studies

384A AASLD ABSTRACTS HEPATOLOGY, October, 2015
This study examined how brain death affects preconditioned
steatotic liver grafts undergoing transplantation. Methods: Steatotic
grafts from non-brain dead and brain dead-donors were
cold stored for 6 hours and then transplanted. After 4 hours of
reperfusion, hepatic damage was analyzed. Two strategies,
acetylcholine pre-treatment and ischemic preconditioning or
the combination of them were evaluated and their underlying
mechanisms were characterized. Results: The presence
of brain dead exacerbated hepatic damage in steatotic liver
since increased transaminase levels and damage score in
comparison with the liver transplantation group. Acetylcholine
treatment reduced hepatic damage after liver transplantation
in brain dead donors, through PKC, increased antioxidants
and reduced lipid peroxidation, nitrotyrosines and neutrophil
accumulation,. On the other hand, preconditioning benefits in
non-brain dead donors were associated with nitric oxide and
acetylcholine generation. In brain dead donors, preconditioning
generated nitric oxide but did not promote acetylcholine
up-regulation, and this resulted in inflammation and damage.
Conclusions: We suggest that the combination of acetylcholine
treatment and preconditioning conferred stronger protection
against damage, oxidative stress and neutrophil accumulation
than acetylcholine treatment alone. These superior beneficial
effects were due to a selective preconditioning-mediated
generation of nitric oxide and regulation of PPAR and TLR4
pathways, which were not observed when acetylcholine was
administered alone. We herein propose that the time frame
between the declaration of brain dead and organ retrieval
provides an important window for cytoprotective intervention,
which may counteract the detrimental effects of brain dead.
Consequently, our findings show that the combination of acetylcholine
and preconditioning as a feasible and a protective
strategy to reduce the adverse effects of brain dead and to
improve the quality of liver grafts.
Disclosures:
The following authors have nothing to disclose: Mónica B. Jiménez-Castro, Mariana
Mendes-Braz, Jordi Gracia-Sancho, Maria Eugenia Cornide-Petronio, Araní
Casillas-Ramírez, Juan Rodes, Carmen Peralta
343
WITHDRAWN
344
Survival After Intra-Arterial Treatment for Hepatocellular
Carcinoma: Impact of Liver Dysfunction and Development
of a Predictive Statistical Model: an International
Collaborative Project
Imam Waked 1 , Sarah Berhane 2 , Stephen L. Chan 3 , Asmaa
Gomaa 4 , Mercedes Iñarrairaegui 5 , Zahraa Alkhatib 4 , Takashi
Kumada 6 , Paul B. Lai 7 , Tim Meyer 8 , Frankie Mo 3 , Daniel Palmer 2 ,
Bruno Sangro 5 , Nicholas Stern 9 , Toshifumi Tada 6 , Hidenori
Toyoda 6 , Arndt Vogel 10 , Winnie Yeo 3 , Phillip Johnson 2 ; 1 Hepatology,
National Liver Institute, Menoufiya, Egypt; 2 Molecular
and Clinical Cancer Medicine;, University of Liverpool, Liverpool,
United Kingdom; 3 Sir Y. K. Pao Centre for Cancer, Chinese University
of Hong Kong, Hong Kong, China; 4 Oncology, National
Liver Institute, Shebeen El Kom, Egypt; 5 Centro de Investigacion
Biomedica en Red de Enfermedades Hepaticas y Digestivas, Clinica
Universidad de Navarra, Pamplona, Spain; 6 Ogaki Municipal
Hospital, Ogaki, Japan; 7 Surgery, The Chinese University of Hong
Kong, Hong Komg, China; 8 Oncology, University College of London
Cancer Institute, London, United Kingdom; 9 Gastroenterology,
Aintree University Hospital, Liverpool, United Kingdom; 10 Hannover
Medical School, Hannover, Germany
Background: TransArterial Chemo-Embolisation (TACE) is recommended
for patients with BCLC intermediate stage HCC
(stage B) particularly in patients with excellent underlying liver
function and minimal symptoms. A recently developed measure
of liver function (the Albumin-Bilirubin (ALBI) grade) now permits
detailed assessment of the impact of liver function on survival
(1). Methods: We accrued patient level data from 2454
patients undergoing TA(C)E – China (n= 242), Japan (n=655),
Europe (UK, Germany and Spain combined, n=559 ) and
Egypt (n=998). Overall, 59 % had Child-Pugh grade ‘A’ and
17%, portal vein invasion. Liver function was graded according
to their ALBI grade. A statistical model for survival after
TA(C)E was built on a randomly selected half of a combined
group of 1214 Japanese and European patients, n=602 (323
Japanese and 279 European) and then validated the on the
remaining 612 patients (332 Japanese and 280 European).
The TACE model was also validated on an independent cohort
from Egypt (n=998). Results: Our TACE model accurately predicted
survival in the second half validation set (actual median
survival = 20.4 months, predicted = 20.7 months) as well as
in the Egyptian cohort (actual median survival = 18 months,
predicted = 20 months). One year survival was 65.7 and
71.3% for actual and predicted respectively). Classification of
patients according their ALBI grade resulted in clear, non-overlapping
survival curves in all cohorts (figure) Conclusion: ALBI
categorised patients receiving TACE into three clear prognostic
groups. Our TACE model accurately predicted survival on the
basis of baseline clinical and laboratory features. References
1. Johnson PJ et al., J Clin Oncol. JCO.2014.57.9151