studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1033A
a Sendai virus vector expressing Yamanaka factors. To examine
whether these iPSCs expressed pluripotent markers, realtime
RT-PCR and immunostaining analyses were performed.
The iPSCs were then differentiated into hepatocyte-like cells.
To examine the BSEP expression levels in HLCs derived from
BD-iPSC (BD-iPS-HLCs) and their biliary excretion capacity, we
performed real-time RT-PCR, immunostaining analyses, and
cholyl-lysyl-fluorescein (CLF) excretion experiments. Results: We
successfully obtained iPSCs from blood cells. These cells were
positive for OCT4 and expressed markers specific to human
embryonal stem cells. The HLCs were obtained on day 25 after
hepatocyte differentiation. Bile canaliculi between the cells
were observed by electron microscopy. BSEP was expressed
in the membranes of Control-iPSC derived HLCs (Control-iPS-
HLCs), while BD-iPS-HLCs did not show localized expression of
BSEP in its membranes. The accumulation of CLF in bile canaliculi
was observed in Control-iPS-HLCs, but not in BD-iPS-HLCs,
suggesting that the biliary excretion capacity was impaired
in BD-iPS-HLCs. Thus, the data implied that BD-iPS-HLCs could
reproduce the pathophysiology of PFIC2. Conclusions: BD-iPS-
HLCs recapitulated the PFIC2 phenotype, mislocalization of
BSEP, and impairment of biliary excretion. Thus, this PFIC2
model can be applied to elucidate disease mechanisms and to
determine novel therapeutic options.
Disclosures:
The following authors have nothing to disclose: Kazuo Imagawa, Kazuo
Takayama, Shigemi Isoyama, Ken Tanikawa, Masato Shinkai, Masayoshi Kage,
Kenji Kawabata, Ryo Sumazaki, Hiroyuki Mizuguchi
1691
King’s-Variceal Prediction Score (K-VaPS); a non invasive
assessment tool of severe portal hypertension in
cirrhotic children
Peter Witters, Dominic A. Hughes, Palaniswamy Karthikeyan,
Alastair J. Baker, Mark Davenport, Anil Dhawan, Tassos Grammatikopoulos;
Paediatric Liver GI & Nutrition Centre, King’s College
Hospital NHS Foundation Trust, London, United Kingdom
Background & aim: Variceal hemorrhage is a serious complication
of chronic liver disease(CLD) in children. There is limited
knowledge around the best prophylactic management and
selection criteria of children undergoing surveillance endoscopy
(OGD). We derive a new prediction model of clinically
significant varices (CSV) and validate it in a separate cohort.
Methods: All patients presenting in our centre with suspected
PHT or gastrointestinal (GI) bleeding due to CLD and undergoing
a first OGD between January 2005- December 2012 were
included. A validation cohort from 2013-2015 was obtained.
Clinical, biochemical and radiological data were collected.
Results: Data on 124(67M) treatment-naïve patients were collected.
Mean age was 8.81 ± 5.60 years. 50% had biliary
atresia and the remainder various other CLD types. 35(28%)
presented with GI bleeding and overall 79(64%) were in
CSV+ve. Mean values in CSV+ve vs. CSV-ve group were for
haemoglobin(Hb)(mg/dL) [10,58 vs. 11,62 p=0.008], platelet
count(10 9 /ml) [111 vs. 167, p=0.001], white cell count(10/
ml) [5.3 vs. 6.9, p=0.019], INR[1.22 vs. 1.13, p=0.004], bilirubin(mg/dL)
[53.33 vs. 28.22, p=0.014], albumin(g/L) [37
vs. 41, p=0.0001], AST(IU/L) [121 vs. 104, p=0.815], spleen
size(cm) [16.41 vs. 14.49, p=0.073], spleen size(z-score)
[9.1 vs. 6.35, p=0.009] and equivalent adult spleen size(E-
ASS) (cm) [23.21 vs. 19.3, p=0.003], respectively. Previously
published predictions rules had, at optimal cut-off, a sensitivity
and specificity of 76% and 59%(CPR), 60% and 55%(APRI),
80% and 59%(VPR), respectively. To construct a new prediction
score Pearson’s bivariate correlation was performed.
Variables significantly correlating with CSV were Hb(R=-.250,
p= 0.005), platelet count(R=-.276, p=0.002), INR(R=0.223,
p=0.010), albumin(R=-.334, p