|OL05 Liver: Miscellaneous
|Selection of Presentations from Abstract Submissions
|OL05-03 ||Human ESC-derived Expandable Hepatic Organoids Enable Therapeutic Liver Repopulation and Pathophysiological Modeling of Alcoholic Liver Injury
Yunfang Wang, China
Y. Wang, X. Wang
Translational Medicine Research Center, Beijing Tsinghua Chang Gung Hospital, China
Here, we report the generation of human
ESC-derived, expandable hepatic organoids (hEHOs) enabling
therapeutic liver repopulation and pathophysiological
modeling of alcoholic liver injury.
The culture system including a mix of
A83-01, Forskolin, R-spondin 1, Wnt3a and EGF along with the extracellular
matrix was used to generate hEHOs. The liver repopulation potential of hEHOs was
assayed in FRG mouse model of inherited metabolic liver disorders. The tumorigenesis
and lineage restriction of hEHOs were evaluated by transplanting the hEHOs into
epididymal fat pads of NOD/SCID mice. To model alcoholic liver disease, a
derivative model by incorporating human fetal liver mesenchymal cells (hFLMCs)
into the hEHOs, referred
to as hFLMC/hEHO was generated and treated with 100mM ethanol
The hEHOs stably maintain phenotypic features of bipotential liver
stem/progenitor cells that can differentiate into functional hepatocytes or
cholangiocytes. The hEHOs can expand for 20 passages enabling large scale
expansion to cell numbers requisite for industry or clinical programs. The hEHOs
display remarkable repopulation capacity in injured livers of FRG mice
following transplantation. If implanted into the epididymal fat pads of
immune-deficient mice, they do not generate non-hepatic lineages and have no
tendency to form teratomas. The hFLMC/hEHO can model alcoholic liver
disease-associated pathophysiologic changes, including oxidative stress
generation, steatosis, inflammatory mediators release and fibrosis, under
The hEHOs have considerable potential to
be a novel, ex vivo pathophysiological model for studying alcoholic liver
disease as well as a promising cellular source for treating human liver
|OL05-04 ||Surgical Strategy for Future Remnant Liver Hypertrophy: Portal Vein Embolization vs. Liver Venous Deprivation
Mafalda Couto, France
M. Couto1, F. Gianonne1, B. Guiu2, F. Navarro1, F. Panaro1
1Division of HBP Surgery and Transplantation, Department of Surgery, St. Eloi Hospital, CHRU Montpellier, France, 2Division of Interventional Radiology, Department of Radiology, St. Eloi Hospital, CHRU Montpellier, France
Preoperative portal vein embolization (PVE) is the standard technique used
to increase the size of the future remnant liver
(FRL) before major hepatectomies. Another method to increase the FRL is liver venous deprivation (LVD), but its clinical and operative impact
is still unknown. The aim of this study
is to compare perioperative findings, morbidity and mortality and the increase
in FRL volume (FRL-V) and FRL function (FRL-F) between PVE and LVD.
Fifty-two patients undergoing PVE and LVD before a major hepatectomy were
retrospectively analyzed between 2015 and 2018. Intra-operative parameters,
postoperative complications and histological findings were compared. For the volumetric and functional assessment, we collected the results
from CT-scan and 99m-technetium (Tc)-Mebrofenin
hepatobiliary scintigraphy (HBS) realized at day 7th, 14th
and 21th after embolization procedure.
To induce FRL growth 25 patients underwent PVE and 23 LVD. No differences
between the two groups were found in terms of intraoperative bleeding (P=0.9),
hepatic pedicle clamping (P=0.46), intraoperative red blood cells transfusions
(P=0.42) and operative time (P=0.95). Post-operative course was similar when
comparing complications in the two arms (P=0.8). No difference in biliary leak
(P=0.27), hemorrhage (P=0.11) and liver failure
(P=0.6) was found. The two groups were also
similar in terms of FRL-V increase, but there was a significant difference in
favor of LVD group regarding the FRL-F increase at day 14th and 21th.
LVD technique seems to be feasible, well tolerated and provides fast and
important hypertrophy of the FRL, without influencing the morbidity and
mortality rate during and after major hepatectomy.
|OL05-05 ||Percentage Genome Change and Chromosome 7q Amplification Predict Sorafenib Response in Advanced Hepatocellular Carcinoma
Ming-Chin Yu, Taiwan, Republic of China
M.-C. Yu1,2, Q. Zhu3, C.-N. Tsai4, C.-W. Lee1
1Surgery, Chang-Gung Memorial Hospital, Taiwan, Republic of China, 2Surgery, New Taipei Municipal Tucheng Hospital, Taiwan, Republic of China, 3Surgery, Xiamen Chang Gung Hospital, China, 4Institute of Clinical Medical Sciences, Chang-Gung University, Taiwan, Republic of China
Background: Sorafenib is the first-line
treatment for advanced stage HCC, but its therapeutic efficacy is less than
50%. Biomarkers for predicting the therapeutic efficacy of sorafenib administration
to patients with advanced HCC are required. The role of chromosomal
copy number aberrations (CNAs) in patients with advanced HCC for with sorafenib were evaluated for drug response.
Methods: The response to sorafenib treatment of twenty-three HCC patients who developed
advanced recurrence after partial hepatectomy was analyzed using the modified Response Evaluation
Criteria in Solid Tumors (mRECIST). Formalin fixed paraffin embedded (FFPE) tissue
specimens obtained after tumor resection were analyzed using the Affymetrix
OncoScan® FFPE assay.
Results: From the 23 patients analyzed in this study, 7 (30.4%)
had complete/partial response to sorafenib (CR/PR), 7 (30.4%) had stable
disease (SD), and 9 (39.1%) had progressive disease (PD). The mean genome-wide percentage
of genome change acquisition via the OncoScan platform was 19.8% for patients
with CR/PR/SD and 50.02% in the PD group (P=0.055).
Percentage of genome change above 33% was associated with adverse outcomes for
sorafenib treatment in the time-to-progression analysis (P=0.007) and overall survival (P=0.096). Among these CNAs, amplification of chromosome 7q,
containing the multidrug resistance gene ATP
Binding Cassette Subfamily B Member 1 (ACBC1),
significantly associated with poor overall survival (P=0.004) and time-to-progression (P< 0.001).
Conclusions: Higher percentage genome change and amplification of chromosome
7q in advanced HCC is associated with sorafenib resistance.
|OL05-06 ||Liver Stiffness-Based Model Predicts Hepatic Venous Pressure Gradient in Patients Undergoing Hepatectomy and Liver Transplantation
Muthukumarassamy Rajakannu, India
M. Rajakannu1, A. Coilly2, D. Cherqui2, D. Castaing2, A. Sa Cunha2, R. Adam2, D. Samuel2, E. Vibert2
1Centre Hepato Biliaire, Hopital Paul Brousse, France, 2Centre Hépato-Biliaire, AH-HP Hôpital Paul Brousse, France
Background: Invasive hepatic venous pressure gradient (HVPG) measurement is the gold standard test to assess portal hypertension. The aim was to develop a model predictive of clinically significant portal hypertension (HVPG≥10mmHg) using pre-operative noninvasive makers.
Methods: 161 patients [66% men, median age of 63 years] who have been planned for liver resection/transplantation were enrolled prospectively and preoperative liver stiffness measurement (LSM), liver function test, and intraoperative HVPG were performed.
Results: Median LSM, and HVPG were 9.5kPa, and 5mmHg respectively. No underlying liver disease (F0/1), chronic liver disease (F2/3), and cirrhosis (F4) were found in 32.9%, 32.9% and 34.2% patients respectively. The study cohort was randomly divided into training [n=106] and validation [n=55] sets. Independent predictors of HVPG≥10mmHg in the training set, LSM [p< 0.01, OR=1.1], total bilirubin [p=0.04, OR=0.9], alkaline phosphatase [p=0.02, OR=1], and international normalized ratio [p< 0.01, OR=41.4], were used to develop a probability score model called HVPG10score. Area under receiver operating curve in the training and internal validation sets were 0.91 [95%CI:0.83-0.98] and 0.93 [95%CI:0.86-0.99] respectively with a cutoff of 0.15. HVPG10score was calculated by multiplying the probability by 100. In the overall cohort, HVPG10score of 15 would predict the individual risk of HVPG≥10mmHg with 83% accuracy, 90% sensitivity, 81% specificity and 96% negative predictive value.
Conclusions: HVPG10score is an easy-to-use noninvasive continuous scale tool to predict HVPG≥10mmHg. A score < 15 would accurately rule out the need for esophageal varices screening and risk of decompensation in >95% chronic liver disease patients.