Oral (pre-recorded)
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

Introduction: Here, we report the generation of human ESC-derived, expandable hepatic organoids (hEHOs) enabling therapeutic liver repopulation and pathophysiological modeling of alcoholic liver injury.
Methods: 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 for 7days.
Results: 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 ethanol treatment.
Conclusion: 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 diseases.
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.