Day 2 :
Keynote Forum
Prof. Higinio T. Mappala
José R. Reyes Memorial Medical Center, Philippines
Keynote: The efficacy of bile acids in the treatment of non-alcoholic steatohepatitis: A 10-year systematic review
Biography:
Higinio T Mappala is a Full-time Medical Specialist III and Administrator at the Jose Reyes Memorial Medical Center, Manila, Philippines and has served as a University Professor and Dean of 2 Medical Schools. He has attended the 3-level training courses on Leadership and Management by the World Gastroenterology Organization held in Florida, USA, Dubrovnic, Croatia and Porto, Portugal. He is a focused lecturer on NAFLD in local and international conventions.
Abstract:
Non-alcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease which may progress to non-alcoholic steatohepatitis (NASH). Currently there are no therapeutic strategies for such disease. Only lifestyle modification through diet and exercise were proven to afford some benefit in patients with NAFLD. No pharmacologic agents have so far been approved for the treatment of NAFLD or NASH. Therefore, most clinical efforts have been directed at treating the components of metabolic syndrome, namely obesity, diabetes, hypertension and dyslipidemias. Other interventions are directed at specific pathways potentially involved in the pathogenesis of NAFLD, such as insulin resistance, oxidative stress, pro-inflammatory cytokines, apoptosis, bacterial overgrowth and angiotensin pathway. This lecture aims to show the potential of bile acids as a promising therapeutic option for NAFLD. This is a 10-year Systematic Review of the effects of bile Acids on non-alcoholic fatty liver disease (NAFLD). Bile Acids may yet prove to be an effective targeted treatment for non-alcoholic fatty liver disease.
Keynote Forum
Prof. Vladimir Subbotin
University of Pittsburgh, USA University of Wisconsin, USA
Keynote: Metastatic pattern of hepatocellular carcinoma: A hypothesis on privileged portal metastasis in light of co-evolution of an insulin-carrying portal system and the liver in chordate phylogeny
Biography:
Vladimir M Subbotin has studied Biology and Medicine at the Novosibirsk Medical School, Russia and has received MD degree in 1969. He has received his PhD in 1973 on the study of human placenta. Later he worked at the Russian Academy of Sciences, Siberian Division and as a volunteer at the Novosibirsk Zoo. His work includes experimental and theoretical approaches to cancer treatment and analysis of normal diseased morphogenesis in light of organ phylogeny.
Abstract:
Hepatocellular carcinoma (HCC) paradoxically metastasizes to portal veins 6-10 times more frequently than to hepatic veins. Accepted models of HCC vascular invasion, local dissemination and hematogenous spread, assume the likelihood of preferential metastasis into hepatic veins, and fail to explain the paradox. Reports on HCC presenting only as tumors of main portal veins with no detectable parenchymal HCC, emphasize the paradox. Assumption of hepatofugal flow does not resolve the paradox because the main trunk and first/second-order branches of portal veins are affected more often (4-6 times) than regions distal to the second-order branches of the portal vein. The author explains the portal HCC paradox as a phenomenon of privileged metastasizing proposed by Stephen Paget in 1889 in the seed and soil hypothesis. The author hypothesize that privileged HCC portal metastasis is due to high levels of insulin-like growth factors in the portal blood proximal to the liver, which constitutes the soil, while blood-circulating HCC cells became appropriate seeds after exposure to portal blood. Liver hepatocytes extract/consume these growth factors, creating less favorable conditions for metastasis in the hepatic vein. The author suggest that the portal vein environment, enriched by pancreatic growth factors, further facilitates the selection of more aggressive HCC clones from portal metastases, explaining the worse outcome in patients with a portal pattern. The author discern the origin of this phenomenon in evolution of portal vein/Langerhans’ islets/liver systems in chordate. Author hypothesize that the transition of expression pancreatic family hormones from neural cells to intestinal epithelial cells together with attaining portal system in amphioxus-like chordate ancestral invertebrate chordate predestinated liver evolution in vertebrates and determined the dependence of hepatocytes and hepatocyte-derived cells (HCC) on insulin-like growth factors. The author hypothesize that amphioxus’ hepatic diverticulum/portal system evolved from a yolk sac of an advanced chordate ancestor, the phylogeny suggested earlier by A S Romer.
Keynote Forum
Dr.Vikas Leelavati Balasaheb Jadhav
Dr.D.Y.Patil University, Pune, Maharashtra, India
Keynote: TransAbdominal Sonography of the Gall Bladder & its Hepatic & Peritoneal Perforations
Biography:
Dr.Vikas Leelavati BalaSaheb Jadhav has completed PostGraduation in Radiology in 1994. He has a 23 Years of experience in the field of Gastro-Intestinal Tract Ultrasound & Diagnostic as well Therapeutic Interventional Sonography. He is the Pioneer of Gastro-Intestinal Tract Sonography, especially Gastro-Duodenal Sonography. He has delivered many Guest Lectures in Indian as well International Conferences in nearly 27 countries as an Invited Guest Faculty, since March 2000. He is a Consultant Radiologist & the Specialist in Conventional as well Unconventional Gastro-Intestinal Tract Ultrasound & Diagnostic as well Therapeutic Interventional Sonologist in Pune, India
Abstract:
TransAbdominal Sonography of the Gall Bladder can reveal Hepatic & ExtraHepatic & Peritoneal Perforations of the Gall Bladder, whether it is impending perforations, frank perforations, sealed perforations, concealed perforations & its complications. It can also demonstrate adhesions in the Gall Bladder Fossa at the Right Upper Quadrant. All these cases are compared & proved with gold standards like Laparoscopic & Open surgery & endoscopy.
Some extra efforts taken during all routine or emergent ultrasonography examinations can be an effective non-invasive method to diagnose primarily hitherto unsuspected Gall Bladder impending perforations, frank perforations, sealed perforations, concealed perforations & its complications, so should be the investigation of choice.
- Liver and Biliary
Location: Hyatt Regency Osaka
Session Introduction
Omer Engin
Associate Professor of General Surgery. Health Sciences University, Tepecik Training and Research Hospital, Surgery Department, Izmir, Turkey
Title: Management of liver trauma: Case reports and literature review
Biography:
Omer Engin MD,
Associate Professor of General Surgery. Health Sciences University, Tepecik Training and Research Hospital, Surgery Department, Izmir, Turkey
Abstract:
A lot of surgeons may not do liver resection for malignancy in their surgical practice but they may have to operate liver because of traumatic injuries of liver. Such operations can be changed from simple suturing to resection. So, all of the surgeons must know liver anatomy and surgical operation techniques.
Liver injuries may occur after blunt or penetrating injuries. Clinical presentation may change from silent symptoms to shock symptoms. There are two liver injuries cases are presented except for another all of our liver injuries cases.
Some imaging modalities can be used that ultrasonography, CT, MRI as a noninvasive. Diagnostic peritoneal lavage and laparoscopy can be chosen such as invasive techniques.
Treatment of this lacerations can be divided into medical and surgical. Parenteral replacement of liquid, erythrocyte, thrombocyte and fresh frozen plasma are in the medical treatment options of the liver lacerations. Surgical management of the liver varies from patient to patient.
Abdel Rahman A Al Manasra
Jordan University of Science and Technology, Jordan
Title: Associate Professor of General Surgery. Health Sciences University, Tepecik Training and Research Hospital, Surgery Department, Izmir, Turkey
Biography:
Jordan University of Science and Technology, Jordan
Abstract:
Introduction & Aim: Fungal organisms can be found in biliary cultures of patients on prolonged antibiotics treatment and have stents; however, fungal masses, or balls, are rarely encountered and extremely difficult to eradicate. The aim of this study is to share our experience in fungal cholangitis complicating malignant bile duct obstruction and to reviews reports previously published concerning management of the recurrent obstruction secondary to Candida infections and its correlation with biliary malignancies.
Methods: We present our experience with 3 patients who complained of obstructive jaundice. All patients had multiple episodes of fungal cholangitis. Bile samples were obtained during percutaneous trans-hepatic cholangiogram (PTC). Two patients were diagnosed with cholangiocarcinoma and one with adenocarcinoma of the head of the pancreas.
Results: Persistent biliary candidiasis may carry a higher morbidity when it rises on the background of biliary malignancy, due to the prolonged course of medical treatment and patient hospitalization, recurrent obstruction with fungus balls, frequent needs to intervene with invasive procedures such as ERCP and PTC and the delay in initiation of chemotherapy.
Conclusion: Patients with positive fungal cultures of bile samples obtained by PTC may have coincidental cancers; similar to cholangiocarcinoma, peri-ampullary tumors and gallbladder cancer, therefore, screening with tumor markers, cytology samples and imaging studies is recommended. Aggressive sensitivity-based treatment with systemic antifungals along with external biliary drainage and irrigation with anti-fungals may be necessary for eradication of infection.
- Liver Diseases
Session Introduction
Jong Won Kim
Chonbuk National University, South Korea
Title: Inhibition of glutathione peroxidase-4 alleviates non-alcoholic steatohepatitis by suppressing lipid peroxidation in mice
Biography:
Jong-Won Kim is a Ph, D at the Chonbuk National University where he researches pathogenesis of several non-infectious diseases including acute or chronic hepatitis. He holds a B.S. degree in molecular biology and a Doctor of Veterinary pathology from the same university. He has his expertise and tries to clarify the mechanism of non-infectious diseases and contributes to the development of new therapeutic strategies.
Abstract:
Reactive oxygen species (ROS) plays a key role in non-alcoholic steatohepatitis (NASH). Inactivation of glutathione peroxidase-4 (GPX4) induces ferroptosis, which is an iron dependent and lipid peroxidation-mediated non-apoptotic form of cell death. The aim of this study was to investigate the impact of GPX4 on the progression of NASH at an early stage. C57BL6/J mice were fed a methionine and choline-deficient (MCD) diet for 10 days to induce NASH. To determine the role of GPX4 on NASH progression, the inhibitor (RSL-3) and the activator (sodium selenite) of GPX4, the inhibitor of ferroptosis (Liproxstatin-1, Lip-1) and an iron chelator (deferoxamine mesylate salt, DFO) were used in current experiments. RSL-3 treatment showed decreased hepatic expression of GPX4, 12/15-lipoxygenase and apoptosis inducing factor, indicating that GPX4 plays, a key role in NASH-related lipid peroxidation and its-associated cell death. Consistently, serum biochemical analysis showed increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in MCD-fed mice with RSL-3 treatment. In line with these results, NASH-related hepatic steatosis, inflammation and apoptosis were also increased in MCD-fed mice with RSL-3 treatment. However, sodium selenite treatment showed an opposite and protective effect on NASH progression in MCD-fed mice. Administration of DFO showed significantly lowered NASH severity and abolished the harmful effects of RSL-3-mediated GPX4 inhibition in MCD-fed mice. Finally, Lip-1 treatment showed repressed hepatic lipid peroxidation and its associated cell death resulting in decreased NASH severity. Consistent with in vivo findings, similar results were observed in palmitic acid-induced in vitro NASH condition. Taken together, we conclude that ferroptosis might play a major role in development of NASH. These results suggest that modulation of iron-mediated ferroptotic cell death might pave the way for a new strategy in treating NASH.
Rays H Y Jiang
University of South Florida, USA
Title: Using single cell omics to decode liver heterogeneity in development and cancers
Biography:
Rays H Y Jiang takes on a pioneer role in establishing a viable research program of genomics in University of South Florida, USA. She has published in high profile journals such as Cell, Science, Nature Communications and Genome Research and secured diverse funding sources from NIH, NSF and Gates’ foundations.
Abstract:
The human liver is the largest internal organ that performs over 500 physiological functions. We used single cell omics to study thousands of primary hepatocytes from human donors with healthy and pathological livers. We also developed specialized computational methods to decode single hepatocyte spatial and temporal information in livers. Our single cell RNAseq analysis revealed enormous transcriptional and biochemical heterogeneity within a single donor liver. We discovered that the principle of essential configuration of maximally incompatible biochemical pathways governs complex liver physiology in the liver lobules. We also studied hepatocyte heterogeneity at single cell level in developmental and cancer livers of humans. Within a hepatocyte cellular carcinoma biopsy sample, there is a continuum of oncogenic transformation degree of hepatocytes, which mirrors the embryonic liver developmental process with the exception of erythropoiesis function. The majority of the tumor derived hepatocytes show properties similar to that of healthy donors, albeit with reduced primary liver functions. Importantly, we found a small group of liver cancer stem cell like progenitors, expressing arrays of embryonic markers such as SOX4, HMGA1 and CXCR1, indicating enhanced onco-genic proliferation potential. Our single cell omics study revealed important temporal and spatial heterogeneity related to liver functions and oncogenic-transformation in humans.
Zhuo Wang
Southern University of Science and Technology, China
Title: Stat3 tyrosine phosphorylation is critical for hepatocellular carcinoma proliferation, survival and angiogenesis in response to lipopolysaccharide
Biography:
Zhuo Wang is a well-qualified, highly skilled and motivated person with more than 8-year work experience in liver disease. She has completed her PhD degree from Hong Kong Polytechnic University in 2014 and currently she is working at Southern University of Science and Technology. Her research focuses on liver fibrosis and liver cancer recently these years.
Abstract:
Hepatocellular carcinoma (HCC) is a long-term sequence of chronic inflammatory liver injury and hepatic injury is associated with a defective intestinal barrier and increased hepatic exposure to bacterial products including lipopolysaccharide (LPS), which promotes hepatocarcinogenesis. Despite its clinical signiï¬cance, mediators responsible for the high risk of inflammation to develop HCC in the chronically injured liver remain to be clarified. Here, we report a novel mechanism by which LPS/signal transducer and activator of transcription 3 (STAT3) signaling promotes the angiogenesis in HCC both in vitro and in vivo. STAT3 activated by LPS increases the production of vascular endothelial growth factor (VEGF) by tumor cells, which in turn stimulates the migration and tubulogenesis of endothelial cells through STAT3 activation and hence promotes angiogenesis in HCC. Moreover, our data suggested that hypoxia-induced VEGF expression, which also contributes to angiogenesis in HCC, was in a STAT3-dependent pathway. Our findings not only provide a potential mechanism by which bacterial infection enhances HCC oncogenesis through promoting the angiogenesis in liver, but also suggest that targeting STAT3 might be an effective therapeutic strategy in HCC treatment considering the dual roles of STAT3 in angiogenesis.
Claudio Agustino
Faculty of Medicine University of Indonesia , Indonesia
Title: Comparison between Albumin, Prothrombin Time, and Fibrinogen Profile in Staging of Liver Cirrhosis based on APRI Score Classification
Biography:
Claudio A is a medical student from University Indonesia. He has won several competitions such as
Scientific Poster in Tarumanegara Medical Competition held by Tarumanegara University and
emergency medical responder held by the National Medical First Responder Team Organization.
He also active in several organization such as First Responder Team in Faculty of Medicine
University of Indonesia and Student Council Organization. As a medical student, he also made a
research and wrote Evidence Based Case Report about Hepatology and interested in that field.
Abstract:
Cirrhosis is an end stage of chronic inflammatory disease with the destruction of liver tissue and
fibrosis that impairs its function to synthesis albumin, prothrombin, and fibrinogen. Cirrhosis can be
detected and classified into 3 groups with non-invasive diagnostic technique by using APRI score.
This study aims to find out the significant difference between albumin, prothrombin time, and
fibrinogen profile within cirrhosis stages based on classification from APRI score. Design of the
study is cross sectional with 60 patients which meet the criteria from the medical records in the
Clinical Pathology Laboratory and center of medical record of RSCM.: The results of the study
were analyzed with Kolmogorov Smirnov test showed albumin level, prothrombin time, and
fibrinogen (median 2.91, 11.8, and mean 273.7117) , Anova or Kruskal Wallis test showed
significant difference between these three components based on score APRI classification. ( all
p<0.05).Then, Post hoc test (Bonferroni for Anova, Mann Whitney for Kruskal Wallis) of
albumin’s profile showed significant difference for comparison between group APRI score less than
0.5 and more than 2. Post hoc test of prothrombin time showed significant difference from all
comparisons. Post hoc test of fibrinogen profile showed significant difference from comparison
between group APRI less than 0.5 and more than 2 ; APRI less 0.5 – 2 and more than 2. As a
results, there are significant difference from comparison between albumin, prothrombin time, and
fibrinogen profile in staging of liver cirrhosis based on classification from APRI score.