Day 1 :
Keynote Forum
Dr. Mark A Feitelson
Temple University, USA
Keynote: Does hepatitis B antigen HBx promote the appearance of liver cancer stem cells?
Time : 09:20-09:50
Biography:
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.
Abstract:
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.
Keynote Forum
Trent W Nichols
AMRI, USA
Keynote: The growing epidemic in HCC from hepatitis/NASH cirrhosis in American veterans
Time : 09:50-10:20
Biography:
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.
Abstract:
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.
Keynote Forum
Dr. Sen-Yung Hsieh
Chang Gung Memorial Hospital, Taiwan
Keynote: Impacts of platelets on the prognosis of patients with hepatocellular carcinoma
Time : 10:20-10:50
Biography:
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.
Abstract:
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-ï¢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.
- Symposium
Location: Prestwick
Session Introduction
Dr. Andre Jean Remy
Perpignan Hospital, France
Title: New Tools Of Screening Viral Hepatitis In Real Life: The French Model Of Care
Time : 11:30-12:30
Biography:
André-Jean Remy, is Head of Hepatology and Gastroenterology Unit & of Social Medicine Unit of Perpignan Hospital. He is the Medical coordinator of Mobil Hepatitis Team, General Secretary of ANGH. He is an Administrator of AFEF (French Liver Diseases Association) and a specialist of viral hepatitis in drug users, inmates and precarious populations. He has published more than 150 scientific articles.
Abstract:
Introduction: Hepatitis B and C screening was usually done by serology in laboratories or medical centers. If serology was positive, viral load was determined and after that patient saw hepatologist. Liver fibrosis was measured after first medical consultation. All steps took 3 months. Methods: So hepatitis mobile team proposed new model of screening high risk patients for hepatitis C or B. Nurse and social worker came together in outreach centers, jailhouses, drug services centers and all structures which care drugs users, homeless and precarious patients. They offer triple screening in same time: 1/ social screening with specific score called EPICES, 2/ POCT for HCV HBV 3/ liver fibrosis screening by FIBROSCAN*. With these results, patient could do his/her biology quickly and see hepatologist in 2 weeks only. Drug injection was main contamination route of hepatitis C virus (HCV) in France and Western Europe since 1990. Results: 711 POCT were done in 12 months: 19 positive for new patients and 69 positive for already known patients who returned to medical care; 7 POCT were positive for HBV (but only for 6 months); 393 FIBROSCAN* were done (medium rate 7.8 KPa, fibrosis level F2), 68% for HCV, 3% for HBV and 29% for alcoholic liver disease. Social screening showed that 91% of our patients were precarious. 134 patients were addressed to on site hepatologist consultations. 45% of patients were treated and only 3% lost sight. Conclusions: Our model of care, based on site screening and follow up, increased number of patients diagnosed, treated and cured.
- Liver Cancer and Hepatocellular Carcinoma
Advanced Management of Liver Diseases
Clinical Liver Transplantation and Liver Surgery
Location: Main Hall 1
Chair
Dr. Mark A Feitelson
Temple University, USA
Co-Chair
Dr. Francisco Antonio Bezerra Coutinho
School of Medicine University of Sao Paulo, Brazil
Session Introduction
Dr. Maxwell M Chait
Columbia University College of Physicians and Surgeons, USA
Title: Advances in Hepatology
Time : 12:55-13:20
Biography:
Maxwell M Chait completed his MD degree at the age of 25 from the University of California School of Medicine at San Francisco. He is a Fellow of several prestigious organizations, including the American College of Physicians, American College of Gastroenterology, American Gastroenterological Association and the American Society for Gastrointestinal Endoscopy. He is a practicing gastroenterologist on the faculty of the Columbia University College of Physicians and Surgeons. He has authored numerous publications and serves on the editorial board of the World Journal of Gastrointestinal Endoscopy and the Journal of Liver Disease and Transplantation Biology.
Abstract:
The field of hepatology has had major advances in the evaluation and management of liver disease. The burden of liver disease worldwide depends on essentially on the incidence of cirrhosis and hepatocellular carcinoma. The major factors causing cirrhosis are alcoholic liver disease (ALD), hepatitis B and C and nonalcoholic liver disease (NAFLD). Effective therapies for hepatitis B and C have been developed that continue to evolve with remarkable success. ALD remains a major health problem and NAFLD has become a health problem of epidemic proportions. Abstinence from alcohol and reduction in obesity are the major preventative strategies for theses illnesses. Approaches continue to be developed to manage the complications of cirrhosis and hepatocellular carcinoma. Liver transplantation has evolved to a standard therapy for end-stage liver disease. Reducing the burden of liver disease through prevention, cure and treatment of complications is now possible.
Biography:
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.
Abstract:
Background: 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. Additionally, a previous report by L Bi has shown that WNT5a has been shown to be involved in cancer progression and was down-regulated in hepatocellular cancer. We have previously reported that many genes in obesity and fatty liver (NAFLD) are associated with insulin resistance and their association to Non-Alcoholic Steatohepatitis (NASH) and the progression to cirrhosis. We now report that many of these genes seen in NASH are regulated by static magnetic fields and that WNT5a is up-regulated. Methodology: Gene array analysis of 2 human embryonic stem cells lines in another experiment of 0.23-0.28 T Static Magnetic Fields (SMF) at JHU, as previously described, was conducted to exam the mechanism of DC EMF via the impact of altered Ca2+ flux and lipid membrane domain fluidity on signaling pathways via TRL4 and IL6. Some 2500 genes were found to be up and down-regulated. Recently, further inspection was conducted on Cell Cycle, Cancer, Cell to Cell Signaling, and Cellular Development. Results: Analysis of ingenuity pathways of the Affymetrix gene arrays revealed WNT5a up-regulation by SMF after down-regulation of IL6 mRNA at 5 days in stem cell lines. Down-regulation of tumor necrosis factor alpha and up-regulation of TLR 4 were demonstrated for this transformation. Chemokine genes CCL2, CXCl1, CXCL2, MMP9, SERPINE1, IL6, and IL1B (genes for fibrosis) were down-regulated. TIMP1 and SOCS3 metalloproteinase inhibitors were up-regulated. Forkhead FOXO1 and 3 transcription factors were also up-regulated at 5 days. FOXM1 expression when silenced has been found to suppress human HCC cell growth in vitro by Park. Of the 47 genes up-regulated in NASH in obesity and NASH, 11 were identified as down-regulated by SMF and 2 up-regulated which can prevent fibrosis. Discussion: WNT5a up-regulation by SMF leads to NLK down regulation. Nemo Like Kinase -SETDB1 complex subsequently interacts with PPARG. Methylation of PPARG target promotes histone H3KP and transcriptional silencing inhibiting adipogenesis. Conclusions: Polygene up-regulation and down-regulation occurs in fatty liver/NASH. Moderate magnetic field therapy was found in 1 week of therapy of an animal model to reduce fat in Ob/Ob mice by this author and in human stem cells lines suggesting that such therapy may be helpful in therapy for NASH to prevent HCC. Adding electrons to the mitochondria electron transport chain is one of the suggested mechanisms. Accelerated liver detoxification by moderate magnetic therapy of obesogens in human subjects that disrupt homeostasis of metabolism of lipids ultimately resulting in obesity is also possible. Activation of AMPK inhibits cancer cell growth through AKT/FOXO3a/FOXM1 signaling cascade. Polygenic up and down-regulation in NASH and its progression to HCC via DC EMF is, therefore, a possible solution to this epidemic problem. High dose Vitamin D3 in a weekly oral dose of 50,000 U was used at VHA Martinsburg in 221 patients with HCV while undergoing Sof/Sim oral therapy and later Harvoni or Viekara to prevent HCC. A previous epidemiology study demonstrated that 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.
Dr. Mark A Feitelson
Temple University, USA
Title: Hedgehog Signaling Blockade Delays Hepatocarcinogenesis Induced by Hepatitis B Virus X Protein
Time : 13:20-13:45
Biography:
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.
Abstract:
The hepatitis B virus (HBV) encoded X protein (HBx) contributes centrally to the pathogenesis of hepatocellular carcinoma (HCC). Aberrant activation of the Hedgehog (Hh) pathway has been linked to many tumor types including HCC. Thus, experiments were designed to test the hypothesis that HBx promotes HCC via activation of Hh signaling. HBx expression correlated with an upregulation of Hh markers in human liver cancer cell lines, in liver samples from HBV infected patients with HCC, and in the livers of HBx transgenic mice (HBxTg) that develop hepatitis, steatosis, and dysplasia, culminating in the appearance of HCC. The findings in human samples provide clinical validation for the in vitro results and those in the HBxTg. Blockade of Hh signaling inhibited HBx stimulation of cell migration, anchorage-independent growth, tumor development in HBxTg, and xenograft growth in nude mice. Results suggest that the ability of HBx to promote cancer is at least partially dependent upon the activation of the Hh pathway. This study provides biologic evidence for the role of Hh signaling in the pathogenesis of HBV-mediated HCC and suggests cause and effect for the first time. The observation that inhibition of Hh signaling partially blocked the ability of HBx to promote growth and migration in vitro and tumorigenesis in two animal models implies that Hh signaling may represent an "oncogene addiction" pathway for HBV-associated HCC. This work could be central to designing specific treatments that target early development and progression of HBx-mediated HCC.
Dr. Mamdooh Ghoneum
Charles Drew University of Medicine and Science, USA
Title: Effect of arabinoxylan rice bran (Biobran) on viremia level in patients with chronic HCV infection
Time : 10:00-10:25
Biography:
Ghoneum M obtained his PhD from the University of Tokyo, Japan, and completed Postdoctoral research at the University of California, Los Angeles. He is the Director of Research in the Department of Otolaryngology at Charles R. Drew University of Medicine and Science, Los Angeles, CA. He has published more than 100 papers in reputed journals and has been serving as an Editorial Board Member of repute. For the last two decades, he has been focused on the discovery of natural anti-viral, anti-cancer agents.
Abstract:
Hepatitis C virus (HCV) has infected approximately 12 million people in Egypt with 40,000 deaths/year. Current treatments for HCV using synthetic antivirals have severe side-effects. Therefore, there is a need to explore the therapeutic applications of natural products. We examined the anti-HCV effect of Biobran, an arabinoxylan from rice bran, on viremia in patients with chronic HCV. Patients with positive HCV (N=39) were randomized into two groups. One group served as a control, receiving standard treatment of PEG Interferon plus Ribavirin (N=22), and the second group was treated with Biobran (1 g/day) (N=17). The level of viral load was examined before and 3-months after treatment. The group treated with Biobran and the group treated with Interferon both showed a significant reduction in the viral load after 3 months of treatment relative to the baseline viral load (p<0.05). The reductions in the viral load of the two groups were comparable (p>0.05). However, the Biobran group demonstrated no side effects and patients reported good health, while among the control group there was fever, anaemia and thrombocytopenia, and the patients reported easy fatigue. We conclude that Biobran is a novel therapeutic regimen that is safe and effective in the treatment of chronic HCV. The mechanisms by which Biobran exerts its effect may involve activation of human immune cells that are known to exhibit antiviral activity. Ongoing studies are designed to examine the long-term effect of Biobran on the treatment and the recurrence of HCV in multiple clinical trials.
Dr. Sen-Yung Hsieh
Chang Gung Memorial Hospital, Taiwan
Title: Functional Genomics Identified A Novel Cell-Cell Contact Inhibition Mechanism involved in Hepatocarcinogenesis
Time : 14:30-14:55
Biography:
Sen-Yung Hsieh earned his MD degree from the National Yang Ming University in 1983, and obtained his PhD in Molecular Virology and Pathology from University of Pennsylvania in 1991. He received his clinical training in internal medicine, and subsequent a specialty in hepatogastroenterology in Chang Gung Memorial Hospital, Linko, Taiwan. He initially focused on the molecular virology and epidemiology of human hepatitis viruses. His team for the first time identified the zoonotic transmission of hepatitis E virus from swine to humans in 1998, which was later found in other wild and domestic animals as natural reservoirs for sporadic hepatitis E in Japan, western countries, and other parts of the world. Currently, he is interested in elucidation the molecular mechanisms involving in carcinogenesis of human hepatoma. By integration of both functional genomics and molecular and cellular biology, he has identified novel oncogenes, tumor suppressor genes, and pathways that play significant roles in oncogenesis of human hepatoma. His works have been published in J Virology, Nucleic Acid Res, PNAS, Cancer Research, Oncogene, Proteomics, J Proteome Res, Mol Cell Proteomics, J Hepatology, and Hepatology. His main research field is Hepatocellular carcinoma: Carcinogenesis mechanisms, diagnosis, and treatments.
Abstract:
It is unclear how proliferating cells elicit suppression on cell proliferation and how cancer cells evade this growth suppression. Using a loss-of-function screening of the human kinome and phosphatome to identify genes suppressing tumor initiation in human hepatocellular carcinoma (HCC), we identified 19 genes and characterised one of the top scoring tumor suppressor candidate, Protein Tyrosine Phosphatase Receptor type F (PTPRF). We found that PTPRF was induced during cell proliferation by cell-cell contact. Ectopic expression of wild-type PTPRF, but not the phosphatase-inactive mutant, suppressed cell proliferation and colony formation in soft-agar assays. In contrast, PTPRF silencing led to cell hyperproliferation, enhanced tumor colony formation in soft-agar, and increased xenograft tumor growth in nude mice. Mechanistically, PTPRF silencing showed aberrant ERK-dependent signaling including the phosphorylation/stabilization of MYC through the direct activation of SRC and suppression of PP2A. This PTPRF-mediated growth suppression during cell proliferation functioned independently of the Hippo-Yap pathway. Clinically, PTPRF was downregulated in 42% HCC (37/89), 67% gastric cancer (27/40), and 100% colorectal cancer (40/40). PTPRF upregulation was found in 24% HCC (21/89) and associated with better clinical outcomes. Conclusion: A novel PTPRF-mediated growth suppression pathway was identified via a functional genomics screening in human hepatoma cells. Induction of PTPRF by cell-cell contact during cell proliferation quenched the activated ERK-dependent proliferation signaling to prevent cell hyperproliferation and tumor initiation. PTPRF downregulation in HCC facilitated tumor development. Our findings have shed light on how cancer cells can evade growth suppression and open a new avenue for future development of anticancer therapies.
Dr. Francisco Antonio Bezerra Coutinho
School of Medicine University of Sao Paulo, Brazil
Title: Modeling and Restoring a defective data base on Hepatitis C
Time : 10:25-10:50
Biography:
Francisco Antonio Bezerra Coutinho completed his PhD at the University of Sussex (UK) in 1972. He did Postdoctoral Studies at the same university and also at McMaster University, Ontario, Canada. He published about 140 papers in pair reviewed journals but a large fraction of these are in Mathematical Physics. He was associated Editor of the Brazilian Journal of Physics and is Associated Editor of Frontiers of Physics.
Abstract:
Notification of cases of hepatitis C is compulsory in Brazil. So the Brazilian Ministry of Health has a large Data Base with the number of notified cases (per year) of hepatitis C, with the age and sex of the patients each year since 2004. This database is called SINAN. This data lists the cases from all the states of Brazil separately. From SINAN we can calculate the reported incidence of hepatitis C and also its prevalence. The problem is that the notification process is not perfect so the data base underestimates the prevalence of Hepatitis C in the country. It is possible however, to model the reasons for the lack of notification and therefore to estimate the real prevalence of hepatitis in Brazil of even for each state of the federation. There are many ways of doing this. In this work, we present only two ways of calculating the prevalence of Hepatitis from the defective reported incidence. The result can be used to design a statistical survey of hepatitis C. Comparing the result of the survey with the result of the model the notification process can be improved.
Dr. Faustino Bisaccia
University of Basilicata, Italy
Title: New insight on the hepatite B x antigen effector URG7
Time : 11:20-11:45
Biography:
Faustino Bisaccia completed his Degree in Chemistry and Pharmaceutical Technology in 1982. Currently he is a Director in the Department of Science at the University of Basilicata.
Abstract:
The up-regulated gene clone 7 (URG7) encodes a 99 amino acids protein induced by the hepatitis B virus antigen x (HBxAg). The first 74 amino acid residues are identical to the N-terminal residues of the multidrug-resistance protein 6 (MRP6). Studies carried out on cells transfected with HBxAg or URG7 have demonstrated that URG7 is able to prevent the TNFα- induced apoptosis by inhibiting the caspase 3 and 8 and activating the phosphoinositide 3-kinase and the beta-catenin pathways, thus favoring the survival of the infected cells. Anti-URG7 antibodies, found in the serum of HBV carriers, are considered pre-neoplastic markers for hepatocellular carcinoma (HCC). Recent studies have shown that the URG7 protein is glycosylated at the N-terminal region and is localized in the endoplasmic reticulum (ER) with the N-terminus in the ER lumen and the C-terminal in the cytoplasm. As HBV infection causes ER stress promoting the accumulation of unfolded protein aggregates, we investigated the role of the URG7 protein in the ER stress. Obtained results show that HepG2 cells over-expressing URG7 treated with tunicamycin show a specific pattern of ER stress markers expression suggesting that URG7 drives cells toward survival rather than apoptosis. This result suggests that URG7 can be a molecular target to promote apoptosis in HBV- infected cells.
Dr. Mayson Abu Raya
Rappaport Faculty of Medicine, Technion, Israel
Title: Histomorphometric findings may help predict response to antiviral therapy at an early fibrosis grade in patients with chronic HCV infection
Time : 16:25-16:50
Biography:
Maison Abu Raya has completed her MD (cum laude) and graduated at the age of 26 from the Technion Institute of Technology, Rappaport Faculty of medicine, Haifa, Israel, one of the prestigious medicine school in Israel.
Abstract:
Introduction: HCV is a leading cause of cirrhosis and hepatocellular carcinoma and is the leading indication for liver transplantation in the United States. In the United States, genotype 1 is the most predominant, especially in HIV-HCV co-infected and the African-American population.Several viral and host factors related to viral response have been reported. Histomorphometry is a quantitative method for investigating changes in shape, size and orientation of cells in tissues. Morphometry has been used in various fields, to predict disease phenotype and patients prognosis. Aim: To use computerized histomorophometry in order to quantify the histological changes that occur in liver biopsies obtained from patients with chronic HCV, in the purpose of predicting the response to medical treatment in these patients. Methods: Patients with chronic HCV genotype 1, with Metavir score F1 and F2 followed at our liver unit have been selected and grouped according to treatment response {SVR (sustained viral response) and non-SVR} into 30 patients per group. Histolomorphometric analysis has been blinded to patient identification or previous histological information. Histological slides from the pretreated liver biopsies were scanned using the dot slide virtual microscopy (Olympus) system. 3-4 representative images were captured per slide. Each liver biopsy contained 6-8 representative portal spaces in average. The ImagePro plus 7.0 (Mediacybernetics USA) program has been used to quantify the amount of collagen fibers, the number of inflammatory cells and textural changes of the livers parenchyma. The Matlab software (Mathworks, USA) was used to calculate fractal and lacunar dimensions of the liver parenchyma in order to capture any structural changes in the livers general architecture. Results: Histomorphometric variables including the density of collagen fibers, the fraction of inflammatory cells per portal space area, and textural parameters were found to bestatistically significant and could be combined together in a mathematical formula, in order to predict response to treatment in HCV patients, with sensitivity of 93%, and 100% specificity. Conclusions: Our study indicates that computerized histomorphometry can be used to quantify the level of fibrosis, amount of inflammation, and the changes in the parenchymal texture and complexity in chronic HCV patients. Histomorphomertic method is promising and may contribute to developing a novel expert guided automatic system predicting response to treatment in chronic HCV patients, already at an early stage when histological changes are minimal, which may affect choosing suitable treatment for each patient. Morphometry may be used in the future to investigate liver diseases due to different etiologies.
Mr. Hakim Bouchkira
Hospital of Perpignan, France
Title: Hepatitis mobile team: A new concept for benefit toward drugs users with hepatitis C
Time : 12:00-12:25
Biography:
Mr. Hakim Bouchkira is Nurse Coordinator of Mobile Hepatitis Team. He is working in Perpignan Hospital since 2006.
Abstract:
Introduction: 44% of French drugs users were positive. Treatment of hepatitis C changed in 2011 with use of first antiviral direct agents. It was more difficult with tritherapy than dual therapy for drugs users to access to hepatitis screening, care and treatment. All these patients need support especially psycho-educative interventions. Methods: To improve this situation, we created in July 2013 the first hepatitis mobile team (HMT) composed of hepatologist, 2 nurses, social worker and secretary. There were 6 goals for HMT: Screening of hepatitis C with point of care testing, screening of liver fibrosis with portable FIBROSCAN, social screening, hepatology consultation directly in each partner unit, psycho-educative interventions and formation of social and medical staffs. All these actions were realized outside of hospital. One referent was first choosing in each drug user care unit and also in jail house medical unit. HMT became quickly helping unit to support hepatitis C patients, especially for drug users, inmates, homeless, psychiatric patients, emigrants or patients without social insurance. HMT action completed other medical and social actions in difficult social area. We also used an original psycho-educative intervention program created in 2009 with specially-trained nurses outside of our hospital. Program was available for out-of-treatment patients and was free and optional for patients. Patients could call nurse 7/7 days; 325 patients were included in 5 years. Results: At 31st August 2014, 22 different units in Perpinya area (500 000 people) were partners of HMT : Low and high threshold methadone units, retention and detention center medical units, free meal programs, outside psychiatric units, emergency and medical hosting units. After 12 months of activity, HMT organized 5 weekly hepatology consultations, 15 weekly or monthly nurse consultation; we took care of 399 patients; 240 FIBROSCAN and 283 HCV quick tests were realized ; 4% of quick tests were positive; 44 patients known as HCV positive came back to medical care; 12% of patients had cirrhosis or severe liver fibrosis; hepatologist saw 77 different patients and 51 patients began treatment with individual psycho-educative interventions; 16 collective psycho-educative interventions were also realized for total of 76 patients. Conclusions: HMT was new concept of hepatitis C care outside of hospital and doctor’s practice. It permitted screening, liver evaluation, care and treatment of difficult HCV patients in specific medical or social care units, which was usual and comfortable for patients. Our highlights were to be easy link between outside structures and hospital (date of appointment, orientation hospital partners), extension of screening outside of hospital, which complements existing screening offer, in proximity to places where live precarious patients and drug users, to cover whether geographical or social white areas, reactivity of supported when the 1st call (FIBROSCAN within 48h), rapid specialist consultation (within 72 hours) and orientation to active dynamic patient care. HMT was an innovative concept that promotes return of known HCV patients in circuit of care by facilitating access to FIBROSCAN then specialist consultation. With invested teams and adherence to the project; we could increase number of HCV precarious patients and/or drug users supported, treated and cured. French experts report said in May 2014 1/Treat all patients with mild and severe liver fibrosis F2 F3 F4 and 2/Treat all drugs users and inmates even if no liver fibrosis. That was our daily actions since HMT beginning.