Day 1 :
Temple University, USA
Time : 09:20-09:50
Mark Feitelson attended Cypress College (Cypress, CA) from 1970-72, and then received a BS degree in Biology from the University of California, Irvine in 1974. Advanced studies resulted in a PhD in Microbiology and Immunology from the UCLA School of Medicine in 1979. His thesis presented the genetic organization of the rabbit papilloma virus. He was then an American Cancer Society Postdoctoral fellow in the Department of Medicine at Stanford University from 1980-1982, where he started his work with hepatitis B virus (HBV). He was then recruited to the Fox Chase Cancer Center by Dr. Baruch Blumberg (who won the Nobel Prize for his discovery of HBV) where he continued his work in HBV. He is presently Professor of Biology at Temple University and Associate Director of the Temple Biotechnology Center. He has been consistently funded by NIH and foundations since 1988 for basic science work on HBV and has attracted 10 contracts from industry for translational and applied work since 1997. He has over 100 publications in highly ranked international scientific journals, has written two books; delivered more than 160 oral presentations and/or posters at national and international scientific meetings, and has delivered more than 100 invited lectureships all over the world.
Hepatitis B virus (HBV) is a major etiologic agent of chronic liver disease (CLD) and hepatocellular carcinoma (HCC). HBV encoded X antigen, HBx, and pathways implicated in the self-renewal of stem cells contribute to HCC, but it is not clear whether HBx expression promotes “stemness”. Thus, experiments were designed to test the hypothesis that HBx triggers malignant transformation by promoting properties that are characteristic of cancer stem cells (CSCs). To test this hypothesis, HepG2 cells were stably transduced with HBx and then assayed for phenotypic and molecular characteristics of “stemness”. The relationship between HBx and “stemness”-associated markers was also evaluated by immunohistochemical staining of liver and tumor tissue sections from HBV infected patients. The results showed that Oct-4, Nanog, Klf4, β-catenin and EpCAM were activated by HBx in vitro and in vivo. EpCAM was detected in the nuclei of human HCC cells from infected patients. HBx promotes “stemness” by activating β-catenin and epigenetic up-regulation of miR-181, both of which target EpCAM. HBx expression was also associated with depressed levels of E-cadherin. Moreover, HBx stimulated cell migration, growth in soft agar, and spheroid formation. This work is the first to propose that HBV promotes “stemness” in the pathogenesis of HCC. HBx associated up-regulated expression of multiple “stemness” markers support the hypothesis that HBx contributes to hepatocarcinogenesis, at least in part, by promoting changes in gene expression that are characteristics of CSCs.
Time : 09:50-10:20
Trent W. Nichols Jr. MD, is an internist, nutritionist, and gastroenterologist with more than 30 years of clinical experience. He is the founder and director of the CNDD and the Advanced Magnetic Research Institute in Hanover, Pennsylvania. He is a graduate of the University of Denver with a BS in Chemistry and Northwestern University with a MD. His postgraduate education medicine was at Northwestern University in Internal Medicine and Fellowship in Gastroenterology and Hepatology. He has been the lead investigator in over 50 pharmaceutical trials and has worked for the Veterans Administration, Kaiser Permanente, Good Samaritan Hospital in Lebanon PA, and Sinai Hospital In Baltimore MD. He is a member of the American Gastroenterology Association, Society for Neuroscience, and Bioelectromagnetic Society. He is on the editorial panel of the Journal of Liver OMICS and has been active researcher in the role of mitochondrial dysfunction in liver disease and therapy with EMF.
At DDW 2014, S Mittal showed that over 1500 Veterans in 2013 were diagnosed with HCC and that this trend is increasing every year. The greater percentage of patients with NAFLD- related HCC did not undergo HCC surveillance (Clinical Gastroenterology and Hepatology 2014). The VA now has 10 times more patients diagnosed with hepatocellular carcinoma (HCC) than it did a decade. “Unless we do something dramatic, 10,000 Vietnam veterans will die of liver cancer in the next five years.” stated Douglas Heuman MD, Chief of Hepatology and Medical Director of Liver Transplantation at VA Medical Center Richmond and Professor of Medicine at Virginia Commonwealth University. Vietnam veterans have the greatest risk of HCC because they have the highest hepatitis C virus infection and other comorbid factors, smoking, alcohol abuse, obesity, diabetes, metabolic syndrome associated with insulin resistance and their association to (NASH) non- alcoholic steatohepatitis and the progression to cirrhosis (US Medicine 2014). Last year at VISN6 Mid-Atlantic, 221 hepatitis C patients, and 55 NASH/NAFLD were treated at Martinsburg VHA and ~500 at VAH Baltimore and DC combined. The huge economic burden of Hep C therapy will be discussed and the need to combine Ledispravir/ Sofosbuvir or Viekara with Ribavirin for cirrhosis for truncated therapy. High dose vitamin D3 in a weekly oral dose of 50,000 U was used at VHA Martinsburg in patients with HCV while undergoing Sof/Sim oral therapy and later Harvoni or Viekara to prevent HCC as well as those with NASH, NAFLD and alcohol dependence. A previous epidemiology study by Fedirko Hepatology 2014 demonstrated the risk of HCC was reduced by 49% in those Europeans with the highest levels of 25(OH)D. NASH/NAFLD patients and HBV patients on Entecovir were also given Cholecalciferol. The fact that fatty Liver/NASH patients present challenges in diagnosis, therapy and HCC surveillance will also be discussed, as well as the large global hepatitis B problem with 1 billion potential patients and the potential for CRISPR scissors antiviral therapy. Liver transplantation alone at 1/10 patients currently on the transplant list in the USA with cirrhosis currently is insufficient and future novel solutions are suggested.
Chang Gung Memorial Hospital, Taiwan
Time : 10:20-10:50
Sen-Yung Hsieh has completed his MD from National Yang Ming University, Taipei, Taiwan, and PhD from University of Pennsylvania, PA, USA. He completed his clinical training in gastroenterology and hepatology at Chang Gung Memorial Hospital, Taiwan. Currently, he is the Director of the Department of Medical Research and Development, Director of the Clnical Proteomics Center, and Professor of Gastroenterology and Hepatology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan. He has published many papers in reputed journals including Hepatology, J Hepatology, Mol Cell Proteomics, Oncogene, Nucleic Acid Res, and Proc Natl Acad Sci, USA, and has been serving as an Editorial Board Member of many reputed journals.
It has been a long-term enigma why Hepatocellular Carcinoma (HCC) runs a relatively lower rate of systemic metastasis and metastatic cancer which is rarely seen in the liver with cirrhosis. Most HCC occurs in cirrhotic livers, which are characterized by thrombocytopenia. Platelets contain not only hemostatic factors but also tremendous kinds of factors including bioactive metabolites (throboxane A2, adenosine, serotonin, thrombin), cytokines/chemokines (TGF-1, IL-1, CCL5, IL-8), and growth factors (PDGFs, HGF, EGF, IGF-1, VEGF) playing crucial roles in hemostasis, wound healing and tissue regeneration. On the other hand, platelets may also exert harmful effects by facilitating inflammation and tumor progression. In this presentation, the impact of platelets, particularly cirrhosis and thrombocytopenia, on the prognosis of HCC will be discussed.