Scientific Program

Day 1 :

Keynote Forum

Maxwell Chait

Columbia University, USA

Keynote: Lower GI bleeding in patients with cirrhosis

Time :

Biography:

Maxwell Chait is a Fellow of the American College of Physicians, American College of Gastroenterology, American Gastroenterological Association and the American Society for Gastrointestinal Endoscopy. He is a Practicing Gastroenterologist and is an Assistant Professor of Medicine at the Columbia University, College of Physicians and Surgeons in New York City. He has authored numerous publications in reputed journals. He is the Editor-in-Chief of the Journal of Liver Disease and Transplantation and serves on the Editorial Board of the World Journal of Gastrointestinal Endoscopy.

Abstract:

Lower gastrointestinal bleeding (LGIB) is an important cause of morbidity and mortality in patients with cirrhosis. It occurs in approximately 20% of all patients who present with gastrointestinal bleeding (GIB) with cirrhosis. Gastrointestinal diseases that cause LGIB in patients with cirrhosis include specific vascular diseases, inflammatory diseases and bowel ischemia. However, in patients with less severe cirrhosis and advancing age, the causes are much like the general population and must also be considered. The incidence and severity of LGIB in patients with cirrhosis depends upon the incidence of specific gastrointestinal diseases, coagulopathy, co-morbid diseases and polypharmacy. The evaluation and treatment of patients is adjusted to the rate and severity of hemorrhage and the clinical status of the patient and may be complicated by the presence of visual, auditory and cognitive impairment due to hepatic encephalopathy. Bleeding may be chronic and mild or severe and life threatening, requiring endoscopic, radiologic or surgical intervention and methods to reduce portal hypertension.

Keynote Forum

Vincenzo Neri

University of Foggia, Italy

Keynote: Acute Pancreatitis Treatment

Time :

Biography:

Vincenzo Neri is a Full Professor of General Surgery, University of Foggia (2002-today), Department of Medical and Surgical Sciences. He is the Director of the Division of General Surgery (1997-today) and Director of Residency School of General Surgery, Policlinic University of Foggia (2008-today). He has done his graduation in Medicine and Surgery from the University of Bari in the year 1970. He was an Assistant Professor since 1974 to 1982 (University of Bari, Italy). He was an Associate Professor from 1982-2001 (University of Bari, Italy).  During ERASMUS-Program 2010-2011, he has presented his work in a seminar on Cystic tumors of the pancreas at the in the University of Gent (BE). He was the President of the Course of Degree of Medicine and Surgery, University of Foggia from 1996 to 2002. He was the Director of Department of Surgical Sciences, University of Foggia, from 2002 to 2008.

Abstract:

Acute pancreatitis (AP) is a complex disease with various etiology, most frequent biliary and alcoholic. Clinical presentation shows different degree of severity with biphasic evolution. The aim of this presentation is to evaluate the surgical procedures with mini-invasive approach as preferred choice in patients with pancreatitis. Biliary lithiasis and excessive alcohol consumption are the most frequent causes, reaching as a whole the total incidence of 80%. Moreover, numerous other causes of pancreatitis are recognized, which on the whole represent 20% of the total. In our Institution from 1998 to 2016, we have observed and treated 342 pancreatitis, 328 acute biliary pancreatitis and 14 chronic alcoholic pancreatitis. Mean age was 49 years (Range: 30-86 y). Male female ratio was 1:1,33. Biliary etiology was confirmed in 328 patients including 22 patients with recurrent unexplained pancreatitis at initial etiological assessment. The clinical morphological assessment of 328 acute biliary pancreatitis was the following: mild 185, moderate-severe 71, severe 55 and early severe 17. We employed a biphasic therapeutic program to control and treat general complications (SIRS, MODS) in the first phase. In biliary pathogenesis endoscopic retrograde cholangiopancreatography/endoscopic sphinterotomy ERCP-ES to assure papillary patency after cholestasis verification. In the second phase control and treatment of pancreatic gatherings and belated acute postnecrotic pseudocysts was done. In biliary pancreatitis, the therapeutic program includes assuring papillary patency and CBD cleaning with ERCP/ES. After ERCP, it is necessary to perform laparoscopic cholecystectomy (LC) to complete gallstones treatment. The timing of LC is connected with AP evolution because it is preferable to wait for the stabilization of the general conditions. Treatment of the later phase of AP consists in control and treatment of local complications: infections, hemorrhage, pancreatic and peripancreatic fluid necrotic collections. In summary, in APs it should be preferred the mini-invasive approach for various clinical manifestations.

  • Hepatitis B Hepatitis C Hepatitis Vaccination
Location: Endeavour
Speaker

Chair

Maxwell M. Chait

Columbia University, USA

Session Introduction

Paul Desmond

Hepatitis B Positive Trust, UK

Title: Hepatitis B Infection is now 30 times more common in UK than US children!
Speaker
Biography:

Paul has run the Hepatitis B Trust National Charity and helpline since 2010, some 10,000 HBV and HCV patients have been advised.  The Hepatitis B Trust produces guidance for 14 Industries, the Medical Profession and patients.  Paul has talked to hundreds of organisations about hepatitis B and C and advised on 500,000 hbv vaccinations, his online forum has reached 500,000 users.  Policy packs for Unions, Schools and Politicians are also produced.  Some 40 posters and videos have also been used tailored to different venues.

Abstract:

Campaigners for the Hepatitis B Trust today condemned 20 years of government failure to address our tripling Hepatitis B infections and accused the Department of Health of hiding them, especially among UK children, migrants and valuable key workers.

Trust Director of Communications, Paul Desmond said, “The UK is still continuing to under publicise the prevalence of this booming epidemic even in 2017, forty years after the test became available. We have received the last audit of 100,000 HPA hospital tests done to keep an eye on HBV from 2008 to 2015, and now it is published, the results are far worse than anyone dreamt possible.”

“The fact is our hospitals are reporting 1 in 64 adults and even more concerning 1 in 140 children in the UK are already incurably infected with HBV when tested.  This means our children are now testing 30 times more infected than their US counterparts, who are testing 1 in 5000 positive in their surveillance programs.  Our inner cities and their schools have suffered a massive boom in infections and we are still not being warned or using the vaccine effectively.  We are not being allowed to test enough to find out what help is needed among children, professions and migrants when there are onward infections and school and healthcare/high street outbreaks.”

Paul explains, “The reason why people need to know about HBV is we have 12 million adults and children at risk of infection and we estimate a fast growing 440,000 HBV positive people out there, mainly undiagnosed at risk of cancer.  People especially need to learn HBV is not rare like HIV with 90,000 UK infections; HBV is common with 2,000,000 UK infections and 500,000 unable to clear the virus.  Further HBV is not mild like Swine Flu, killing in the hundreds; it kills up to a third of the long term infected, potentially 166,000 lives in the UK.  And our non alcoholic liver deaths are booming fastest in the EU. 

People need to ask themselves why on earth they know about rare bugs and mild bugs and yet with a vast deadly threat like HBV we have 12 million citizens who have not been told they are at risk of infection and indicated for testing on the WHO Atlas for 20 years. Over the years the National HBV Helpline has received calls from thousands of patients, public and even health secretaries and doctors, all needing basic facts about HBV, all struggling to understand HBV and its risk.“

Paul continued “Citizens have a right to know how you catch HBV, how hundreds of millions of children catch it, how their schools are infectious, how their occupations may often be infectious or if the World Health Organisation has audited their nationality as being a more than 1 in 50 risk like Spain and the 100 other nationals we recommend for prompt safety testing and vaccination.“

 “Mothers have a right to know children cannot enter schools without HBV vaccination certificates in the rest of the world, that only zero migration Scandinavia and ourselves do not protect children from HBV. How anybody, never mind the Minister for Public Health can imagine we have the HBV  prevalence of Finland while gazing from the Commons at 3.8 million migrants from endemic areas in London alone is simply beyond any logic. Especially with the Department of Health refusing to test and guessing there are only 180,000 cases in the UK since 1993, while so many independent experts both here and overseas are seeing 500,000 or much nearer the EU average due to migration.”

In 2017 can our new UK Government finally enact the 1999 WHO Hepatitis Guidelines for testing?

Seth Kuranz

Decision Resources Group, USA

Title: The Global Burden of Hepatitis C: A 10-year Forecast
Speaker
Biography:

Mr. Kuranz is an epidemiologist at DRG specializing in the epidemiology of metabolic, renal and psychiatric disorders. He holds an MPH from Boston University.  Prior to joining DRG, he served as the coordinator of an international research project focusing on early adult development and substance abuse dependence.

Abstract:

Introduction: Hepatitis C virus (HCV) contributes substantially to the burden of disease worldwide. Modes of transmission and risk of HCV differ by geographic regions (WHO, 2016). The impact of HCV treatment on the future prevalence and incidence of HCV will vary based on rates of diagnosis and compliance.

Methods: To estimate the incidence and prevalence of HCV, we systematically reviewed the literature (DRG, 2017) and analyzed NHANES cycles 2007-2014 (CDC, 2016). We defined prevalent anti-body positive cases of HCV as individuals who received a positive result on an ELISA or equivalent test and, where possible, in combination with a RIBA. We defined HCV viremia as the presence of HCV RNA in the serum. We incorporated diagnosis and drug-treatment assumptions into out trend and these were applied to region-specific HCV genotype (Gower E, 2014) and cirrhotic distributions. The 10-year forecast incorporated demographic changes related to aging and population growth. When country-specific data were unavailable we extrapolated based on data from comparable countries. To estimate the number cases in each country, we multiplied the age- and gender-specific estimates presented in these studies by the UN population estimates for each forecast year (United Nations, 2016).

Results: Over the 10-year forecast, incident cases, prevalent anti-body positive cases, and viremic prevalent cases decreased substantially due to reduced risk in the population and improved treatment.  If rates of treatment and treatment efficacy were to remain constant over the forecast period, viremic HCV decreases by over 20% between 2017 and 2027. Assuming treatment becomes more readily available during the forecast period across all regions and that compliance remains relatively high, HCV will decrease to an even greater magnitude by 2027.

Conclusion: Viremic prevalence will decrease substantially in both higher-income and lower-income countries with the later experiencing the largest decrease in prevalence over the forecast period.

Speaker
Biography:

Dr André-Jean REMY, is Head of Hepatology and Gastroenterology Unit & Social Medicine Unit of Perpignan Hospital, and he is one of 41 viral hepatitis experts unit in France. Social medicine include jailhouse medical unit, retention center medical and primary care access unit. He is also Medical coordinator of Mobile Hepatitis Team, a new concept of HCV/HBV patients care from diagnosis to treatment. He is a Member of French hepatitis B and C guidelines follow-up national staff,  General Secretary of ANGH, 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; 50 articles in 2012 to 2016.

Abstract:

In hepatitis C, Drug users and inmates are a hard to screen population as well as to take over and treat. There is a common understanding that these patients have a delayed access to antiviral C treatment. French rulings published on June 10, 2016 could provide treatment by direct acting antivirals (DAA) to all these patients regardless of fibrosis stage. Since it’s creation in July 2013, the hepatitis mobile teams offers to all partner entities all or part of the following 15 services: 1. Training of socio-medical institutions staff with trimestral  days of exchange or on-demand and on-premises. 2. Prevention information sessions toward drug users in day-care or housing structures. 3. On-site HVC HVB HIV POCT screening. 4. BOUSSOLE 5 days a week Reception Information & Accompaniment. 5. On-premises mobile Fibroscan®. 6. Social evaluation & diagnosis by EPICES score. 7. Free biological check-up at the PASS (in case of absence of health care rights). 8. On-site specialised consultations. 9. LE FIL VERT: POCT & Fibroscan® in outdoor sites. 10. Rapid access to a close expert service called “RCP” (multidisciplinary meeting), obligatory in France before treatment acesss. 11. Mobile phone lending for patients. 12. Individual sessions of therapeutic education inside an ARS (Regional Health Agency) authorized program. 13. Therapeutic support groups (nurse, psychologist, sophrologist, nutritionist). 14.  Dedicated day hospital. 15. Expert patient support.

 

Patients and methods: The aim is to compare the average delay of access to DAA treatment in 2016 of all the patients of our centre (group 1) to the drug user patients (group 2) followed by specialised medico-social institutions (CSAPA/CAARUD), to excluded patients newly outdoor screened (group 3) with an EPICES score over 45 and inmates (group 4). The date of first contact was when the patient met the hepatitis mobile team nurse in CSAPA/CAARUD, screening date for the outdoor patients and date of detention for inmates. Was also calculated the average delay of access to RCP and the one between RCP and treatment day 0. Groups 3 and 4 patients were totally taken over by the hepatitis mobile team.

 

Results: 113 patients were included in this study on September 15, 2016. Average delay between first contact and treatment day 0 was of 10 weeks with differences among groups detailed in Table 1. Average access delay to treatment was of 98 days for group 2, 70 for group 3 and 57 for group 4. Average delay between first contact and RCP was respectively of 56/77/55 and 49 for groups 1 to 4. The difference would be due to average delay between RCP and treatment day 0. The delay difference was significant (p<0,05) between group 2 and 1. No significant difference was stated in groups 3 and 4 against group 1.

Conclusion: Drug users who are followed in a medico-social institution have by our experience a longer access to antiviral C treatment than inmates or excluded patients. This is explained by a shorter care pathway (screening-blood test-RCP-treatment) and calls for an organisation of “all-in-one” centres, set-up around a multidisciplinary team to the benefits of patients with chronic hepatitis C viral infection.

Time (days)

Total of patients

PWID in drug centers

Precarious outdoor screening people

Inmates

First contact to treatment

70

98

70

58

First contact to RCP

56

77

55

49

RCP to treatment

14

19

15

9

 

Speaker
Biography:

Bevin Gangadharan is a Research Associate in the Oxford Antiviral Drug Discovery Unit, University of Oxford headed by Professor Nicole Zitzmann. The main focus of his current research is to use proteomics to identify and validate novel serum biomarker candidates for NAFLD. He carried out his DPhil with Professor Nicole Zitzmann where he identified serum biomarker candidates for liver fibrosis in hepatitis C patients.

Abstract:

Background
Liver biopsy is the reference standard for assessing liver fibrosis and no reliable serum biomarkers are available to discriminate between the intermediate stages of fibrosis. We used proteomics to identify novel fibrosis biomarkers in hepatitis C patients with different degrees of liver fibrosis.

Methods

Novel liver fibrosis biomarkers were identified by analysing proteins in plasma/serum samples from controls and hepatitis C patients with varying stages of liver fibrosis using a proteomics technique: two dimensional gel electrophoresis (2DE). Identified markers were validated across all Ishak fibrosis stages and compared to the markers used in FibroTest, Enhanced Liver Fibrosis (ELF) test, Hepascore and FIBROSpect by Western blotting. For the most promising biomarkers, an antibody-free assay (parallel reaction monitoring using mass spectrometry) was used which detects tryptic peptides of the biomarkers and their fragments.

Results
Forty four candidate biomarkers for hepatic fibrosis were identified of which 20 were novel biomarkers of liver fibrosis. Western blot validation of all candidate markers using plasma samples from  patients across all Ishak fibrosis scores showed that the markers which changed with increasing fibrosis most consistently included lipid transfer inhibitor protein, complement C3d, corticosteroid-binding globulin, apolipoprotein J and apolipoprotein L1. These five novel fibrosis markers which are secreted in blood showed a promising consistent change with increasing fibrosis stage when compared to the markers used for the FibroTest, ELF test, Hepascore and FIBROSpect.

Conclusion
This study identifies 20 novel fibrosis biomarker candidates. The proteins identified may help to assess hepatic fibrosis and eliminate the need for invasive liver biopsies.

Terence T Lao

Chinese University of Hong Kong, Hong Kong

Title: Immune persistence after hepatitis B vaccination in infancy: Fact or fancy?
Speaker
Biography:

Terence T Lao is a specialist in Obstetrics, Gynaecology and Maternal-Fetal Medicine. He has received training in Hong Kong; London, UK; and Canada.  He is currently a Professor in the Department of Obstetrics and Gynaecology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. His clinical and research interests are oriented around maternal medicine, especially endocrine and hepatic problems, hypertension, and hepatitis, as well as the management of high risk pregnancy. He is a reviewer of many international journals, and serves on the Editorial Board of three. He has 442 publications, including abstracts, listed under Google Scholar.

Abstract:

The hepatitis B vaccine has been in use for more than three decades and its efficacy has been widely reported. In Hong Kong, excellent vaccine coverage through an efficient public health care system, together with supplemental programs and easy availability of the vaccine, meant that most young pregnant women, and university students at entrance, should have been protected. Yet data from Hong Kong has not indicated a progressive decline in maternal carriage of hepatitis B virus (HBV). On the other hand, significant increase in the prevalence of HBV infection and a positive correlation with age has been found in students at university entrance, and in young mothers aged 25 years or less. This paradoxical phenomenon is most likely related to clinical vaccine failure. A number of factors are involved, such as the failure to respond to a primary series of hepatitis B vaccination in infancy, the waning of antibody titres with age, and loss of anamnestic response in a significant portion of the vaccines. We have shown that up to one in five of children who had received a full course of hepatitis B vaccination in infancy failed to develop an immune response. Furthermore, among adolescents and young adults covered by the universal vaccination program in infancy, waning of antibody titres to non-protective levels and loss of anamnestic response are not uncommon by the time of university entrance, despite a low incidence of HBV infection. Taken together, there is concern for the purported life-long protection conferred by hepatitis B vaccination in infancy. The duration of protection should be re-examined in further studies and remedial measures considered if long term protection is found to be insufficient. Otherwise, the efforts to control HBV infection, especially in high endemicity regions, with universal vaccination in infancy would be rendered futile.

Ruchika Sharma

Decision Resources Group, India

Title: Hepatitis C and Sustainable Development Goals 2030
Speaker
Biography:

Dr. Sharma joined the DRG Epidemiology team in Bangalore in 2016. She specializes in developing epidemiological forecasts and has worked on indications related to the field of infectious disease and primary nervous system epidemiology. Her qualifications include an MPH with special focus on Epidemiology from the Post Graduate Institute of Medical Education and Research, India and a bachelor degree in dental surgery. Prior to joining DRG she was a fellow at the National Health Systems Resource Centre. She was also the resident dental surgeon at UCMS, New Delhi.

Abstract:

Introduction:. The WHO estimates 130-150 million people worldwide, living with chronic hepatitis C virus (HCV) infection and the number is increasing despite improved treatment1. In 2016, the WHO released a global health sector strategy on viral hepatitis based on the Sustainable Development Goals 2030 report1. It enlists targets to be achieved with regard to HCV incidence, diagnosis and treatment, taking 2015 as the base year. This analysis aims to understand the global impact of successful achievement of the WHO targets on viremic prevalent cases.

Methods: HCV viremia is defined as the presence of HCV RNA in the serum. A systematic review of published literature was carried out to extract prevalence, incidence, and genotype distribution data for 45 countries, in addition to an analysis of NHANES data2. Extracted estimates were trended to 2015 based on current diagnosis and drug treatment scenarios. Percentage changes according to the WHO targets were applied to 2015 to arrive at the number of cases in 2020 and 2030.

Results: Between 2015 and 2030, there is a considerable decrease in the number of prevalent viremic cases modeled according to the WHO targets. In 2020, the viremic prevalence is highest in Africa (1.54) and lowest in North America (0.76). In 2030, the viremic prevalence ranges from 0.15 in North America to 1.0 in Africa.

Conclusion: If the WHO targets are achieved, there would be a considerable decrease in the burden of viremic HCV. Results should be interpreted from a global perspective to better understand inequitable differences in the burden of HCV across geographic regions.

Speaker
Biography:

Julio Cesar Aguilar Rubido completed his PhD in Biological Sciences. Titular Investigator, Project leader Therapeutic Vaccine against Chronic Infectious Diseases. Main author of 12 patent applications, 2 book chapters, 3 Review articles, 55 original research articles, 11 clinical protocols (phase I to Phase IV), 60 scientific presentations (Oral + Posters) in international meetings. He is the Young member of the Cuban Academy of Sciences, Cuban Society of Immunology.

Abstract:

Chronic hepatitis B (CHB) infection constitutes a major cause of HCC, liver cirrhosis worldwide. HeberNasvac is a novel therapeutic vaccine based in the recombinant HBsAg and HBcAg. These proteins contain adjuvant and immunomodulatory properties that supported the clinical development of HeberNasvac. Materials & Methods: Four clinical trials evaluated the administration of HeberNasvac, three of them in CHB patients. Two studies were carried out in treatment-naïve patients and a third was conducted in non-responders to IFN- therapy. The viral load was monitored as main variable in all the studies involving CHB patients. Serological evaluations for HBe and HBsAg and their corresponding antibodies were also conducted. The transaminases, bilirubin and other liver and hematological markers were evaluated to assess product safety. Balb/c mice, rabbits and AAV HBV transfected/HLA double transgenic mice were used as models to evaluate the capacity of the nasal route of immunization to generate systemic and especially liver immune responses. Results: Clinical trials evidenced a significant reduction of the viral load to undetectable levels and under 104 copies/mL, both at end of treatment and after 24/48 weeks follow-up evaluations, evidencing the sustained control of the virus. Liver function tests and hematological variables evidenced the safety of this product. Serological responses were higher to PegIFN treatment. Action mechanism studies related to the route of immunization evidenced the role of the nasal route of immunization in the induction of T cells at the target organ, the liver. Conclusions: The vaccination with HeberNasvac is effective and safe, supporting its use as therapy against CHB infection. The studies of immunogenicity in novel model of CHB infection evidenced the effect of the nasal route of immunization in the liver homing of effector T cells. These results suggest that HeberNasvac may contribute as a novel treatment for CHB.

Abdulrahman A. Aljumah

King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia

Title: Epidemiology and Disease Burden of Chronic Hepatitis C in Selected Middle Eastern Countries
Speaker
Biography:

Dr. Aljumah is a consultant hepatologist and gastroenterologist at King Abdulaziz Medical City and Associate Professor, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia. He was graduated from Faculty of Medicine, Cairo University, Egypt. Then had obtained a diploma in internal medicine from the Royal Postgraduate Medical School, University of London, United Kingdom. This was followed by the Membership of The Royal College of Physicians of Ireland (MRCP), Dublin, Ireland and the Arab Board in Internal Medicine (ABIM), Arab Board Medical Specialization, Riyadh, Saudi Arabia. After that he completed 2 years Clinical Fellowship training program in (Gastroenterology, Hepatology & Liver Transplantation) from the Toronto Hospital, University of Toronto, Toronto, Canada. He was awarded the Fellowship of the Royal College of Physicians of Ireland (FRCP) Dublin, Ireland. Finally he was awarded a Master degree of Public Health in Epidemiology and Biostatistics (MPH), College of Public Health and Health Informatics, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia and Liverpool School of Tropical Medicine, UK.  Dr. Aljumah was the Associate Editor of the Saudi Journal of Gastroenterology and currently a member of the editorial board in; Journal of Gastroenterology and Hepatology Research, World Journal of Hepatology, SM Journal of Hepatitis Research and Treatment, and Journal of Archives of Clinical Gastroenterology. Additionally he is a reviewer for several international journals. He has published about 60 publications in different peer-reviewed journals and has been a speaker in multiple conferences.

Abstract:

The Middle East is a geographical region that includes areas in Southwest Asia and parts of North Africa. Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma and is the leading indication for liver transplantation. It was estimated that 170 million people are infected with HCV, with a worldwide prevalence of 3%. HCV is one of the main causes of mortality and morbidity globally. In the Middle East, HCV is a significant health concern, with some areas in the region categorized as having a high prevalence of HCV infection (1-3.5%). Egypt has the highest prevalence of HCV in the world (>15%).  It was estimated that currently there are at least 23 million people live with HCV infection in the countries of the Eastern Mediterranean Region. This is almost similar to the number of total HCV cases in the Americas and Europe together. The most prevalent HCV genotype in the Middle East region is genotype 4. However, genotype 1 is also common and the most prevalent among non-Arab countries in the region including Turkey, Iran and Cyprus. With the recent discovery of the new direct antiviral therapies, there have been significant developments in treatment strategies that have provided an opportunity to eliminate HCV infection in the near future. However, there are some major issues concerning HCV that still need to be tackled in the Middle East, particularly, the cost of new drugs and the difficulty of identifying patients with HCV infection. HCV remains however a substantial challenge in the Middle East. Important health and financial burden namely; the cost of new drugs and the difficulty of identifying patients with HCV infection are issues that need hard work. To establish public health strategies, more efforts are required for prevention and treatment programs.

Day 2 :

Biography:

Ann Kwong is an internationally recognized industry leader in antiviral drug discovery and development and a co-founder of HCV DRAG (HCV Drug Development Advisory Group), a consortium of industry, clinical trial, community, and regulatory leaders working to optimize HCV drug development.  Ann is the co-founder, President and CEO of Trek Therapeutics which is committed to developing affordable and accessible drugs to treat infectious diseases. Trek is conducting Ph2 clinical trials to develop a potentially best-in-class and affordable regimen to cure HCV.  Prior to Trek, Ann founded the infectious disease group at Vertex Pharmaceuticals and played a leading role in the discovery, development, and commercialization of VX-787, a PB2 flu inhibitor currently in Ph2, and telaprevir (INCIVEK), a HCV inhibitor with >$2B in sales (Kwong, et al. (2011). Discovery and development of telaprevir: an NS3-4A protease inhibitor for treating genotype 1 chronic hepatitis C virus. Nat Biotech 29:1-11.

Abstract:

Global eradication of HCV is possible because it is the only chronic virus infection that can be cured with a drug. The last decade has been a period of incredible advancements where the “Holy Grail” of an all-oral, highly tolerable therapy with a >95% SVR12 (sustained viral response or cure) rate for chronic HCV infections was achieved. However, high prices in many middle- and high-income countries have resulted in severely restricted access, straining private and public healthcare resources (even in high-income countries such as those in Western Europe, and the US). 

This situation has presented a significant impediment to the development of i) “test-and-treat” programs with inexpensive, decentralized, and rapid HCV RNA diagnostic assays; ii) affordable and accessible HCV drugs for all patients; and iii) a medical infrastructure that is able to treat all patients effectively and efficiently. Current HCV treatment is focused on treating a pool of rapidly diminishing, already-diagnosed patients. 3.4 million people in the EU have chronic HCV infections; this includes injection drug users, prisoners, and migrants. Depending on the country, ~50-90% of patients have not been diagnosed, and <10% of HCV patients are treated each year (Romania and Poland treat £ 2% of up to 1 million HCV patients).  Lack of timely diagnosis and cure increases the risk of liver cirrhosis, liver failure, liver cancer, and premature death. Within high-income countries, pockets of high unmet medical need also exist. Germany treated 20,100 patients in 2015 at a cost of €1.3 billion, yet they have 129,000 immigrants alone with HCV. In the United States, 1 in 3 HCV-infected people pass through the US Corrections Systems each year and the vast majority remains untreated.

Trek Therapeutics, PBC (Trek) is an infectious disease pharmaceutical public benefit corporation (PBC) based in Cambridge, MA, USA whose mission is to make affordable and accessible drugs to treat infectious diseases AND be profitable. Trek has an integrated management team with deep experience in discovery, clinical & CMC development, pricing and medical affairs, and has helped launch 8 antiviral drugs, including 5 HCV drugs. Trek is developing drugs to address the remaining barrier to hepatitis C virus (HCV) care by providing ACCESS to curative treatment.  The goal is to develop an HCV regimen at a $10,000 price point that is as good or better than the standard of care  (~$40,000 to $95,000/treatment). Trek will drive revenue with a volume-based, value-driven, “test-and-treat” strategy.

 Trek has in-licensed a pipeline of four HCV drugs, most of which are second- and third-generation drugs with Phase 2 and 3 clinical data. They include TD-6450 (third-generation NS5A inhibitor from Theravance), MIV-802 (second-generation nucleoside inhibitor from Medivir), faldaprevir (FDV, second-generation NS3 protease inhibitor from Boehringer Ingelheim), and VX-222 (first-generation non-nucleoside inhibitor from Vertex).

Trek’s clinical program is risk-reduced with favorable Ph2a clinical data: Patients receiving FDV + TD-6450 + ribavirin for 12 weeks had no SAEs or discontinuations, and achieved SVR12 (viral cure) in 16/16 patients with HCV genotype (GT) 4, and in 14/15 patients with HCV GT1b. Trek is developing 3 HCV regimens:  TRK-1 to treat HCV GT1&4 and launch in 2021 in the EU; TRK-1SD (short duration) will also target GT1&4 in the US, EU, and Mexico and launch in 2022; TRK-2/3 will target GT2&3 in high prevalence countries, and launch in 2023.

Conclusion
It is not enough to have highly effective and safe HCV treatment regimens.  Industry, academia, patients and their families, non-government organizations (NGOs), ministries of health, regulators, and the investment community need to collaborate to apply the same ingenuity, energy, and funding used to develop highly effective HCV drugs, to eradicate HCV. Trek will partner with providers, insurers, patients, and government health authorities to promote testing and other care necessary to identify and cure patients, and to help the World Health Organization (WHO) reach their goal of eliminating HCV by 2030.

Keynote Forum

Ming Luo

Georgia State University, USA

Keynote: A Virus-like Particle of HBV preS Elicits Robust Immune Responses

Time :

Biography:

Dr. Ming Luo works on structures of viruses by employing X-ray crystallography and cryo-EM image reconstruction. His primary studies focus on RNA viruses and HBV. He discovered that the nucleocapsid of negative strand RNA viruses sequestered the genomic RNA by polymerization of a capsid protein. During viral RNA synthesis, the nucleocapsid is used as the template in coordination with the viral polymerase. With his knowledge of virus structure, he has been involved in design of novel antiviral drugs and vaccines. His work resulted in a FDA-approve flu drug. For this study, he combines the proteins from influenza virus and HBV to generate a preS VLP that is highly immunogenic. Further development of preS VLP prophylactic and therapeutic vaccines is in progress.

Abstract:

The preS antigen of hepatitis B virus (HBV) corresponds to the N-terminal polypeptide in the large (L) antigen in addition to the small (S) antigen. The virus like particle of the S antigen is widely used as a vaccine to protect the population from HBV infection. The presence of the S antigen and its antibodies in patient blood has been used as markers to monitor hepatitis B. However, there is very limited knowledge about the preS antigen. Previous studies of preS employed recombinant preS proteins or polypeptides from preS. These molecules do not have the proper folded structure, nor proper post-translational modifications. We generated a virus-like particle (preS VLP) that is formed by a chimeric protein between preS and hemagglutinin (HA), and the matrix protein M1 of influenza virus. preS VLP was produced from 293T cells. The HBV preS antigen is displayed on the surface of preS VLP. Asn112 and Ser98 of preS in VLP were found to be glycosylated and O-glycosylation of Ser98 has not been reported previously. Biochemical characterization confirmed that preS in VLP was properly folded. The preS VLP shows a significantly higher immunogenicity than recombinant preS, eliciting robust anti-preS neutralizing antibodies. In addition, preS VLP is also capable of stimulating strong preS-specific T cell responses in Balb/c mice and HBV transgenic mice. Furthermore, preS VLP immunization provided protection against HBV challenge in mice. The data clearly suggest that this novel preS VLP could recapitulate the immunological properties of the L antigen in HBV particles, and can be potentially developed into prophylactic and therapeutic vaccines.

  • Liver Diseases Pancreatic Cancer Hepatocellular Carcinoma
Location: Endeavour
Speaker

Chair

Seth Kuranz

Decision Resources Group, USA

Session Introduction

Maxwell M Chait

Columbia University, USAAdvances in Hepatology

Title: Advances in Hepatology
Speaker
Biography:

Maxwell M Chait 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 boards of several journals including 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 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 these 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.

Speaker
Biography:

Animesh Dhar, PhD did his PhD from University of Calcutta in Physiology in 1982. Dr. Dhar did his post-doctoral training in University of Puerto Rico in Biochemistry and University of Missouri-Columbia in Pharmacology. Dr. Dhar is now an Associate Professor in the Department of Cancer Biology in the University of Kansas Medical Center (KUMC) .Dr. Dhar has published more than 50 publications in the high impact journals and about more than 10 reviews in the area of his research. Dr. Dhar is a member of several scientific society including American Association of Cancer Research, American Association of Advancement of Sciences, American Association of Biochemistry and Molecular Biology etc. He also served as ad-hoc grant reviewers in study sections including National Cancer Institutes, Department of Defense etc. Dr. Dhar’s research are focused on preventive and therapeutic approaches in pancreatic cancer. Dr Dhar’s research has been funded by NIH and Genzada Pharmaceuticals.

Abstract:

Background: Novel therapeutic targets are needed to treat pancreatic cancer because nothing is available for this devastating disease. GZ17-06.02, combination of novel natural compounds, contains anti-cancer properties in several cancers. Therefore, we hypothesize that GZ17-06.02 will inhibit tumor progression and metastasis in PDAC by suppressing cancer stem cells (CSC) and sonic hedgehog (SHH) pathway.

Methods: We have determined cell proliferation, pancosphere formation and apoptosis following treatment of different doses GZ17-6.02 in human pancreatic cancer cells. Orthotopic pancreatic cancer model in athymic nude mice was developed and GZ17-6.02 was given orally for 20 days. Proliferative markers, pEGFR/pAkt and apoptotic markers, Bax- Bcl-2- Caspase3 and also metastatic markers, MMP-2 and MMP-9 were measured in primary and metastatic tumor tissues. SHH pathway was determined using western blot, immunohistochemistry and cellular thermal shift assay (CETSA). Bioavailability through oral delivery of GZ17-6.02 in mice demonstrated rapid clearance from circulation and showed significant absorption and distributed quickly in different tissues. 

Results: GZ17-6.02 inhibits proliferation of pancreatic cancer cells in a dose and time-dependent manner. GZ17-6.02 induced apoptosis in both in vitro and in vivo pancreatic cancer. GZ17-6.02 significantly inhibited EGFR and Akt phosphorylation. Furthermore, GZ17-6.02 decreased the number and size of the pancospheres and inhibited CSCs markers such as DCLK1, Lgr5, EpCAM and Sox9. GZ17-6.02 inhibited SHH and the downstream signaling pathway including SUFU, Gli1 and Gli2. Significant interaction of GZ17-6.02 with SHH was found using CETSA assay. Metastatic markers, MMP-2 and MMP-9 activity increased in the tumors. GZ17-6.02 treatment down-regulation of proliferative and anti-apoptotic genes using RNAseq data. GZ17-6.02 has also been detected in different tissues particularly in liver when it is given orally.

Conclusion: GZ17-6.02 significantly reduces tumorigenesis and metastasis in both in vitro and in vivo pancreatic cancer models through impairment of CSCs and SHH pathway.

Martin Gasser and Ana Maria Waaga-Gasser

University of Wuerzburg, Germany

Title: Toll like receptors promote auto regulative tumor cell growth and growth factor expression in pancreatic cancer
Speaker
Biography:

Martin Gasser has his expertise in surgical oncology and clinical and experimental oncology of gastrointestinal malignancies. His research is focused on the influence of inflammation-induced tumorigenesis and tumor progression in colorectal and pancreatic cancer. In addition, he is interested in the role of cancer stem cells and the development of specific cancer cell-targeted as well as immune cell based-tumor therapies.

Abstract:

Statement of the Problem: Toll like receptor (TLR) signaling has been suggested to play an important role in the inflammatory microenvironment of solid tumors and through this inflammation-mediated tumor growth. Recently we reported about the role of the two intracellularly expressed TLRs, TLR7 and TLR8, in solid tumor growth. Expression of both receptors is upregulated in primary tumors from patients with colon and pancreatic cancer. In both human cancers TLR 7 and 8 expressions was related rather to cancer cells then to tumor-infiltrating immune cells and their expression was associated with tumor cell growth and progression in both tumor entities. Here, we studied the role of tumor cells in their process of self-maintaining TLR expression independent of inflammatory cells and cytokine milieu for auto-regulative tumor growth signaling in pancreatic cancer.

Methodology & Theoretical Orientation: We analyzed the expression of TLR2, TLR4, and TLR9 in primary human cancers obtained from surgically resected patients and the impact of the TLRs on tumor growth via induced activation in several established pancreatic cancers. TLR-stimulated pancreatic cancer cells were specifically investigated for activated signaling pathways of VEGF/PDGF and anti-apoptotic Bcl-xL expression as well as tumor cell growth.

Findings: The primary pancreatic cancer tissues and cell lines expressed TLR 2, 4, and 9. TLR-specific stimulation resulted in activated MAP-kinase signaling, most likely via autoregulative stimulation of demonstrated TLR-induced VEGF and PDGF expression. Moreover, TLR activation prompted the expression of Bcl-xL and has been demonstrated for the first time to induce tumor cell proliferation in pancreatic cancer.

Conclusion & Significance: These findings strongly suggest that pancreatic cancer cells use specific Toll like receptor signaling to promote tumor cell proliferation and emphasize the particular role of TLR2, TLR4, and TLR9 in this autoregulative process of tumor cell activation and proliferation in pancreatic cancer.

Michael Jones

Imperial College, London

Title: The cost of managing severe acute pancreatitis in critical care
Speaker
Biography:

Michael Jones have served on the Editorial Board for the Elsevier journal Travel Medicine and Infectious Diseases 2007 to the present, the International Medicine Committee, Royal College of Physicians of Edinburgh 1996-9, the Scottish Medicines Commission as an Expert Advisor on anti-infectives from 2008 to 2014, the NHS Scotland National Plasma Products Expert Advisory Group 2009-14 and the Scottish Malaria Advisory Group (Health Protection Scotland) 2012-14.

Abstract:

Introduction & Objectives: Acute severe pancreatitis (ASP) leads to organ failure lasting more than 48 hours. ASP patients have prolonged admissions requiring extensive multi-disciplinary input and critical care. This study aims to assess the cost of managing this group of patients in an NHS tertiary referral center. It compares cost per patient vs. payment received, and asks the question of whether transferred patients are more expensive to manage.

Methods: Retrospective study comprising all patients with ASP requiring critical care at a tertiary center between Jan 2014-Aug 2015. Diagnosis coding, length of stay in critical care vs. ward, costs of investigations/interventions, and payments received were obtained using trust coding/finance departments. Radiology investigations/interventions found via local radiology ‘PACS’ system. Blood tests were estimated at £15 and this cost was added to every day of critical care stay, and every other day of a general surgery bed stay.

Results: Out of 30 admissions 29 patients were with ASP. Direct admissions comprised 18 patients admitted via A&E and 1 from clinic. 11 patients were transferred from other trusts. Total payments received were £715,958. Average payment per patient was £23,865 (standard deviation £30,584). Total cost of care was £696, 152. Average age of direct admissions was 55 years, and 47 years for transfers. Mean overall length of stay (LOS) for direct admissions was 30 days, and 47 days for transfers. Mean critical care LOS was 10 days for direct admissions, and 18 days for transfers. Critical care bed days were majority of expenditure at £529,695. Average cost of care for direct admissions was £16,760, and £34,413 for transfers.

Conclusions: Critical care bed days account for the majority of care costs for this group of patients. Care costs are higher for transferred patients but this is offset by a higher rate of payment for receiving trusts. Current payments do seem appropriate. A prospective database is essential for accurate future assessment.

Suh Ching Yang

Taipei Medical University, Taiwan

Title: Impaired homocysteine metabolism in patients with alcoholic liver disease in Taiwan
Speaker
Biography:

S C Yang is a Professor in the School of Nutrition and Health Sciences, Taipei Medical University. She has worked on the relationship between nutrition and alcoholic liver diseases.

Abstract:

Background: Impaired homocysteine metabolism plays an important role in alcoholic liver disease (ALD); however, there are limited data about its relationship with the risk and severity of patients with ALD in Taiwan.

Participants & Methods: To understand plasma homocysteine and related vitamin concentrations in patients with ALD in Taiwan, we recruited 50 male patients with ALD from Cathay General Hospital, with 49 age-and gender-matched healthy adults as the control group. The Institutional Review Board for Human Studies approved the study, and informed consent was obtained from all patients prior to blood collection.

Results: Significantly higher plasma homocysteine concentrations but lower folate concentrations were obtained from patients with ALD. In addition, patients with ALD showed a significant lower erythrocyte reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio but higher plasma thiobarbituric acid-reactive substance (TBARS) concentration, which indicated that oxidative stress was occurring in patients with ALD. A negative correlation between plasma folate and homocysteine was observed in all subjects. There was also a negative correlation between plasma homocysteine and the erythrocyte GSH/GSSG ratio which indicated impaired homocysteine metabolism may have disrupted the antioxidative status. In addition, patients in Child-Pugh class B and C showed higher plasma vitamin B12 concentrations than did patients without cirrhosis and patients in Child-Pugh class A.

Conclusion: These findings show that impaired homocysteine metabolism was observed in patients with ALD in Taiwan. In addition, the plasma vitamin B12 concentration may reflect the degree of liver injury.

Bevin Gangadharan

University of Oxford, UK

Title: Towards the first antibody-free serum biomarker assay for NAFLD
Speaker
Biography:

Dr. Bevin Gangadharan is a research associate in the Oxford Antiviral Drug Discovery Unit, University of Oxford headed by Prof. Nicole Zitzmann (http://zitzmannlab.com/). The main focus of his current research is to use proteomics to identify and validate novel serum biomarker candidates for NAFLD.He carried out his DPhil with Prof. Nicole Zitzmann where he identified serum biomarker candidates for liver fibrosis in hepatitis C patients.

Abstract:

Background
Liver biopsy is the reference standard for NAFLD diagnosis and staging. NAFLD can be assessed less invasively using immunoassays to detect serum biomarkers. However, biomarkers can degrade due to sample storage conditions and therefore may not be detected using these antibody-based assays. Detection of biomarkers by mass spectrometry (MS) overcomes this disadvantage.

Methods

MS and two dimensional gel electrophoresis (2DE) were used to find differences in the abundance of proteins among serum samples from patients with varying NAFLD and fibrosis stages (NAFL, NASH F0, NASH F1, NASH F3 and healthy individuals). The identified proteins are potential NAFLD biomarkers. Mass spectrometry was used to assay for biomarkers by detecting their tryptic peptides and fragments. We are the first and only lab to use a novel quantitation method with clinical samples. Unlike current liver disease biomarker tests, our approach is the only biomarker assay using a universal calibration mix.

Results
Using MS and 2DE, we identified several potential biomarkers for NAFLD which were checked by both targeted MS and Western blotting using serum from patients with varying stages of NAFLD. Our novel biomarkers look promising when compared to cytokeratin-18 and the protein markers used in NashTest. A mass spectrometry assay was developed for the most promising novel liver fibrosis biomarkers.

Quantitation of a novel NAFLD biomarker by MS

Conclusion
We are working towards the first ever antibody-free biomarker assay for NAFLD. Our assay is nine times faster than conventional quantitation by MS making our approach for absolute biomarker quantitation applicable for clinical use. In all current liver disease biomarker assays, different calibrations curves are required for each biomarker with each point on the curves being read separately and samples could be analysed several hours after establishing a calibration curve by which time there is the possibility of instrument drift. Our assay overcomes these disadvantages since it is the only assay which can analyse all points of the calibration curve and determine the absolute concentration of the NAFLD biomarker in a single acquisition. Our assay may help reduce the need for invasive liver biopsies in NAFLD patients.

Speaker
Biography:

Qingyong Ma has completed his PhD from Queen’s University of Belfast during 1992 to 1996. He is the professor and head of Department of Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi’an, China. He has his expertise in pancreatitis and pancreatic cancer. He has published more than 100 papers in reputed journals and has been serving as an editorial board member of repute.

Abstract:

Accumulating evidence has revealed the cancer preventive and therapeutic effects of metformin, one of the most widely prescribed medications for type 2 diabetes mellitus. However, its role in pancreatic cancer is not fully elucidated. Herein, we aimed to further study the preventive and therapeutic effects of metformin in genetically engineered mouse models of pancreatic cancer. We treated KrasLSL-G12D/+; Pdx1-Cre (KC) mice with vehicle or metformin for 4 weeks. Chronic pancreatitis was induced by peritoneal injection of cerulein. KrasLSL-G12D/+; Trp53fl/+; Pdx1-Cre (KPC) mice were used to investigate the therapeutic efficiency of metformin. We found that following metformin treatment, acinar-to-ductal metaplasia (ADM) and mouse pancreatic intraepithelial neoplasia (mPanIN) were decreased in KC mice. Chronic pancreatitis induced a stroma-rich and duct-like structure and increased the formation of ADM and mPanIN lesions, in line with an increased cytokeratin 19 (CK19)-stained area. Metformin treatment diminished chronic pancreatitis-mediated ADM and mPanIN formation. In addition, it alleviated the percent area of Masson’s trichrome staining. In KPC mice, metformin impaired tumor growth and decreased the incidence of abdominal invasion. More importantly, it prolonged the overall survival. In conclusion, we demonstrate that metformin shows promising effects in the prevention of pancreatic tumorigenesis and pancreatic cancer progression.

Speaker
Biography:

Abstract:

Activation of hepatic stellate cells (HSCs) into collagen producing myofibroblasts is critical for pathogenesis of liver fibrosis. Recent studies have shown effect of microRNAs (miRNAs) on regulating HSC activation during liver fibrosis. Here, we aimed to explore the roles of miR-185 in human liver fibrosis. Expression of plasma miR-185 was detected in HBV-related liver fibrosis patients (S2/3, n=10) and the liver cirrhosis patients (n=8) by quantitative real time polymerase chain reaction (qRT-PCR), and healthy volunteers was selected (n=8) as control group. We found that the expression of plasma miR-185 in the HBV-related liver fibrosis patients was significantly downregulated. Carbon tetrachloride (CCl4)-induced mice fibrotic liver tissues and TGF-β1-induced activated HSCs also present down-regulation of miR-185 concomitant with increased expression of RHEB and RICTOR. To analyze the correlation of RHEB and RICTOR expression with miR-185, LX2 cells were transiently transfected with miR-185 mimics, and the expression of α-SMA, collagen â…  and collagen â…¢ was decreased as well as the expression of RHEB and RICTOR. Furthermore, dual-luciferase reporter assays indicated that miR-185 inhibited the expression of RHEB and RICTOR through direct targeting their 3’UTR regions. Moreover, knockdown of RHEB and RICTOR suppressed α-SMA and collagenâ…  and collagen â…¢ in HSCs. In conclusion, miR-185 prevents liver fibrogenesis by inhibiting HSC activation through inhibiting RHEB and RICTOR. These results provide novel mechanistic insights for the anti-fibrotic effect of miR-185.

Speaker
Biography:

Lulu Xu is doing her PhD in Life Sciences from the School of Life Science and Technology, China Pharmaceutical University. Her research work focuses on liver diseases. She has done her Bachelor's degree from China Pharmaceutical University, China.

Abstract:

Liver is an important metabolic organ, which is usually attacked by various toxic substances, such as bacteria, viral hepatitis, alcohol and hepatotoxic drugs. ALF, characterized by a sudden large area of inflammation and extensive hepatocyte death, is defined as a life-threatening disease with a high mortality rate. Although many drugs are commercially available to ALF, there are still no ideal therapeutic methods. Berberine (BBR), an isoquinoline alkaloid extracted from Chinese herb Rhizoma Coptidis, has several pharmacological activities. The study was aimed to investigate the effect of BBR on ALF in vivo and in vitro. Mice were administered intraperitoneally with BBR (5, 10 and 15 mg/kg/d) and orally with silymarin (200 mg/kg/d) for 3 days prior to an injection of D-Galactosamine (D-GalN)/lipopolysaccharide (LPS). The mortality and liver damage were subsequently evaluated. The results showed that BBR attenuated D-GalN/LPS induced liver damage, as evidenced by the reduction of mortality, the alleviation of liver pathological changes and the down-regulation of alanine aminotransferase (ALT)/aspartate aminotransferase (AST). Additionally, BBR exerted anti-oxidant capacity with the rise of hepatic glutathione (GSH) in ALF. The data also exhibited that BBR suppressed D-GalN/LPS induced the nuclear translocation of NF-κB p65 and the expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) at mRNA and protein levels. In vitro, human L02 hepatocytes injury was stimulated by D-GalN (5 mM)/TNF-α (100 ng/ml) and the cell apoptosis was improved by pre-incubation with BBR. Western blotting showed that BBR effectively suppressed apoptosis via modulating bax/bcl-2 rate, cytochrome c release and caspase-3/-9 cleavage. In summary, we concluded that BBR may be a potential strategy for the treatment of ALF. Our findings demonstrated that the hepatoprotective property of BBR was relied on inhibiting inflammation and apoptosis in ALF.

Speaker
Biography:

Mansour Osman Elhaj is a Medical student at the University of Khartoum, Faculty of Medicine. His research work focuses in the treatment of pancreatic cancer to improve the health care of patients.

Abstract:

Statement of the Problem: With an urgency sparked by the realization that by 2030 this tumor type will be the second most deadly cancer in the United States (after lung cancer). The early symptoms of pancreatic cancer are often very vague. They may precede the diagnosis by years and go unrecognized.

 

Materials & Design: A questionnaire-based study appraising responses from three key groups (house-officers, registrars of medicine, registrars of surgery) within three hospitals (National Military Hospital, Soba University Hospital and Khartoum North Teaching Hospital) using cluster sampling technique with hospital units of surgery and medicine taken as a cluster units. The study comprised of 140 physicians.

 

Results: The mean number of new cases seen by the participants is 3 cases during their practice. 83% of the physicians in this study have seen a pancreatic cancer case (PCC) in their practice. 66.4% of the participants scored average knowledge, 26.4% scored good knowledge and only 7.3% of participants scored poor knowledge. In attitude 52.1% of the participants had negative attitude towards pancreatic cancer. In practice results, 73.6% scored average practice (3-6 out of 9) while 18.6% scored poor practice (0-3 out of 9) and only 7.9% scored good practice.

 

Conclusion: Knowledge about pancreatic cancer presentation, risk factors, differential diagnosis, and genetic component is lower among house-officers group compared to the registrars group. And this is consistent with absence of CPD programs. Among all the physicians included in this study half of them had negative attitude and thought that pancreatic cancer is completely incurable. Most physicians were insightfully aware of both the laboratory tests and surgical management of pancreatic cancer, but most of the physicians didn’t know any prevention factors against pancreatic cancer, so it’s reasonable to assume that this gap of knowledge affects counseling.

  • Poster Presentations
Location: Endeavour
Speaker
Biography:

Abstract:

Hepatocellular carcinoma (HCC), which accounts for 85-90% of primary liver cancer, is now the second leading cause of cancer-related mortality worldwide. Here, we reported that aldo-keto reductase family 7A isoform 3 (AKR7A3) is frequently down-regulated in HCC, associating with poor overall survival rate, elevated serum α-fetoprotein (AFP) and poor differentiation of HCC. The promoter region of AKR7A3 was detected to be hypermethylated. Loss of heterozygosity (LOH) was also detected in AKR7A3. Functional assays on both AKR7A3 overexpressed and knockdown cells, including foci formation, colony formation in soft agar, migration, invasion and tumor formation in nude mice, demonstrated the strong tumor suppressive functions of AKR7A3. In addition, treatment of chemotherapy drug cisplatin showed that AKR7A3 sensitizes tumor cells to apoptosis. Mechanistically, Western blot analysis showed that overexpression of AKR7A3 inhibits the activation of ERK, c-Jun and NF-κB. In summary, we found that AKR7A3 functions as a tumor suppressor gene in HCC through attenuating c-Jun, ERK and NF-κB signaling pathways.

Speaker
Biography:

Hyun Woong Lee is a Professor in the Department of Internal Medicine and Division of Gastroenterology and Hepatology at Chung-Ang University Hospital since 2016. He completed his MD from the Yonsei University of Korea in 1997, followed by a residency in internal medicine and a clinical fellowship in hepatology at Chung-Ang University Hospital. He completed his PhD in Medicine from the Yonsei University of Korea in 2008. He was an Assistant and Associate Professor of the Chung-Ang University of Korea from 2008 to 2016, and was a Visiting Scientist at Centers for Disease Control and Prevention, USA, from 2014 to 2015. He is a member of the Korean Association for the Study of the Liver (KASL) and  the Korean Liver Cancer Association (KLCA).

Abstract:

Background & Aim: Interleukin 6(IL-6) has a context-dependent pro- and anti-inflammatory properties. Here we evaluate the impact of IL-6 levels according to the natural history of chronic hepatitis B (CHB) infection.

Methods: Patients (n=71) with hepatitis B virus (HBV) were enrolled between September 2015 and April 2016. For the treatment naïve chronic HBV carries were recruited. We examined serum levels of IL-6, using cytometric bead array. We studied patients with inactive CHB phase (HBV DNA<1,000 copies/ml, anti-HBeAg+ and normal ALT, n=22), immune tolerant phase (HBV DNA>10,000 copies/ml, HBeAg+ and normal ALT, n=36), and immune active phase (elevated ALT and HBV DNA>10,000 copies/ml, n=13).

Results: Serum IL-6 levels in patients with immune active phase were significantly higher than patients with inactive CHB phase (IL-6: 1.815±803.2 vs. 267.3±245.6 pg/mL) (p<0.001). IL-6 levels in patients with immune active phase were significantly higher than patients with immune tolerant phase (IL-6: 1.815±803.2 vs. 620.2±207.8 pg/mL) (p<0.001). Serum IL-6 level was significantly higher in patients with immune active phase compared with immune tolerant phase and inactive CHB phase (Kruskal-Wallis test, p<0.0017).

Conclusions: We found the impact of IL-6 levels to activate immune system as pro-inflammatory properties in patients with CHB infection.

Speaker
Biography:

Abstract:

Background: Lack of information about the disease and administrative difficulties are major obstacles to hepatitis C virus (HCV) treatment among methadone maintenance treatment (MMT) patients.

Methods: HCV seropositive patients treated in the Adelson Clinic rehabilitation center who were abstinent ≥3 months without active psychiatric disorders were invited to a lecture by a Hepatologist on all aspects of HCV disease. During the period of the study, the standard of care for HCV treatment was PEG-RIBA+PI (telaprevir). The participants completed HCV-knowledge and depression questionnaires before and after the lecture and were then referred to evaluation and treatment in the Tel Aviv Medical Center Liver Unit.

Results: Of 80 eligible patients, 48 attended the lecture and following the lecture scored significantly better on knowledge about HCV than the non-attendees. Lecture attendance predicted referral to treatment (Odds ratio (OR)=13 (95% confidence interval (CI) I 3.9-44.9 P<0.0005)). Of the 41 referrals, 21(51.2%) actually presented at the Liver Unit, and had lower depression scores (OR=0.2, 95% CI 0.06-0.9 P=0.03). Despite administrative difficulties, 15 participants (71.4%) started evaluation, 12 (80%) initiated interferon-based antiviral treatment and 9 subjects (75%) achieved SVR (1 did not respond to treatment and 2 stopped due to adverse events). Of the 59 who were not present at the Liver Unit, 14 (23.7%) were followed elsewhere but only one of them (7.1%) started treatment.

Conclusions: Attendance in a single lecture about HCV, improved knowledge and enhanced HCV treatment initiation among MMT patients, but was adversely affected by depression. In MMT patients, interventions aimed to minimize administrative difficulties and to increase knowledge and awareness to the disease, as well as treatment of depression are necessary. These measures might be even more effective at present, when safe and effective IFN-free therapies to eradicate HCV are widely available.

Speaker
Biography:

Dr. Sharma joined the DRG Epidemiology team in Bangalore in 2016. She specializes in developing epidemiological forecasts and has worked on indications related to the field of infectious disease and primary nervous system epidemiology. Her qualifications include an MPH with special focus on Epidemiology from the Post Graduate Institute of Medical Education and Research, India and a bachelor degree in dental surgery. Prior to joining DRG she was a fellow at the National Health Systems Resource Centre. She was also the resident dental surgeon at UCMS, New Delhi.

Abstract:

Introduction: Despite being an international public health challenge, hepatitis has not been prioritized until recently. The WHO estimates 130-150 million people worldwide, living with chronic hepatitis C virus (HCV) infection and the number is increasing despite improved treatment1. In 2016, the WHO released a global health sector strategy on viral hepatitis based on the Sustainable Development Goals 2030 report1. It enlists targets to be achieved with regard to HCV incidence, diagnosis and treatment, taking 2015 as the base year. This analysis aims to understand the global impact of successful achievement of the WHO targets on viremic prevalent cases.

Methods: HCV viremia is defined as the presence of HCV RNA in the serum. A systematic review of published literature was carried out to extract prevalence, incidence, and genotype distribution data for 45 countries, in addition to an analysis of NHANES data2. Extracted estimates were trended to 2015 based on current diagnosis and drug treatment scenarios. When country-specific studies were unavailable, results were extrapolated from studies based in comparable populations. When gender-specific results were unavailable, gender-specific results from other studies were used after making any appropriate adjustments to reflect differences in age-adjusted risk. Percentage changes according to the WHO targets were applied to 2015 to arrive at the number of cases in 2020 and 2030.

Results: Between 2015 and 2030, there is a considerable decrease in the number of prevalent viremic cases modeled according to the WHO targets. In 2020, the viremic prevalence is highest in Africa (1.54) and lowest in North America (0.76). In 2030, the viremic prevalence ranges from 0.15 in North America to 1.0 in Africa.

Speaker
Biography:

Abstract:

Introduction. Up to now hypoglycaemia episodes and yo-yo events remain a problem during insulin therapy in diabetic patient /1/. Last year at this meeting and at WCDT-2016 we have shown that an Apparatus for Diabetes Diagnosis coupled with Complex for Insulin Therapy (ADD-CIT), using differential temperature (Dt) evaluation dynamics as feedback for pump insulin delivery, could be useful in the treatment of acute life threatening alterations of the glucose metabolism due to type 1 diabetes /2, 3/. We hypothesized that Dt, representing energy production and utilization, thus reflecting glucose metabolism, could be a valuable complement to blood glucose measure for monitoring insulin therapy.

 

Objective. If this hypothesis is true, ADD-CIT use could be useful in any glucose metabolism disorders. The aim of the present work was to verify this assertion.

 

Methods. Three groups of patients were considered studied: with type 1 diabetes (DM-1 - 83); with type 2 diabetes (DM-2 – 45); and patients without known diabetes (DM-0 - 66) but presenting a severe pathology causing acute hyperglycaemia difficult to control. The evolution of Dt was also investigated in a group of 10 healthy volunteers

Part of these patients were treated according usual schemas, the other part was treated by ADD-CIT (Tab.1)

Table 1: Patients cohort

Series

DM 1

DM 2

DM 0

Healthy control

ADD-CIT treated

64 (including 50 with kidney insufficiency)

36 (including 18 with heart pathology)

27 (with heart pathology)

10 (observation only)

usual schema

19

9

39 (24 ARCA, 15 with heart pathology)

0

Total

83

45

66

10

After informed consent, the main inclusion criterion was the presence of hyperglycaemia > 11.1 mmol/l (200 mg/dl) at admission (mean values in different groups - 15±3,5mmol/l). Age, sex, BW were comparable. Observation or session duration was up to 8 hours. Usual clinical investigations were provided including glucose blood level measurement every hours (Acutrends strips or gasometer apparatus ADL-90 Flex).

Results. In the ADD-CIT group of patients a glycaemia decrease of 30-40% from its initial value was observed within 2-4 hours and a stable mean glucose level equal or inferior to 11.1 mmol/l was obtained. Rare episodes of hypoglycaemia (< 4,3 mmol/l) and no yo-yo phenomena were observed. In the control groups monitored only by glycaemia evaluation, this result was attained only after 5-7 hours with frequent yo-yo phenomena. Hypoglycaemia events were also present. No correlation was noted between Dt and glycaemia. Dt values were negative mainly in decompensated DM 1 patients. Dt decreased during the sessions in DM 2 patients but rarely reached negative levels. Dt increased at the end of any successful session approaching values observed in healthy controls. This increase was an indication for stopping the session. In some cases Dt abnormally felt at the end of a session whereas glycaemia remained stable: then a caution glucose injection corrected the situation without glycaemia modification.

Discussion and conclusion. Though our series were are small and not fully matched, the results of the ADD-CIT groups of patients in terms of glycaemia decrease and stabilization were convincingly better than in patients treated using the usual procedure based only on glycaemia measurements. This confirms the usefulness of Dt evolution evaluation as a complementary feedback for insulin delivery not only in DM 1 patients but also in DM 2 and any other patients with acute severe glucose metabolism disorders.

Seth Kuranz

Decision Resources Group, USA

Title: The Global Burden of Hepatitis C: A 10-year Forecast
Speaker
Biography:

Mr. Kuranz is an epidemiologist at DRG specializing in the epidemiology of metabolic, renal and psychiatric disorders. He holds an MPH from Boston University.  Prior to joining DRG, he served as the coordinator of an international research project focusing on early adult development and substance abuse dependence.

Abstract:

Introduction: Hepatitis C virus (HCV) contributes substantially to the burden of disease worldwide. Modes of transmission and risk of HCV differ by geographic regions (WHO, 2016). The impact of HCV treatment on the future prevalence and incidence of HCV will vary based on rates of diagnosis and compliance.

Methods: To estimate the incidence and prevalence of HCV, we systematically reviewed the literature (DRG, 2017) and analyzed NHANES cycles 2007-2014 (CDC, 2016). We defined prevalent anti-body positive cases of HCV as individuals who received a positive result on an ELISA or equivalent test and, where possible, in combination with a RIBA. We defined HCV viremia as the presence of HCV RNA in the serum. We incorporated diagnosis and drug-treatment assumptions into out trend and these were applied to region-specific HCV genotype (Gower E, 2014) and cirrhotic distributions. The 10-year forecast incorporated demographic changes related to aging and population growth. When country-specific data were unavailable we extrapolated based on data from comparable countries. To estimate the number cases in each country, we multiplied the age- and gender-specific estimates presented in these studies by the UN population estimates for each forecast year (United Nations, 2016).

Results: Over the 10-year forecast, incident cases, prevalent anti-body positive cases, and viremic prevalent cases decreased substantially due to reduced risk in the population and improved treatment.  If rates of treatment and treatment efficacy were to remain constant over the forecast period, viremic HCV decreases by over 20% between 2017 and 2027. Assuming treatment becomes more readily available during the forecast period across all regions and that compliance remains relatively high, HCV will decrease to an even greater magnitude by 2027.

Conclusion: Viremic prevalence will decrease substantially in both higher-income and lower-income countries with the later experiencing the largest decrease in prevalence over the forecast period.

Speaker
Biography:

Abstract:

Chronic viral hepatitis (CVH) is the most important risk factor for hepatocellular carcinoma (HCC) and chronic liver disease. The most common two causes of CVH are hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. There are high prevalence of HBV and HCV infection in Taiwan, and the government introduced a national plan of anti-viral treatment (AVT) for HBV and HCV infection since October 2003 but its effect was still not clear.

Aims: To evaluate the effects of the national AVT plan to hospitalization due to HBV and HCV related liver diseases and HCC.

Methods: We used the data base of year 2001 to 2010 from National Health Insurance Administration (NHIA) of Taiwan to calculate the yearly hospitalization amount , mean hospital stay and mean age of hospitalized patients due to acute hepatitis B (AHB) and C (AHC) with or without hepatic coma (ICD-9 codes: 07020, 07030 and 07041, 07051), Chronic hepatitis B (CHB) and C (CHC) with or without hepatic coma (ICD-9 code 07022, 07032 and 07044, 07054) and CHB, CHC related HCC (ICD-9 code 07022,07032 +1550 and 07044,07054+1550). Linear regression was used to analyze the relationship between these hospitalization data and duration of AVT plan.

Results: Data of 982352 random peoples and 734973 of hospitalization during 2004 till 2010 were investigated and showed the yearly hospitalization amount due to AHB in this sample has increased from 368 to 1022 since 2004 to 2010 and mean age of hospitalized patients has increased from 44.9 to 56.2 years old. Hospitalization amount due to AHC, CHB, CHC, CHB with HCC and CHC with HCC also have increased from 366 to 965, 226 to 1066, 230 to 895, 33 to 347 and 22 to 283 respectively, and mean age of them have increased from 54.5 to 62.0, 45.4 to 54.5, 55.3 to 63.5, 55.1 to 60.0 and 66.1 to 69.4 years old respectively.  All above increasing data showed positive linear relationships with the duration of AVT plan ( P < 0.05). However, there was not a linear relationship between the mean hospital stay and the duration of AVT plan.

Conclusions: Hospitalization amount and mean age of hospitalized patients due to HBV and HCV related liver diseases revealed an increased trend during the first 7 years when a national AVT plan was launched in Taiwan. Although many influential factors should be considered such as an increased medical accessibility or aging populations, a longer and more detailed investigation may be necessary to elucidate the benefits of this plan.