Day 1 :
Keynote Forum
David H Van Thiel
Advanced Liver and Gastrointestinal Disease Centre, USA
Keynote: Endocan a valuable biomarker for hepatocellular carcinoma (HCC)
Time : TBD
Biography:
David H Van Thiel obtained his MD from the University of California at Los Angeles and completed Internal Medicine residencies at Cornell University Hospitals and Boston University. He completed a Gastrointestinal/Hepatology fellowship at Boston University and the University of Pittsburgh. At the latter institution, he progressed from an Instructor of Medicine to Professor of Medicine and Director of the Gastroenterology Hepatology Program and served as the medical Director of Liver transplantation. He has published more than 100 peer reviewed papers in a variety of journals and is on the Editorial Board of several journals as well as serves as a Reviewer.
Abstract:
Hepatocellular carcinoma (HCC) occurs at the rate of more than 500,000 cases and is the 6th most common cause of cancer worldwide. It is also the 3rd leading cause of cancer related death. Currently, increasing number of cases of hepatocellular carcinoma are being referred for liver transplantation as a result of changes in the MELD score points awarded to such individuals. A host of laboratory and imaging studies are utilized currently to detect in the resected hepatic tissue, tumor size within the resected specimen, and the presence of satellite nodules as well as the presence of additional foci of tumor and an alpha-fetoprotein level greater than 750 post intervention have been utilized to address this latter issue. The major problem with these analysis is that they can only be addressed after the intervention has ocurred. What is needed is a biomarker that can be utilized prior to either a non surgical or surgical intervention that identifies cases with a high likelihood of cure or alternatively a high likelihood of having a long-term survival that justifies the intervention. Endocan is a soluble proteoglycans of 50 kD that is over expressed by endothelial cells in several different carcinomas and is associated with a change in endothelial status from that of a dormant cell to one associated with fast-growing tumor and enhanced tumor progression. As such, endocan may be the useful marker for guiding clinicians at selecting the best therapy (radiofrequecy ablation, radioactive beads, chemoembolization, resection or transplantation) for individuals with HCC. Moreover, it would appear to be an important target for future immunotherapeutic approaches for the treatment of hepatocellular carcinoma by inhibiting endocan activity, thereby inhibiting tumor growth and progression (metastases).
Keynote Forum
Trent W Nichols
AMRI and CNDD, USA
Keynote: Wnt signaling in hepatocellular carcinoma, an emerging epidemic: Gene up regulation of Wnt 5a pathways with toll receptor 4 with moderated magnetic fields on human stem cells and mice and high dose vitamin D3 prevention
Time : TBD
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:
Liver cancer (HCC) is increasing in the USA and around the world. Although there is now effective therapy for Hepatitis C, fatty liver (NAFLD/NASH) has no recognized medical therapy other than weight loss. However, Metformin and PPAR gamma agonist have been associated with lower risk and improved prognosis of HCC. More than 95 % of patients with HCC have either upregulation in the signaling protein Wnt or its receptor Frizzled, or down–regulation of Frizzled receptors making the WntT/β-Catenin pathway a potential important therapeutic target according to an article in the Journal for Cancer Research. Current strategies for disrupting Wnt signaling include monoclonal antibodies against Wnt protein or the Frizzled receptor using soluble receptors for Frizzled to neutralize Wnt. Another approach is by using GPC3 a heparin sulfate proteoglycans that act as Wnt co-receptors of modulators. We will discuss the WNT/βCatenin pathway and then review the many genes (polygenetics) in obesity and fatty liver (NAFLD/ NASH) and the epigenetics of methylation involved in NASH and HCC. Additionally the mitochondrial defects seen in the metabolic syndrome will be discussed. Until recently, this hypothesis that has received little attention and that is the mitochondrial defects seen in metabolic syndromes or diabetes 2, fatty liver and insulin resistance. In our past experiments, moderate magnetic fields of 0.5T change 2, 500 gene expressions with dramatic changes in mouse morphology, liver fat and metabolism!. Genes involved in Wnt signaling were down regulated in NASH but have been up-regulated in HCC. Research of the author in mice and humans will be reviewed and gene array analysis of human embryonic stem cells in another experiment of 0.23-0.28 T static magnetic fields by Wang and Yarema collaborators at JHU will be discussed. Up-regulation of genes for insulin factors genes, peroxisome proliferative activity receptor were increased, and calcium channel gene and other genes for mitochondrial ribosomal protein S, and uncoupling protein 2. Down- regulation of tumor necrosis factor alpha and up- regulation of TLR 4 via Wnt signaling and interleukin 6 were demonstrated for this transformation. A methylated gene in obesity has recently been published by Su which is also affected. Mitochondrial dysfunction in obesity, fatty liver and NASH has previously been described. Forkhead transcription factors are also up-regulated at 5 days. Of the 47 genes up regulated in NASH by a study by Bertola. 13 were identified as down-regulated by SMF and 2 up-regulated. Genes for fibrosis are also down-regulated. The use of high dose vitamin D3 in prevention will be discussed starting with the European Prospective Investigation into Cancer and Nutrition publication and then the Vitamin D signaling pathways as potential for anticancer therapeutics with their potential as anticancer agents because their administration has antiproliferative effects, activation of apoptotic pathways and inhibition angiogenesis.
- Track 1: Hepatology
Track 2: Diagnosing Liver Diseases
Track 3: HBV and HCV Vaccines
Track 5: Viral and Non - viral Hepatitis
Session Introduction
Eve-Isabelle Pecheur
Cancer Research Center of Lyon, France
Title: Cooperation between syndecan 1 and CD81 contributes to hepatitis C virus infection of hepatocytes
Biography:
Eve-Isabelle Pecheur has completed her PhD in 1997 from University Paris XI and Post-doctoral studies from Groningen University of Medical Sciences (Netherlands). She leads her research group at the Cancer Research Center of Lyon. She has published more than 50 papers in reputed journals. She is serving as an Editorial Board Member of Antiviral Research, and as an academic Editor of PLoS ONE.
Abstract:
Background & Aims: The hepatocyte microenvironment at the vicinity of cell surface (a.k.a. glycocalyx) is rich in membrane-anchored proteoglycans which are receptors for extracellular matrix proteins, cytokines, growth factors, lipoproteins and infectious agents. The hepatitis C virus (HCV) infects hepatocytes, after its initial attachment to the heparan sulfate proteoglycan syndecan-1. Here we investigated the link between the hepatocyte microenvironment, HCV entry and infection. Methods: Studies were carried out by RNA silencing, immunoprecipitation, proximity ligation assays, immunofluorescence and confocal imaging, coupled to cross-correlation and statistical analyses. Results: Hepatocyte infection by cell culture-grown HCV or clinical isolates was inhibited after knockdown of syndecan-1 or xylosyltransferase-2, a key enzyme of proteoglycan biosynthesis. Simultaneous knockdown of syndecan-1 and CD81, a receptor of HCV entry, strongly inhibited infection, suggesting their concerted action. At early infection stages, syndecan-1 and virions colocalized at the plasma membrane, and were internalized along with CD81 in endosomes. Direct interactions between syndecan-1 and CD81 were revealed in primary and transformed hepatocytes by immunoprecipitation and proximity ligation assays. This underpins the relevance of this interaction to HCV internalization and infection. Expression of syndecan-1 and xylosyltransferase-2 was altered within days post-infection, and the remaining syndecan-1 pool colocalized poorly with CD81. Conclusions: Syndecan-1 plays an important role in HCV entry and infection, and may act in concert with CD81, as syndecan-1 is detected in complex with CD81. Infection modulates syndecan-1 and xylosyltransferase-2 expression, underscoring a profound reshuffle of the hepatocyte glycocalyx early in infection, likely required for settling optimal conditions of viral propagation.
Raffaella Romeo
University of Milan, Italy
Title: Chronic Hepatitis Delta Virus (HDV) infection: What do we need to know?
Biography:
Raffaella Romeo graduated from Medical School University of Milan in 1989. She is a specialist in Liver Disease since 1992, and completed her PhD in 1998. She did her Postdoctoral studies at Pasteur Institute Paris (France). She is a Visiting Scientist at NIH, Bethesda (MD). Since 2005, she is a elected member of the expert committee for virology and vaccines of the United States Pharmacopeia, Rockville, MD. She has a National Academic Qualification as Associate Professor of Gastroenterology since 2013. She has extensively worked in the area of molecular biology of hepatitis B, C and delta viruses as well as hepatocellular carcinoma. She is the author of several publications on international journals. She is also a invited speaker at several International meetings.
Abstract:
Chronic HDV infection has lately regained clinical importance because of the evidence of increasing prevalence in Western countries. Even though a systematic population’s screening is still not performed, main areas of prevalence are the Mediterranean basin, the Middle-East, Central and Northern-Asia, West and Central-Africa, the Amazonian basin, Northern South-America and the Asia-Pacific region. It is estimated a global burden of about 20 million cases worldwide. Epidemiological studies on genotypes distribution have demonstrated that different clinical courses may rely upon the presence of more virulent genotypes. Progressive forms of infection are reported from Far-East and South-America, where genotypes 2 and 3, respectively, are endemic. Genotype 1 is present worldwide associated to disease with variable course. Genotype 4, typical in the Far East, is characterised by a mild hepatitis. Genotypes 5-8, described in West and Central Africa, are still poorly studied, in terms of clinical course. The different clinical course determined by genotypes may depend upon different virion assembly efficiency as well as RNA replication fitness. Cirrhosis occurs within few years from HDV infection in about two thirds of cases, and there is a three-fold higher risk of progression to cirrhosis as compared to patients with chronic HBV mono infection only. Treatment of chronic HDV infection is difficult. The ideal drug would be able of inducing HDV clearance but also HBV clearance. Several attempts have been made with various drugs (IFN, PegIFN, Ribavirin, Lamivudine, Adefovir, Tenofovir) alone or in combination, with disappointing results. Attempts on looking for new antiviral compounds are currently ongoing.
André-Jean Remy
Perpignan Hospital, France
Title: Incidence of the hepatitis C in prison in France: Results of a study by POCT
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 C (HCV) rate is higher in the prisoners’ population than in the general’s one in France between 5 and 7% (INVS on 2004, PREVACAR). Prisoners accumulate risk factors before their confinement but the prison in itself represents a risk factor: Syringes or straw share, homemade tattoos, etc. Global incidence of HCV in France was 2700 and 4400 new cases per year. On the other hand HCV incidence in jailhouses was not known. Screening of HCV is systematically proposed in the entrance to detention in France but its renewal, recommended by the Methodological Guide of sanitary care is not still applied correctly. In this context, point of care testing (POCT) use could constitute an interesting alternative in classic serology and was recommended in French HCV experts report in 2014 and in national guidelines in 2015. Objective: Use HCV POCT in prison as a supplement to the classic serology to study the incidence of new HCV infections. Methods: HCV prevalence in our establishment is situated in national average around 7%. HCV serology realized by venous way was proposed to all incomers in Perpignan detention center. POCT was proposed to 3 types of prisoners: 1/refusal or impossibility of venous way 2/transfer of another penitentiary and previous negative serology 3/presence in detention 12 months old superior and previous negative serology. In case of positivity a FIBROSCAN and a complementary biological balance sheet are realized. Results: 333 HCV POCT was realized in 24 months: Group-1; 15 %, group-2; 27%, group-3; 58%. Two serologies were positive. The 2 inmates were imprisoned for more than 6 months and the viral load was positive. A patient had gone out in permission one week and a patient had never gone out of detention. The use of drugs was route of contamination in 2 cases. The calculated incidence was 3/1000 per year or potentially 470 new cases of HCV infection in France per year among the prison population (78246 prisoners on June 1st, 2015). Discussion/Conclusions: HCV POCT is useful in jailhouses because there are HCV high risk places. These routed of contamination could be more than 10% of HCV new cases. So it was also necessary to give harm reduction tools for all prisoners.
Vince Fragomeli
Nepean Hospital, Australia
Title: Hepatitis B and C care in the opiate substitution setting—An integrated nursing model of care
Biography:
Vince Fragomeli is a Clinical Nurse Consultant at Department of Gastroenterology and Hepatology in Nepean Hospital, Australia.
Abstract:
Hepatitis B and C are major global public health concerns with some 500 and 200 million worldwide cases respectively. Despite the availability of effective curative therapies for hepatitis C virus (HCV) and viral suppressive therapies for hepatitis B virus (HBV), to date only a minority of infected patients receive treatment throughout the world. In the general population, morbidity and mortality associated with chronic HCV and HBV infection is on the rise. Increased notifications of advanced liver disease and hepatocellular carcinoma are also rising at an alarming rate. This situation is more pronounced in the Opioid Substitution Therapy (OST) setting where people living with hepatitis B or C historically have been reluctant to access liver services. In Australia, an estimated 41% to 68% of people who inject drugs (PWID) are HCV-positive and between 28% and 59% of users are estimated to have been exposed to HBV. Although current treatment guidelines suggest that active drug use should not preclude people from HCV treatment, uptake of therapy thus far has been low to say the least. Patient, physician, social, and logistical-related barriers contribute to the low uptake of HCV/HBV treatment among PWID. Traditional means of managing HCV/HBV infection, that is, referral to a secondary or tertiary health centre, to date has proven to be an ineffective model for providing assessment and treatment options for this patient population. Approximately 50,000 Australians receive OST through a range of services, including public and private clinics, thus this setting is an ideal target for identifying and treating people at risk for and already infected with HBV and HCV. This is of particular relevance with the emergence of all-oral direct antiviral agents (DAA) that are more tolerable and efficacious than conventional interferon subcutaneous injection based treatment. This paper will describe the creation and functioning of a multidisciplinary, nurse-led model of care initiated by a teaching hospital in Sydney, Australia, that integrates viral hepatitis screening, assessment and treatment into the OST setting. In the world of escalating burden of liver disease and healthcare costs, this nursing model of care has been effective in enhancing access to HBV/HCV services among the marginalized injecting drug use population.
Xueshan Xia
Kunming University of Science and Technology, China
Title: High HCV infection in a village at Luxi county in southwest China and its phylogenetic analysis
Biography:
Xueshan Xia has completed his PhD from Chinese Academy of Science and then successively was taken as visting scholar in National Institute of Infectious Disease of Japan and Mecine School of University of Utah. He is the Dean of the FACULTY of LIFE SCIENCE and Technology, Kunming University of Science and Technology, and the Director of Yunnan Provincial Center for Molecular Medicine. He has published more than 25 papers in reputed journals and has been serving as a reviewer of several journals.
Abstract:
Occasionally, a sharp increasing of HCV infection was found in People’s Hospital of Luxi county, Yunnan province of China. The most of these outpatinets are resided in Baima-Zhehei, a common village in Luxi. A total of 900 plasma samples were collected including 746 from adult and 154 from children less than 12 years old. ELISA for HCV antibody and RT-PCR were conducted to detect HCV infection. Of 746 adult participants, the HCV sero-positive rate is 41.95% (313/746) and HCV RNA positive rate is 32.04% (239/746). Comparatively, the sero-positive (0.65%, 1/154) and RNA positive (0.65%, 1/154) rates of children are significant lower than that of adults. According their informed risk behaviors, using of inadequately sterilized syringe is deduced as major risk factor for their HCV infection occurred at least 15 years ago. The fragment of NS5b gene were amplified and subsequently sequenced. Of randomly selected and successfully genotyped 71 samples, 3b was determined as the predominant HCV subtype (73.23%, 52/71), followed by 1b (15.49%, 11/71) and 2a (8.45%, 6/71). As the common HCV genotypes in China, 1b and 2a haven’t been detected as the predominant HCV genotype. Alternately, 3b, being identified frequently in neighbored Southeast Asian countries, was found as the most prevalent HCV genotype. Moreover, 2 cases of 6n, the common HCV genotype in SE Asia, were simultaneously revealed in this population. In MACC analysis using Beast software. these 3b strains were shown to have high relationship with 3b strains in SE Asian countries. Surprisingly, their original time was estimated as 1940s, it is far different with our suspected 1980s, the start time of opening and reforming policy in China. These findings enriched our understanding on HCV epidemic in Yunnan and is helpful for HCV prevention and controlling.
Yuming Wang
Third Military Medical University, China
Title: Using NUCs in prevention of mother-to-child transmission of HBV: To treat or not to treat?
Biography:
Yuming Wang is currently the Academic Leader in Department of Infectious Diseases, Southwest Hospital, Third Military Medical University in Chongqing. He graduated from Guiyang Medical College and then received his Post-graduate training at Third Military Medical University. He studied in Gifu University in Japan and then in UCSD and Johns Hopkins University. He is mainly devoted to the research on hepatitis B and C. He has been chief editor of 16 monographs, associated editor for 31 monographs and published more than 400 papers, including Gastroenterology, Hepatology and CGH. He received the 2nd Class Award of National Scientific and Technology in 2004.
Abstract:
Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains a world concerned question. Despite the administration of HBIG and hepatitis B vaccines after birth, the immunoprophylaxis failure leading to significant MTCT rates ranging from 8% to 32% has been reported among HBeAg positive mothers with high HBV DNA levels. Recently, antiviral drugs, especially nucleoside analogues (NUCs), have been used in clinical studies to prevent perinatal infection. All current oral anti-HBV drugs are FDA pregnancy category C, except telbivudine (LdT) and tenofovir disoproxil (TDF) and emtricitabine (FTC), which are pregnancy category B drugs. Drugs in category B are confirmed safe to fetus in animal reproduction studies, while those in category C are not well defined. LAM was firstly used in HBV-infected mothers, and showed a satisfactory safety profile in late pregnancy. LdT and TDF has potent, specific, and selective anti-HBV activity when administered by an oral route, and no mutagenic, carcinogenic effects, appreciable embryonic or fetal toxic effects were found, especially in women during their reproductive period. In our studies, LdT and TDF have demonstrated a wonderful long-term safety profile in both mothers and their infants. They have also demonstrated an excellent efficacy—as high as 100%—in the protection rate of mother-to-infant transmission. Therefore, administration of NUCs therapy to HBV carrier mothers during pregnancy is effective in reducing MTCT. Furthermore, it is known that pregnant women are in an immune allergic status and LdT was reported to have the beneficial functions of immunoregulation in HBV-infected pregnant women.
Wei-Ting Wang
National Chiao-Tung University, Taiwan
Title: The regulation and functional roles of the HCV NS5A-stabilizing factor, Y-Box binding protein 1, in HCV life cycle
Time : TBD
Biography:
Wei-Ting Wang has completed her PhD from National Yang-Ming University and is now a Post-doctoral fellow in National Chiao-Tung University.
Abstract:
Chronic hepatitis C virus (HCV) infection is one of the leading causes of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). More than 130 million people are now infected with HCV worldwide. Since there is no available vaccine, HCV infection remains a serious global health problem. Recently, the HCV nonstructural protein 5A (NS5A) has emerged as a novel anti-HCV drug target and the roles of this enigmatic viral protein in HCV propagation have been largely uncovered. Although without enzymatic activity, HCV NS5A plays multiple roles in HCV propagation and participates in almost every stage of HCV life cycle, including HCV RNA replication and infectious virus production. Our recent studies have shown that the cellular protein Y-box binding protein 1 (YB-1), a known HCV cellular cofactor, interacts with and protects NS5A from rapid degradation by which YB-1 regulates the early stage of HCV RNA replication and infectious HCV virion production. Our studies then revealed that the NS5A-stabilizing activity of YB-1 is tightly controlled by a single phosphorylation of YB-1 at serine 102 which is probably mediated by HCV-infection-induced PI3K/Akt signaling. Taken together, our results have not only disclosed a probable regulatory mechanism for HCV to control the level of its own viral protein through cellular factor, but also revealed a potential strategy for developing novel anti-HCV drugs.
Alphonsine Kouassi-M Bengue
University Felix Houphouet Boigny, Cote d Ivoire
Title: Hepatitis B virus in Cote d Ivoire (West Africa)
Biography:
Kouassi-M'bengue A is a Microbiologist, Professor of Bacteriology and Virology at UFR of Medical Sciences in Abidjan since 2008 and Head of Department of Microbiology at UFR of Medical Sciences of Abidjan since 2015. Her research areas are virological study of viral hepatitis; quality management of microbiology laboratories; antibiotic resistance. She has more than 10 publications on viral hepatitis B and C and hepatocellular carcinoma.
Abstract:
Background: Viral Hepatitis B infection is a serious public health problem. Africa and Asia are endemic with more than 8% of seroprevalence. In Asian countries like Taiwan, remarkable success in reducing long term complication has been reported by vaccination. World Health Organization guidelines advocate that the first dose of infant HB vaccine be administered in the first few days of life. However in most of sub Saharan countries, especially in Côte d'Ivoire the first dose is administered at six weeks of age. Universal infant vaccination with the hepatitis B (HB) vaccine has been implemented within Expanded Programmed Immunization (EPI) in 2003. Collaborative agreement between National hepatitis infection Control Programs and private partner had permitted to reduce cost of screening in laboratory. Objectives: This study sought to determine prevalence and factors associated with HBV in children and adults populations in Abidjan (Cote d’Ivoire). Methods: A cross-sectional study was conducted at Pasteur Institute of Cote d’Ivoire from July 2015 to February 2016. Ethical clearance for this study was obtained from National Ethical and Research Committee. We obtained informed written consent from participants of the study and administered a questionnaire related to socio demographical information and risk factors of possible route transmission HBV and HCV. Blood sample were collected for the detection of HBS Ag, Ab –HBc IgG and Ab –HCV. Serological analyses were performed by Cobas e 601 (Roche R). Data was entered into EPI INFO 3.5 and analyzed by logical R. Qualitative variables were compared using the Fisher exact test and quantitative variables by analysis of variance (ANOVA). Results: A total of 1801 patients were recruited; among them 138 children (7.7 %) aged 0 to 15 years and 1663 adults (92. 3%). Sex ratio was 1.2 (964/837). The overall prevalence of HBsAg was 30. 9% (557/1801). Concerning children 12.3% (17/138) were HBs Ag-positive. About HCV, the overall prevalence rate was 5.3% (95/1687), no child was HCV positive. Co- infection HBV /HCV rate was 0, 95% (16/1687). Undertaking age, blood transfusion, sharing of needle were associated with HCV (P=0.01). HBV was associated with sex, youth, promiscuity, low socio economical level, tattooing ((P<0.001; p<0.001; p=0.007; p=0.01; p=0.002). Conclusion: Our finding shows a high prevalence of HBV and measures to reduce the disease and transmission burden must be introduced.
Deepak Bansal
Dayanand Medical College and Hospital, India
Title: Fibroscan, a non-invasive method, can effectively predict portal hypertension and high grade oesophageal varices in patients with liver cirrhosis
Time : TBD
Biography:
Deepak Bansal has completed his fellowship (DM) in Gastroenterology in 2015 from Dayanand medical college and hospital, Ludhiana, India and is presently serving as Assistant Professor in department of gastroenterology at government medical college and hospital, Chandigarh, India. He has participated and organized several gastroenterology conferences and has special interest in field of hepatology.
Abstract:
Liver fibrosis predicts presence of portal hypertension. Fibroscan which is based on transient elastography measures liver stiffness. Our study was conducted to evaluate whether fibroscan can effectively predict the presence of portal hypertension and of esophageal and gastric varices in patients with cirrhosis. We prospectively enrolled 201 patients with established case of cirrhosis between January 2013 and June 2014. Fibroscan was measured for each patient and additionally upper GI endoscopy was done. Results showed that 182 (91.9%) patients had evidence of portal hypertension with mean fibroscan value of 30.01± 22.15 kpa and 16 patients had no evidence of portal hypertension on upper GI endoscopy with mean fibroscan value of 18.93+/-18.26kpa ( p value=0.050). The mean fibroscan value of patients (53/102) with high grade oesophageal varices was 40.81±22.88kpa. Subgroup analysis shows that fibroscan can predict high grade oesophageal varices (grade II + III vs. grade I) (p value=0.008). The cut off value of fibroscan for detection of portal hypertension was 29.37kpa, with 94.59% sensitivity. This indicates that fibroscan is a very useful test for detection of portal hypertension. Cut off value of fibroscan, for presence of high grade varices was 38.54kpa with negative predicted value of 81.46% which indicates fibroscan can effectively predict presence or absence of high grade oesophageal varices and thus upper GI endoscopy applied selectively to the patients. Thus, our study shows that fibroscan is very useful non-invasive test for detection of portal hypertension and predicting high grade oesophageal varices.
Parul Verma
Purdue University, USA
Title: A lipidomic analysis for Non-Alcoholic Steatohepatitis (NASH)
Time : TBD
Biography:
Kouassi-M'bengue A is a Microbiologist, Professor of Bacteriology and Virology at UFR of Medical Sciences in Abidjan since 2008 and Head of Department of Microbiology at UFR of Medical Sciences of Abidjan since 2015. Her research areas are virological study of viral hepatitis; quality management of microbiology laboratories; antibiotic resistance. She has more than 10 publications on viral hepatitis B and C and hepatocellular carcinoma.
Abstract:
Background: The mechanism underlying the transition from simple steatosis to the more severe form NASH remains unclear thus far. Aim: To investigate the lipidomic profile alteration during the transition of non-NASH to NASH in human livers, and to identify hepatic lipid biomarkers which can discriminate between NASH and non-NASH liver samples. Materials & Methods: Two independent sets (n=119 and n=106) of liver tissue samples collected from transplantation donors without heavy alcohol intake and viral hepatitis were characterized for histology. Lipidomic profiling was conducted for both sample sets. Liver tissues were classified as non-NASH or NASH. For lipidomic analyses, we use the first set as a discovery set (n=119) and the other as a validation set (n=106). A multivariate analysis was performed to identify lipids that discriminate NASH and non-NASH samples accurately. Elastic net logistic regression along with 10-fold cross validation was used. Validation was conducted using lipidomics data of 106 liver tissue samples obtained independently from another data set. Results: We found that 75 phospholipids are significantly different between NASH and non-NASH samples in the discovery set (p<0.01), among which 52 (69%) remained significant in the validation set (p<0.05). The majority of these lipids are phosphatidylcholines (PCs) and ester phosphatidylcholines (ePCs). 10 lipids (p<0.01) were found to discriminate NASH versus non-NASH accurately, with an AUROC (Area Under the Receiver Operating Characteristic) curve = 0.89. The same 10-lipid signature produced an AUROC of 0.92 in the validation set, with 3 lipids remained significant (p<0.05). By focusing on these 3 lipids that are significantly associated with NASH in both sets, we observed an AUROC of 0.83 and 0.82 in the discovery and validation data set, respectively. Conclusion: Our study highlighted the important role of phosphatidylcholines in the development of NASH. Further investigation of these lipids among larger biopsy-proven NASH samples as well as in serum samples are warranted.
M Abdel Samie
Menoufiya University, Egypt
Title: Increased liver stiffness measurement values using transient elastography in Egyptian patients with acute viral hepatitis
Biography:
Mohamed Abdel Samiee is a hepatologist at National Liver Institute in Menoufiya University, Egypt.
Abstract:
Background: Transient Elastography (TE) is a non-invasive and reproducible tool to assess liver fibrosis/cirrhosis. However, it remains to be determined if ALT flare interferes with fibrosis assessment. Aim: To determine the effect of increased serum ALT on liver stiffness measurement in patients with acute viral hepatitis. Methods: Thirty consecutive patients with acute hepatitis of virus etiology with elevation of liver enzymes (>10 folds of ULN) were prospectively included. Blood samples were collected and TE was done initially and after resolution of hepatitis and after normalization of liver enzymes. Patients with high BMI which could affect fibroscan and patients with cirrhosis were excluded. For determination of the etiology of hepatitis, a detailed physical examination, history taking and laboratory tests were performed in all patients. Results: Patients were 32.87±10.2 years old and males were 14 (46.7%). In all patients, the degree of liver stiffness at the time of the peak increase in aminotransferases exceeded the cutoff values proposed for the prediction of significant fibrosis or cirrhosis. The mean value of LSM at the time of inclusion in the study was 13.91±6.7 kPa and the mean value of LSM after resolution of hepatitis was 7.7±3.08 kPa. A progressive significant reduction in liver stiffness values was observed (P<0.01) in the follow-up period in parallel with the reduction of ALT levels (P<0.01). Moreover, a statistically significant, positive correlation between ALT and LSM at the onset of acute viral hepatitis was found (r=0.38, P<0.05). No significant correlation was found between increased total bilirubin level and LSM (r=0.3 and P>0.05). Reduction of mean value to 6.21±1.14 kPa was observed in 10 patients after 1 year of ALT normalization. Conclusion: TE has not demonstrated reliable diagnostic accuracy in patients with acute viral hepatitis.
Md Kamrul Hasan Chowdhury
University of New South Wales Australia, Australia
Title: Niclosamide blocks glucagon phosphorylation of serine 552 on β-catenin leading to a reduction in cyclin D1 and c-Myc expression in primary rat hepatocytes via PKA signaling
Biography:
Md Kamrul Hasan Chowdhury has completed his Bachelor of Pharmacy from the University of Development Alternative (UODA), Bangladesh. Following his Bachelor’s degree, he has received a scholarship for studying Master of Science (MSc) in Pharmacogenomics at Inje University, College of Medicine, South Korea. After graduating from Inje University, he successfully obtained a competitive PhD Scholarship UIPA (University International Postgraduate Award) from the University of New South Wales Australia, Australia.
Abstract:
Recently it has been found that glucagon is able to activate the β-catenin signaling pathway leading to increased cyclin D1 and c-Myc expression in liver. Therefore, the main aim of this study is to determine if the effect of glucagon activating β-catenin signaling leading to increased target gene expression is mediated through cAMP activation of protein kinase A. Primary rat hepatocytes were incubated with insulin, glucagon or epinephrine and a range of inhibitors of PI 3-kinase, Wnt, mitochondrial uncoupler (niclosamide) or PKA inhibitors to dissection out the pathway leading to increased serine 552 phosphorylation of β-catenin following glucagon exposure. Western blot and real-time PCR were used. In primary rat liver cells, we found that short exposure of glucagon or epinephrine caused a rapid increase in serine-552 phosphorylation on β-catenin that leads to increased cyclin D1 and c-Myc expression. Both glucose and insulin had no effect on this pathway. A range of PI 3-kinase and Wnt inhibitors were unable to block the effect of glucagon phosphorylating β-catenin. Interestingly, both niclosamide and the PKA inhibitor H89 blocked the glucagon effect on β-catenin signaling leading to a reduction in the target genes expression. We have identified a new pathway via glucagon signaling that leads to increased β-catenin activity that can be reversed with the antihelminthic drug niclosamide which has recently shown promise as a potential treatment of type-2 diabetes (T2D). This novel finding could be useful in liver cancer treatment particularly in the context of T2D with increased β-catenin activity.
Biography:
NA
Abstract:
Libya is one of the countries where hydatid disease is endemic. A team of doctors reviewed retrospectively a total of 400 patients with hepatic hydatid cysts and were operated at Zliten University Hospital over the period of 24 years. The team of doctors looked for the clinical presentations of hepatic hydatid cysts. Most patients experienced abdominal pain or abdominal mass and few patients came to surgery department with rare presentation like obstructive jaundice. The obstruction of common bile duct was caused by the big cyst compressing on the bile duct or by the daughter cysts or hydatid membrane went into the bile duct. 49 patients whose main presentation involved abdominal pain and jaundice had been subjected for ultrasound scan and CT scan. All had open surgery, with two patients dying due to multiorgan failure, four patients developed recurrence of the hydatid, seven patients had bile leak which stopped spontaneously and three patients developed wound infection. All patients were cured from jaundice by surgery. In this presentation, the author would like to present new technique for common bile exploration in case of hydatid induced obstructive jaundice.
Ansoumane Kourouma
Huazhong University of Science and Technology, China
Title: The effects of 4-nonylphenol administration induced oxidative damages in liver and contributes to hepatic steatosis in male rats
Biography:
Ansoumane Kourouma has completed his PhD from Huazhong University of Sciences and Technology and Master’s degree in Biotechnology from University of Oriente, Santiago de Cuba, Cuba. He is a Lecturer in Toxicology at University of Gamal Abdel Nasser of Conakry, Guinea. He has published more than 10 papers in reputed journals and has participated in several conferences and workshop.
Abstract:
An emerging literature suggests that early life exposure to 4-nonylphenol (4-NP), a widespread endocrine disrupting chemical, may increase the risk of metabolic syndrome. In this study, we investigated the hypothesis that intraperitoneal administration of 4-NP induce hepatic steatosis in rat. 24 males Sprague-Dawley rats were administered with 4-NP (0, 2, 10 and 50 mg/kg b.wt) in corn oil during 30 days. Liver histology, biochemical analysis and gene expression profiling were examined. After treatment, abnormal liver morphology and function were observed in the 4-NP-treated rat, and significant changes in gene expression as indicator of hepatic steatosis and apoptosis were observed compared with controls. Up-regulated genes involved in apoptosis, Hepatotoxity and OS, increased ROS and decrease of antioxidant enzyme were observed in the 4-NP exposed rat. Extensive fatty accumulation in liver section and elevated serum SGOT, SGPT, LDH and γ-GT were also observed. Incidence and severity of liver steatosis was scored and taken in to consideration (steatosis, ballooning and lobular inflammation). Hepatocyte apoptosis could promote NAFLD progression; Fas/FasL, TNF-α and Caspase-9 mRNA activation were important contributing factors to hepatic steatosis. These findings provide the first evidence that 4-NP affects the gene expression related to liver hepatotoxicity, which is correlated with hepatic steatosis.