Lee, Kyung-Suk Suh
1278
Synergistic anticancer effect of metformin in combination
with immunosuppressant on hepatocellular carcinoma
cell lines
Suk-Won Suh 1 , Kwang-Woong Lee 2 , Yoo-Shin Choi 1 ; 1 Department
of Surgery, Chung-Ang University College of Medicine, Seoul,
Korea (the Republic of); 2 Seoul National University College of
Medicine, Seoul, Korea (the Republic of)
After liver transplantation (LT), immunosuppression is needed
to avoid rejection and graft loss, however, it can stimulate
hepatocellular carcinoma (HCC) recurrence and progression.
Previous studies have shown that metformin had an anticancer
effect on several cancers, including HCC. The aim of this
study was to evaluate the interactions between metformin and
immunosuppressive agents including sirolimus, tacrolimus and
mycophenolate mofetil (MMF) for antitumor activity. Three cell
lines (Huh7, HepG2 and Hep3b) were tested. Cell viability
was determined using a MTT assay and Western blot analysis
for mammalian target of rapamycin (mTOR) pathway related
proteins were performed to reveal their mechanism. Metformin
and sirolimus had synergistic antiproliferative effect and sirolimus
plus metformin supplemented with MMF also showed
synergistic antiproliferative effect in specific HCC cells. Synergistic
effect of metformin and sirolimus through the inhibition
of mTOR and its down-stream, p70S6K, and p-4EBP1 were
demonstrated. Metformin and sirolimus also showed synergistic
effect for the down-regulation of Livin and Survivin expressions
in HepG2 and Hep3b cells. In conclusion, metformin had synergistic
interactions with sirolimus in terms of anticancer effects
for HCC cells and the mechanism explaining this synergistic
inhibition might be related with mTOR pathway. These results
may provide a foundation for further studies for patients with
HCC who underwent LT in clinical era.
Disclosures:
Kwang-Woong Lee - Grant/Research Support: ChongGeunDang, Astellas,
GreenCross
The following authors have nothing to disclose: Suk-Won Suh, Yoo-Shin Choi