Scientific Program

Day 1

KEYNOTE SPEAKERS
  • Lower GI bleeding in patients with cirrhosis

    Columbia University College of Physicians and Surgeons
    USA
    Biography

    Maxwell M. Chait completed his MD degree at the age of 25 from the University of California School of Medicine at San Francisco. He is a Fellow of several prestigious organizations, including the American College of Physicians, American College of Gastroenterology, American Gastroenterological Association and the American Society for Gastrointestinal Endoscopy. He is a practicing gastroenterologist on the faculty of the Columbia University College of Physicians and Surgeons. He has authored numerous publications and serves on the editorial board of the World Journal of Gastrointestinal Endoscopy and the Journal of Liver Disease and Transplantation Biology.

    Abstract

    Lower GI bleeding in patients with cirrhosis

  • Symbiotic bacteria provide chemoprevention against hepatitis B virus mediated hepatocellular carcinoma in hepatitis B x transgenic mice

    Temple Univeristy
    USA
    Biography

    Mark Feitelson received his Ph.D. in Microbiology and Immunology in 1979 from the UCLA School of Medicine. He was an American Cancer Society postdoctoral fellow at Stanford University from 1980-82, and was then recruited to the Fox Chase Cancer Center by Dr. Baruch Blumberg (Nobel laureate). In 1991, Dr. Feitelson became Associate Professor of Pathology and Cell Biology and head of the Molecular Diagnostics Lab in Microbiology at Thomas Jefferson University. In 2007, Dr. Feitelson moved to Temple University, where he is now Professor of Biology. His research has been supported by NIH, industry and foundations for more than 35 years, has more than 140 publications, and is presently head of the Professional Science Master’s program in Biotechnology at Temple University. Since 1980, his research interests have encompassed the pathogenesis of chronic hepatitis B infection and development of hepatocellular carcinoma on the cell and molecular levels.

    Abstract

    Chronic infection with hepatitis B virus (HBV) is associated with the development of progression of chronic liver disease (CLD) and the appearance of hepatocellular carcinoma (HCC). HCC is a prevalent cancer worldwide with few treatment options. Given that HCC develops most often on the background of chronic inflammation, experiments were designed to test the hypothesis that selected probiotic bacteria that suppress inflammation could be used as a simple and inexpensive means to prevent or delay the appearance of HCC. To test this, hepatitis B x (HBx) transgenic mice, which develop progressive liver lesions that culminate in HCC, were treated with a mixture of probiotic bacteria (Synbiotic 2000) several months prior to the development of dysplasia and HCC. The results showed a significant reduction in the number and size of dysplastic and HCC nodules compared to control transgenic mice. Microarray analysis of selected immune and cancer associated markers showed a strong reduced expression in the liver of mice treated with Synbiotic 2000 compared to controls. Thus, Synbiotic 2000 attenuates the pathogenesis of HCC, and may be useful in cancer chemoprevention, not only for HCC, but perhaps against other cancers that often develop on the background of chronic inflammation.

  • Hepatitis C Virus (HCV) Infection: A GLOBAL EPIDEMIOLOGY UP-DATE OF THE CIRCULATION OF HCV GENOTYPES

    National Cancer Institute
    Italy
    Biography

    Arnolfo Petruzziello was born in Naples (Italy) where he is the Head of the Virology and Molecular Biology Unit of National Cancer Institute, IRCCS Fondazione G. Pascale in Naples, Italy. Post degreed in Microbiology and Virology and PhD in Molecular and Cellular Pathology, after having completed his post doctoral studies at University Federico II of Naples, he has published numerous research papers in peer-reviewed international journals and has extended his valuable service towards the scientific community with his extensive research work. He is also Rewiever and Editorial Board member for several international scientific journal and Conferences.

    Abstract

    Hepatitis C virus (HCV) is one of the major globally prevalent pathogen and one of the main leading cause of death and morbidity . The last estimates of disease burden showed an increase in seroprevalence over the last 15 years to 2.8%, equating to >185 million infections worldwide.
    Persistent HCV infection is associated with the development of liver cirrhosis, hepatocellular cancer, liver failure and death and is basically the most common cause of death in HIV-positive patients on highly active antiretroviral therapy .
    Previous and more recent studies have reported regional level prevalence estimates, but always considering a limited number of countries. This study represent one of the most comprehensive effort to quantify global HCV epidemiology, using the best available published data between 2000 and 2015 from 138 countries (about 90% of the global population),grouped in 20 geographical areas (with the exclusion of Oceania), as defined by the Global Burden of Diseases project (GBD).
    Total global HCV prevalence is estimated at 2.5% (177,5 millions of HCV infected adults), ranging from 2.9% in Africa and 1.3% in Americas, with a global viraemic rate of 67% (118.9 millions of HCV RNA positive cases), varying from 64.4% in Asia to 74,8% in Australasia.
    HCV genotype 1 is the most prevalent worldwide (49.1.%), followed by genotype 3 (17.9%), 4 (16.8%) and 2 (11.0%). Genotypes 5 and 6 are responsible for the remaining < 5%. While genotypes 1 and 3 are common worldwide, the largest proportion of genotypes 4 and 5 is in lower-income countries.
    A more precise knowledge of HCV genotype distribution will be helpful to best inform national healthcare models to improve access to new treatments.

  • HCV Outcome Insights from Long-term Cohort Studies

    Rutgers New Jersey Medical School
    USA
    Biography

    Professional awards include the Wade Hampton Frost Lectureship award from the Epidemiology Section of the American Public Health Association (2015), the NJ Public Health Association’s (NJPHA) highest award – the Dennis J. Sullivan Award (2012), the NJPHA Dr. Ezra Mundy Hunt Award (2007), the first recipient of the American Lung Association of NJ’s “CAREforAIRnj Award for Community Outreach/Action/Advocacy, the “Cancer Liaison Physician Outstanding Performance Award” from the Commission on Cancer of the American College of Surgeons (2010), the Prostate Net’s “In the Know” National Award (2007), the UMDNJ School of Public Health “Faculty Community Service Award”(2007), and the first of the American Society of Clinical Oncology “Travel Awards” for outstanding work (1985). At NJMS, he was elected to membership in Sigma Xi chapter (1992) and as a Faculty member to the Alpha Omega Alpha [¿O¿] Honor Medical Society, Beta Chapter (inducted 2003). For the latter, he has served as an officer as the Assistant Secretary/Treasurer since 2006, and helped to develop its Research Award, the first award of its nature in the US. Dr Stanley H. Weiss graduated from Yale (1974, BA, summa cum laude and Phi Beta Kappa) and Harvard Medical School (1978, MD). He did a residency in Internal Medicine at Montefiore in the Bronx, and fellowships at the National Cancer Institute in Medical Oncology and in Epidemiology.

    Abstract

    HCV Outcome Insights from Long-term Cohort Studies

  • Neontal Biliary Atresia

    National Liver Institute
    Egypt
    Biography

    I am a Professor of Pediatric Nutrition, Gastroenterology and Hepatology. I received my MBBCh, MS, MD and PH.D. from Egypt and USA. I am currently the president of Middle Eastern Association of Nutrition (MENANA), and president of the Egyptian and PanArab Societies of Gastroenterology, Hepatology and Nutrition (EGSPGHAN and PASPGHAN).

    Abstract

    Neontal Biliary Atresia

Liver Transplantation and Liver Surgery ( experimental & clinical)
Speaker
  • Transplantation of bioengineered functional liver surrogates
    Speaker
    Fanwei Meng
    King Faisal Specialist Hospital and Research Center
    Saudi Arabia
    Biography

    Dr. Fanwei Meng completed his Ph.D in 2012 from the Department of Biomedical Engineering at the University of Utah. He later on conducted his postdoctoral trainings at the McGowan Institute of Regenerative Medicine at the University of Pittsburgh Medical Center as well as the University of Texas Medical Center. His research focuses on cell-derived biomaterials as well as biologic scaffold based regenerative approach. He has published more than 10 papers in reputed journals. He is currently an associate scientist at the Organ Transplantation Center of the King Faisal Specialist Hospital and Research Center at Saudi Arabia.

    Abstract

    The shortage of eligible liver donors results in deaths of patients waiting for liver transplantation. It is imperative to identify alternative treatments to bridge the gap. Decellularized liver scaffold based liver regeneration is a promising approach to develop functional liver surrogates. In the current study, decellularized rat liver scaffolds were recellularized with human liver carcinoma cells (HepG2) and re-endothelialized with rat sinusoidal endothelial cells. Decellularized liver scaffolds that were only recellularized with HepG2 were served as the control group. In vitro, the liver scaffolds, that were repopulated with both HepG2 and endothelial cells, were found to upregulate hepatic cell specific genes and perform superior hepatic functions when compared to the counterparts that were only repopulated with HepG2. Recellularized liver scaffolds were under perfusion culture for 7 days and then transplanted to recipient rats heterotopically. The vasculatures of the bioengineered liver grafts remained patent for at least 14 days posttransplantation as demonstrated by the ultrasound imaging. Moreover, Doppler ultrasound observed blood flow patterns similar in characteristics of the arterial and venous flows, respectively, in the bioengineered liver grafts. Functionally, the hepatic P450 metabolic activities and the human albumin production were both detected in the bioengineered liver grafts 14 days post-transplantation. Our results strengthened the feasibility of engineering functional liver surrogates utilizing decellularized liver scaffolds.

  • Will update it soon.
    Speaker
    Sanjiv Saigal
    Medanta Institute of Liver Transplantation and Regenerative Medicine
    India
    Biography

    Dr. Sanjiv Saigal has worked for over 15 years in the field of liver transplantation and has been instrumental in establishing the field of Liver Transplantation in India. He has spearheaded the Medical Team of liver transplantation in the largest liver transplant program in this country for over a decade now. Since his work in liver transplantation at the King's College Hospital, London over a decade back, he has now an experience in dealing with more than 1500 liver transplants, including both cadaver and living donor liver transplants. He is presently the Director and Head of Transplant Hepatology at Medanta The Medicity, Gurgaon which is the busiest Transplant Hepatology Unit in India performing about 25 liver transplants every month with a success rate of over 90%. Besides clinical work, he has a keen interest in academics and research and has numerous publications in leading peer-review journals. He is a life member of various liver societies and has over 130 presentations in National and International forums to his credit. He has received numerous awards including the Calcutta University Gold Medal, National Pfizer Medical award, INLAKS Foundation Fellowship in liver transplantation etc. He is a member of Royal College of Physicians (MRCP) and Member National Academy of medical Sciences (MAMS).

    Abstract

    Will update it soon.

Liver Cancer
Speaker
  • Fibrolamellar-type hepatocellular carcinoma: A histologically unique tumor with a distinctive molecular alteration
    Speaker
    Yue Xue
    Emory University
    USA
    Biography

    Yue Xue has completed MD/PhD training, followed by anatomic and clinical pathology residency at Dartmouth-Hitchcock Medical Center. She later did two fellowships, one in oncologic surgical pathology at Memorial Sloan-Kettering Cancer Center, and the other on gastrointestinal/liver pathology at Emory University. She is an assistant professor at Emory University, where the liver transplant program was ranked second nationally in 2017. As a junior faculty, she has published almost 20 original observations and written 3 book chapters, and been actively involving in pancreatobiliary/liver research.

    Abstract

    Fibrolamellar hepatocellular carcinoma is generally a fairly rare event in routine pathology practice. It is a unique type of hepatocellular carcinoma with a distinctive predilection for young patients without underlying liver disease unlike most hepatocellular carcinomas which arise in the background of liver injury such as hepatitis or cirrhosis. It has a characteristic cell type composed of large polygonal hepatocytes with eosinophilic and granular cytoplasm surrounded by abundant, thick fibrous tissue arranged in lamellar bands of collagen fibers, co-expression of cytokeratin 7 and CD68 and activation of protein kinase A (most often by formation of DNAJB1-PRKACA). In this talk, the distinctive clinic-pathologic features of fibrolamellar hepatocellular carcinoma and the diagnostic pathologic criteria will be reviewed in detail. Further, updated molecular genetics and associated signaling transduction pathway involved with this specific tumor will be particularly highlighted as a primer for anatomic pathologists.

  • TM4SF5 drives aggravation from nonalcoholic fatty to fibrotic and cancerous liver
    Speaker
    Jung Weon Lee
    Seoul National University
    South Korea
    Biography

    JW LEE has completed his PhD from University of North Carolina at Chapel Hill, NC, USA and postdoctoral studies from MSKCC at NY. These days, his research group mostly focuses on the roles of a tetraspanin, TM4SF5, in NASH, fibrosis, tumorigenesis and metastasis, and on the anti-TM4SF5 reagents to block TM4SF5-mediated liver diseases, in either 2D or extracellular matrix-surrounded 3D culture conditions via biochemical, cell biological and molecular biological approaches in addition to animal models, and clinical samples for the fibrotic and tumor models or patients (Lab homepage: http://www.snupharm.ac.kr/jwl/). He has published more than 100 papers in reputed journals.

    Abstract

    Chronic liver injury can lead to inflammation, fibrosis, cirrhosis, and tumorigenesis. Since TM4SF5, a tetraspan(in) with 4 transmembrane domains, is shown to be involved in liver fibrosis, it is reasonable to consider that TM4SF5 can play roles in important roles development of liver diseases. In CCl4-administrated animal livers, the pattern of TM4SF5 expression along the fibrotic septa was in parallel to those of TGF?1, ?-SMA, and collagen I deposition. TM4SF5 is induced by signaling activities of TGF?1- and EGFR-mediated signaling pathways. Therefore, in this current study, we further explored how TM4SF5 is involved in development of liver fibrosis and HCC, using in vitro cell and in vivo animal systems in addition to human tissues. Primary hepatocytes isolated from mice treated with CCl4 for 4 or 16 weeks, to mimic fibrotic and cirrhotic livers, respectively, showed enhanced TM4SF5, ?-SMA, collagen I, and laminins expression, in addition to increased c-Src and STAT3 activities. Suppression or inhibition of TM4SF5, c-Src, or STAT3 could result in blocking of collagen I and laminin expression. Furthermore, when CCl4 administration was performed together with IP or intratumoral treatment of anti-TM4SF5 antibody, the mice showed reduced development of CCl4-mediated fibrosis phenotypes in livers and tumor formation by xenografts, in addition to reduced STAT3 signaling activity and ECM deposition. These observations suggest that TM4SF5 may be involved in the development of fibrosis and tumorigenesis, via its roles in ECM induction through c-Src and STAT signaling pathways.

  • A subtle increase in wild-type RTK levels provides a permissive context allowing multiple signaling cooperators to initiate liver cancer
    Speaker
    Flavio Maina
    IBDML (Developmental Biology Institute of Marseille-Luminy)
    France
    Biography

    Flavio Maina has completed his PhD at the University of Turin (Italy) and postdoctoral studies at EMBL (Germany). He is group leader at the IBDM since 2000. He was recruited at the CNRS as CR1 in 2000, got the HDR in 2005, then promoted DR2 in 2010 and DR1 in 2015. He has published more than 50 papers in reputed journals. His team studies how qualitative and/or quantitative receptor tyrosine kinase (RTK) signaling changes lead to diversified cell behaviors. By applying integrative approaches, the team explores vulnerability versus resilience of cells to signaling fluctuations, and how cell plasticity intercalates such signaling changes. Most of team projects are based on interdisciplinary approaches. Strong scientific team competences include those on: RTK signaling, cell signaling mechanisms, mouse genetics and development, gene targeting, stem cell biology, and liver cancer. Research is performed by intercalating phenotypic and mechanistic studies in cultured cells and in vivo.

    Abstract

    Aberrant receptor tyrosine kinase (RTK) signaling is essential during liver cancer evolution and resistance to therapies. Using mouse genetics, we recently demonstrated that a subtle increase of wild-type RTK levels leads to cancer in sensitive tissues, illustrating how the shift towards cancerogenesis can stem from a slight perturbation of signaling dosage. In particular, when the Met RTK is slightly enhanced in liver, mice (namely Alb-R26Met) spontaneously develop hepatocellular carcinoma (HCC), which belong to the so called “proliferative progenitors” subclass (Fan et al. Hepatology 2017 Nov;66(5):1644-1661).
    To uncover new genes that cooperate with RTKs during tumor initiation, we combined the clinically-relevant Alb-R26Met mice with the Sleeping Beauty (SB) transposon (T2/onc) mutagenesis system. Whereas neither Alb-R26Met nor T2/onc-Alb-R26SB/+ mice developed tumors at 30 weeks of age, T2/onc-Alb-R26SB/Met mice (with enhanced Met in liver in addition to active SB-driven mutagenesis) developed multiple liver tumors, each carrying distinct genomic insertions. Analysis of 251 independent tumors led to the identification of 285 putative cancer-related genes: some of them correspond to known proto-oncogenes or tumor suppressors, thus validating the overall strategy we employed for cancer gene discovery; other genes have not previously linked to cancer. Integrative analysis with human data revealed that a large proportion of identified genes are also altered in HCC patients. Moreover, we compared our screen outcomes with those performed in other tumor-sensitizing contexts and found 71 genes that emerged specifically in our RTK-sensitized background. In vivo assays established the functional relevance of several new putative tumor suppressors.
    Overall, our screen strategy identifies new functional mechanisms destabilizing liver homeostasis and illustrates how a subtle increase in wild-type RTK levels provides a permissive context for several types of cooperative mechanisms leading to liver tumor initiation.

Liver fibrosis
Other Liver Diseases
Speaker
Liver Imaging modalities
Speaker
  • 1
    Intraductal ultrasonography as a local assessment before magnetic compression anastomosis for obstructed choledocho-jejunostomy
    Speaker
    Hideaki Kawabata
    Kyoto Okamoto Memorial Hospital
    Japan
    Biography

    Dr. Hideaki Kawabata is a clinical gastroenterologist to the core and now Director of the Department of Kyoto Okamoto Memorial Hospital, Head of the Gastroenterological Center and Chief of the Palliative Care Team at our hospital, as well as a Specialist and Councilor in the Japanese Society of Gastroenterology and the Japan Gastroenterological Endoscopy Society and a Specialist in the Japanese Society of Internal Medicine and the Japanese Society of Gastrointestinal Cancer Screening.

    Abstract

    Magnetic compression anastomosis (MCA) has been developed as a non-surgical alternative treatment for biliary obstruction, however, the precise assessment of the local condition is still difficult. Intraductal ultrasonography (IDUS) provides real-time, high-quality, cross-sectional images of the bile duct and periductal structures. A 70-year-old woman who had undergone pancreaticoduodenectomy for pancreatic head cancer suffered from obstructed choledocho-jejunostomy with no recurrent findings. Cholangiography using the percutaneous transhepatic cholangiographic drainage (PTCD) and fluoroscopy revealed complete obstruction of the upper common bile duct, and the distance of the obstruction was 7 mm. IDUS showed fibrous heterogenous hyperechoic appearance without fluid collection, vessels or foreign bodies at the site of the obstruction. We performed choledocho-jejunostomy using the MCA technique. One magnet was inserted into the obstruction of the hepatic side through the PTCD fistula. Another was delivered endoscopically to the obstruction of the jejunal side. The two magnets were immediately attracted towards each other transmurally, and reanastomosis was confirmed 7 days after starting the compression. The magnets were easily retrieved endoscopically. A 16-Fr indwelling drainage tube was placed in the juodenum through the PTCD. The internal tube removed twelve months after reanastomosis, and no MCA-related complications have been observed. In conclusion, MCA is a safe, effective, low-invasive treatment for biliary obstruction, and IDUS is useful for the pretreatment assessment of feasibility and safety.

  • Totally Laparoscopic Caudate Hepatectomy for Cancer
    Speaker
    Zhe-Ping Fang
    Wenzhou Medical University
    China
    Abstract

    Background: In the past 15 years, we have completed more than 560 cases of laparoscopic hepatectomy, there are two cases of caudate lobe. Caudate hepatectomy remains a surgical challenge in spite of recent advances in laparoscopic technique. Hepatic tumor in the caudate lobe is usually deeply located in the center of the liver and close to the vena cava and hepatic hilum. Thus, lesion in this region was considered as a contraindication of laparoscopic hepatectomy. The aim of this study is to explore the safety and feasibility of laparoscopic hepatectomy for lesions in the caudate lobe.
    Methods: Two patients with caudate hepatic tumor received laparoscopic caudate hepatectomy in our hospital from Nov. 2016 to July 2017.
    Results:All procedure for two patients with caudate hepatic tumors (sizes 2.5, 4.5cm) were completed with totally laparoscopic technique. The average operative time was 268 min. and estimated blood loss was 180 ml, and average length of postoperative hospital stay was 7.5 days. There was no perioperative complications and patient mortality.
    Conclusions: Our experience demonstrated that laparoscopic hepatectomy is a safe and feasible procedure for caudate hepatic tumors in selected patients.

  • Robotic liver resections –My experience
    Speaker
    Sanjay Goja
    Medanta Institute of Liver Transplantation and Regenerative Medicine
    India
    Biography

    After completing general surgical residency, got further training in surgical gastroenterology, HPB and Liver transplantation for three years followed by clinical fellowship in Liver transplantation. Have been working as senior consultant HPB and liver transplant surgeon with experience of nearly 2000 liver transplants, including both deceased and live donor. Have done more than thousand live donor hepatectomies and many complex liver resections involving vascular reconstructions. Also leading minimal access HPB surgery in the unit presently working. Did first Robotic hepatectomy in India. Published first case report and first series of robotic liver surgery from India. Am European Board certified(UEMS) in liver transplantation. Have authored (first or co author) many publications. My recent publication being Right Lobe Donor Hepatectomy, Is it safe? In Transplant International Journal. My areas of interest are safety of living donor hepatectomy, machine organ perfusion, Robotic liver surgery and complex liver resections.

    Abstract

    Background: The authors present their experience of robotic liver resections in comparison with open surgery.
    Methods: Retrospective review of liver resections done robotically from February 2015 to Octuber 2017 compared to cohort of open cases from January 2012 to December 2016.
    Results: Nineteen patients in the study group were compared with matched control of 38 open cases. Mean operative duration was 442 ± 135 minutes in the robotic compared to 357 ± 127 minutes in control group (p = 0.03). Mean blood loss was 270 ± 311 ml in the robotic compared to 451 ± 330 ml in control group (p = 0.06). Minor complications developed in 17% of robotic cases compared to 41% in open surgery (p = 0.5), while major complications occurred in 5.8% of robotic cases compared to 8.8% of open (p = 0.3). Mean hospital stay was 5.35 ± 0.8 days for the robotic group and 7.7 ± 4.2 days for open group (p = 0.02).
    Conclusion: This study highlights the utility of robotics for liver resections with better outcomes and decreased length of stay compared to open surgery albeit at a higher cost at present.

  • Two Incisions Laparoscopic Cholecystectomy: a Simple Way to reduce scar
    Speaker
    Rafael Antoniazzi Abaid
    University of Santa Cruz do Sul
    Brazil
    Biography

    Rafael Abaid has completed his PhD at Digestive Surgery Division, Department of Gastroenterology, University of Sao Paulo School of Medicine, USP, Brazil and is Professor in Medicine School, University of Santa Cruz do Sul, UNISC, Brazil

    Abstract


    About 20% of the population has cholelithiasis and this is the main abdominal cause of hospitalization in developed countries. Considering that only in the United States about 700,000 cholecystectomies are done each year, it is possible to estimate the importance of the problem for public health.

    For a century, since Carl Langenbuch removed the first gallbladder, cholecystectomy was only performed through laparotomies. In the 1980s, laparoscopic cholecystectomy (LC) appeared. The technique was improved and spread rapidly in the 1990s. It is one of the most frequently performed procedures today and is still considered gold standard technique in the treatment of symptomatic cholelithiasis. Although large and traumatic incisions have been replaced by four small 5-mm and 10-mm incisions, many surgeons continue to search for even less invasive techniques. The reduction of surgical trauma has potential benefit of causing less postoperative pain, reducing convalescence time and generating better aesthetic results. Several techniques have been described with these objectives. As LC is a relatively inexpensive and easy-to-perform technique, the greatest challenges are to maintain safety without increasing technical difficulty or cost.

    In accordance with safety standards and with the intention of reducing scars, it was proposed to perform two incisions simplified laparoscopic cholecystectomy using a hybrid technique with an incision inside the umbilicus and another in the epigastrium to operate similarly to standard LC.

Liver Inflammation and Immunology
Speaker
Molecular and cellular biology
Speaker
  • Mesenchymal stem cell derived Hepatocytes (iMHeps): Invaluable tools for predictive hepatotoxicity and immune-compatible surrogates for liver function support
    Speaker
    S Jyothi Prasanna
    Manipal University
    India
    Abstract

    Scarcity of liver donors and difficulties in obtaining functional primary human hepatocytes in clinically relevant numbers poses immense challenge for liver transplantation. This extrapolates to non-availability of primary hepatocyte culture alternatives for drug induced hepatotoxicity screening and studying hepatotropic infections. Though iPSC-derived hepatocyte cells emerged as alternatives, maturity of the differentiated state, prominence of fetal metabolism, promiscuous differentiation to related endoderm lineages and immune rejection poses a roadblock for preclinical/clinical applications. Owing to ease of expansion and established immune-evasiveness of Mesenchymal stem cells (MSCs), an attempt is made to trans-differentiate human adipose tissue derived MSCs to hepatocytes using a combination of developmentally relevant transcriptional factors and hepatogenic cues. iMHeps so derived manifested robust expression of liver enriched transcription factors, metabolic signatures comparable to human hepatocytes, drug inducible Cytochrome P450 enzyme activities mirroring adult hepatocytes and robust xenobiotic clearance. iMHeps are permissive to hepatotropic viruses certifying junctional maturity, a facet required for viral entry. In-depth analysis of background mesenchymal memory in iMHeps indicated erasure of connective tissue differentiation potential indicating stability of the hepatic state even upon withdrawal of the initial hepatogenic cues used for trans-differentiation. Though iMHeps have forgone Mesenchymal differentiation abilities an unanticipated conservation of immune-modulatory abilities, a hallmark of native MSCs, was exhibited by iMHeps upon co-culture with activated immune cells. iMHeps could thus emerge as immune-compatible alternatives to primary human hepatocytes and transformed hepatoma lines for studies on drug induced hepatotoxicity, modelling liver infections and as transplantable surrogates for liver failure.

  • HGF/R-spondin1 rescues liver dysfunction through the induction of Lgr5+ liver stem cells
    Speaker
    Zhou Weijie
    Southern Medical University
    China
    Biography

    Zhou Weijie, 2003 by the Shandong University of Life Sciences bachelor's degree in 2010 in Shanghai Institute of Biochemistry and Cell obtain Doctor degree, 2011-2015 years postdoctoral fellow in the Department of Biomaterials, University of Michigan, 2015 returning home has served as the basis of Southern Medical University Department of Pathology Professor, Ph.D. It was supported by Outstanding Youth Fund of Guangdong Province in 2015 and selected as the twelfth batch of National Youth Thousands Program. Published first author or correspondence author papers in Nature , Cell Research , Oncotarget and others. Proposed a new scheme of adult stem cell induction and radiotherapy and chemotherapy combined treatment of cancer. Mainly engaged in the mechanism of tumor and treatment research and stem cell repair and regeneration of tissue injury mechanism and application research.

    Abstract

    The induction of endogenous adult stem cells by administering soluble molecules provides an advantageous approach for tissue damage repair, which could be a clinically applicable and cost-effective alternative to transplantation of embryonic or pluripotent stem cell-derived tissues for the treatment of acute organ failures. Here we show that HGF/Rspo1 induce liver stem cells to rescue liver dysfunction. Carbon tetrachloride treatment causes both fibrosis and Lgr5+ liver stem cell proliferation, whereas Lgr5 knockdown worsens fibrosis. The Injection of HGF in combination with Rspo1 increases the number Lgr5+ liver stem cells and improves liver function by attenuating fibrosis. We observed Lgr5+ liver stem cells in human liver fibrosis tissues, and once isolated these cells were able to form organoids, treatment with HGF/Rspo1 promoted their expansion. We suggest that Lgr5+ liver stem cells represent a valuable target for liver damage treatment and that HGF/Rspo1 can be used to promote liver stem cell expansion.

  • Stem cells and Liver regeneration
    Speaker
    Balasundari Ramesh
    Apollo Cancer Institute
    India
    Biography

    Dr.Balasundari Ramesh, Scientist from Apollo hospital, Chennai. Had completed her Master degree in Microbiology and PhD in biomedical science under MAHER University, India. Her PhD thesis was involved in differentiation of human Mesenchymal stem cells to precursor cardiomyocytes using ischemic heart conditioned media. In her previous institution, Frontier Lifeline Pvt ltd she was involved in Stem cells clinical trial for cardiac patients (Myocardial infarction, Cardiomyopathy) and Critical limb ischemia. She was also involved in various translational researches such as tissue engineering of xenografts, biological wound dressing, production and preservation of RBCs from hematopoietic stem cells. Had published more than 10 articles in peer reviewed international and national journals. Involved in 2 govt of Indian projects as principal investigator and 3 co-investigated projects

    Abstract

Drug Induced Liver Injury (DILI)
Speaker
  • THE RESULT OF CLINICAL TRIAL FOR THE NEW LONAL DRUG FOR HEPATOPROTECTIVE EFFECT IN PATIENT WITH DRUG INDUCED STEATOSIS: A Randomized Placebo-Controlled Double Blind Clinical Trail
    Speaker
    Ariunaa Zundui
    Treatment, Research and Production Company of The Mong-Em
    Mongolia
    Abstract

    The aim of the our clinical trial was to determine hepatoprotective effect of the new Lonal drug in patient with drug induced steatosis. The research was considered such as clinical trial guideline for new drug issued by the World Health Organization’s "Good Clinical Practice”. Based on permission given by Biomedical Ethical Community of the Health Ministry of Mongolia approved diagnosis patient with drug induced steatosis. The our research design is Randomized Placebo-Controlled, Double Blind Clinical Trial. Lonal drug significant decreases hepatocellular and cholestatic injury. The Lonal drug was taken during 21 days and comparing the some results of metabolic syndrome before and after treatment, reduces TG (p=0,03). The participants have taken the fibroscan and liver biopsy. That was compared to determine before and after treatment such as steatosis and fibrosis degree of participants liver. Before treatment degree of steatosis was S3, after treatment it was dropped S2 (p <0.05). And before treatment, such as fibrosis degree F1-2, after treatment it was decreased F0 (p<0.05). New Lonal drug is reducing hepatocellular injury, cholestatic injury and some criteria of the metabolic syndrome in patient drug induced steatosis. Also new Lonal drug reduces activition of inflammation, decreases the degree of liver steatosis fibrosis validated by liver biopsy and fibroscan.

Video Presentations
Speaker
  • The management of functional constipation
    Speaker
    Antonio Iannetti
    Sapienza University of Rome
    Italy
    Biography

    Degree in Medicine and Surgery and Specialties in "Gastroenterology" and "Internal Medicine" at the University of Rome. 1980-1983 University of Los Angeles (USA), he is interested endoscopic sclerosis of esophageal varices and retrograde cholangiopancreatography-endoscopically. University Professor - Chair of Gastroenterology - University of Rome. Head of the Digestive Endoscopy Service of the University Hospital Umberto I in Rome. Professor of "Endoscopy" and "Digestive System Diseases" at the Faculty of Medicine, University of Rome - "La Sapienza." Lecturer in E.C.M. Courses (Continuing Medical Education), national and international. Expert of the Ministry of Health for Gastroenterology.

    Abstract

    Functional constipation is a very common disease among the healthy population and is a cause of serious social discomfort in young and working-age patients. In older people and in defeated patients, it can be cause and contributory cause of aggravation of existing pathologies. For these reasons, this pathology is an important source of expenditure for the national health service and also for the nation and the economy, given the absences of work.
    The problem, often limited to situations that can be handled in outpatient care, sometimes takes on important dimensions, requiring hospitalization and, in particularly severe cases, the need for surgical intervention.
    In my presentation, I try to highlight the importance of targeted diagnostics before proceeding with a therapeutic intervention.
    I focus attention on the differential diagnosis between functional constipation and irritable bowel syndrome with prevalent constipation, because this can change the pathology management. I also point out the importance of dividing the disease into subclasses, because this also radically affects the therapeutic approach.

Day 2

KEYNOTE SPEAKERS
  • The Efficacy of Tocotrienols in the Treatment of Non-alcoholic Steatohepatitis: A Systematic Review

    Jose Reyes Mem. Medical Center
    Philippines
    Biography

    Professor Higinio T. Mappala is a Full-time Medical Specialist III and Administrator at the Jose Reyes Memorial Medical Center, Manila, Philippines, A Board-certified Internist, Gastroenterologist, Endoscopist, Clinical Nutritionist and Clinical Toxicologist; has served as a University Professor and Dean of 2 Medical Schools; a highly-regarded Researcher, with more than 70 scientific papers, and more than 30 international publications. A former Board Director of the Philippine Societies of Gastroenterology and Digestive Endoscopy; an online Research rater of McMaster, Canada and Online Dynamed Research peer-reviewer; a Young Investigator’s Awardee at the World Congress and Asia-Pacific Congress of Gastroenterology; has attended the 3-level training courses on Leadership and Management by the World Gastroenterology Organization held in Florida, USA, Dubrovnic, Croatia and Porto, Portugal. A nominee as one of the Top 100 Leading Physicians 2018, Cambridge Biographical Institute. He is a focused lecturer on NAFLD in local and international conventions.

    Abstract

    Non-alcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease which may progress to non-alcoholic steatohepatitis (NASH). Currently there are no therapeutic strategies for such disease. Only lifestyle modification through diet and exercise were proven to afford some benefit in patients with NAFLD. No pharmacologic agents have so far been approved for the treatment of NAFLD or NASH. Therefore, most clinical efforts have been directed at treating the components of metabolic syndrome, namely obesity, diabetes, hypertension and dyslipidemias. Other interventions are directed at specific pathways potentially involved in the pathogenesis of NAFLD, such as insulin resistance, oxidative stress, pro-inflammatory cytokines, apoptosis, bacterial overgrowth, and angiotensin pathway.
    This lecture aims to show the potential of Tocotrienols as a promising therapeutic option for NAFLD. This is a Systematic Review of the effects of Tocotrienols on Non-Alcoholic Fatty Liver Disease. (NAFLD). Tocotrienols may yet prove to be an effective treatment for Non-Alcoholic Fatty Liver Disease.

  • Cellular Bioenergetics in Patients with Alcoholic Liver Disease

    University of Alabama at Birmingham
    USA
    Biography

    Dr. Singal’s is associate professor of medicine in division of hepatology and director of porphyria center at the UAB, Birmingham AL. His clinical research interests include alcohol and non-alcohol fatty liver disease, porphyria, and renal dysfunction in liver cirrhosis. He has over 110 publications, on editorial board of reputed journals, and research award committees of the AGA and AASLD. Dr. Singal’s research is funded from the Transplant Institute of the UAB, ACG, NIAAA and NIDDK from the NIH, and pharmaceutical industry.

    Abstract

    Alcoholic hepatitis (AH) is associated with 40-50% mortality at 1 month. Liver biopsy is often needed especially for uncertain clinical diagnosis. Corticosteroids (CS) provide 50% survival benefit with their response evaluable only at 1 week. Defects in bioenergetics or mitochondrial oxygen consumption rate (OCR) in peripheral cells are shown in systemic diseases. We tested the hypothesis that AH patients with severe bioenergetics defects will progress to liver failure and be non-responsive to CS (NRS).
    After informed consent, 20 mL blood was collected from ALD patients (with or without AH) and healthy controls. Second 20 mL sample was collected at 1 wk. from AH patients receiving CS. Monocytes and neutrophils were isolated within 30 and cellular bioenergetics and OCR (pmol/min./mcg protein) were obtained using XF96 analyzer (Seahorse Biosciences). Of 78 ALD patients (37 AH) and 40 healthy controls, OCR differed among 63 ALD patients for basal, proton leak, non-mitochondrial, and oxidative burst in monocytes and neutrophils. After controlling for age, WBC, and MELD score, basal and ATP linked OCR predicted diagnosis of AH. Bioenergetics in monocytes improved among responders but not in NRS on follow up assessment at 1 week of therapy. Baseline cellular bioenergetics seems a promising biomarker for personalized medicine in ALD patients for a) diagnosis of AH and b) predicting response to CS and outcome on follow up. Data in larger multicenter population are needed before accepting use of this novel biomarker in clinical practice.

  • Chronic hepatitis C, fibrogenesis and heparan sulfate proteoglycans of the hepatic extracellular matrix

    Cancer Research Center of Lyon (CRCL)
    France
    Biography

    Eve-Isabelle Pecheur has completed her PhD in 1997 from University Paris XI and postdoctoral studies from Groningen University of Medical Sciences (Netherlands). She leads a research group at the Cancer Research Center of Lyon (http://www.crcl.fr/248-Pathogenesis-of-Hepatitis-B-and-C-infections.crcl.aspx?language=en-GB). 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

    Chronic infection by the hepatitis C virus (HCV) is a major cause of liver diseases, predisposing to liver fibrosis and end-stage liver complications, the most serious being hepatocellular carcinoma. Fibrotic tissue remodeling can exert a pronounced effect on cancer initiation and growth. Liver fibrosis is characterized by an overly abundant accumulation of components of the hepatic extracellular matrix (ECM), such as collagen and elastin fibers, with consequences on the biomechanical and biochemical properties of this microenvironment. However, the molecular mechanisms linking infection to fibrogenesis still remain unclear. Here I will focus on the pericellular matrix or glycocalyx, the transition zone between the cell membrane and the ECM. In this zone, I will more specifically focus on heparan sulfate proteoglycans (HSPG), key molecules which bind cytokines and growth factors and modulate their bioavailability in the ECM. Our data suggest that HCV induces major alterations of HSPG metabolism, and a reshuffle of the pericellular matrix to provide a microenvironment favorable for viral replication and persistence. These key events of HCV pathogenesis could contribute to fibrogenesis.

  • Integrating Advance Care Planning Education Early in Cirrhosis Care: An Inter-Disciplinary Model to Increase Uptake

    Grey Nuns Community Hospital
    Canada
    Biography

    Dr. Brisebois is an active member of the Internal Medicine community, and has been an Attending physician on the Grey Nuns Hospital inpatient medicine units since 2000. She graduated from Medical School from the University of Calgary in 1995. After attending a first year of residency at the Mayo Clinic, in Rochester Minnesota. She returned to Canada to complete her Internal Medicine residency, as well as completing a year of Oncology training at the University of Alberta. After experiencing multiple years of helping patients live with chronic illness, she returned to do a year of added competency in Palliative Care which was completed in 2012 in Edmonton. She spent 2012-2013 working both on the Palliative Care Consult Service at the Royal Alexandria Hospital and the Palliative Care Unit at the Grey Nuns Hospital. Currently, she is focused on helping non-cancer patient populations, live well with better symptom control and understanding of how disease progression impacts a patient’s life. She founded PPRISM, a non-cancer palliative care outpatient clinic, which is located in the Kaye Edmonton Clinic at the University of Alberta. She is thrilled to now have adjunct appointments in the Division of Palliative Care and the Division of Internal Medicine, as she is actively involved in caring for patients in both of these domains. Dr. Brisebois is deeply involved in Provincial Networks and co-chairs the Strategic Care Network Committee for Palliative Care Pathway and Guidelines. She is passionate about furthering Provincial education opportunities for families and practitioners, and continues to promote a wider understanding of palliative services in Alberta.

    Abstract

    Advance Care planning (ACP) and goals of care designation (GCD) are being increasingly discussed amongst specialists and generalists involved in the care of patients with cirrhosis. Uptake and adoption of integrating these discussions into standard inpatient and outpatient care have been limited with physicians citing many perceived barriers and limitations. Based upon the literature evidence-base and our experiences, we provide an actionable framework that can be readily implemented into a busy clinic setting, or in in-patient populations, suitable for use by any practitioner. A set of two educational pamphlets, including an ACP cogwheel and figures explaining the course of chronic illness have been implemented. Discussions have involved both a Palliative Care (and Internal Medicine) specialist and a Gastroenterology specialist or General Medicine specialist, as well as an inter-disciplinary team, the patient and their surrogates. The percentage of patients with ACP and GCD documentation has increased dramatically during this time. The use of a formalized process, visual aids, educational pamphlets, has been integrated into care in both the outpatient and inpatient settings. These tools can be customizable based on the underlying gastroenterological (GI) disease, and are hoped to be conversation starters in many clinical settings. In our practice, this assemblage of “best practice tools” has increased the number of outpatients with cirrhosis, and other GI chronic illnesses, who have actively contributed to their GCD prior to acute health events and are supported by well-informed surrogates. We have shown significant value of inter-disciplinary outpatient clinics to educate health practitioners and patients, and wish to promote this globally.

Liver Tumors
Viral Hepatitis C
Hepatitis B and Other Viral Hepatitis
Speaker
  • Clinical Evaluation of Hepatoprotective effect of Bhumyamalki (Phyllanthus amarus) and Phaltrikadi decoction (an Ayurvedic herbal composition) in patients of acute viral hepatitis
    Speaker
    Harbans Singh
    Central Ayurveda Research Institute for Respiratory Disorders
    India
    Biography

    Dr. Harbans Singh has completed his M.D (Kayachikitsa) at the age of 30 years from Himachal Pradesh University, Shimla (India) and completed his PhD (Kayachikitsa) from Rajasthan Ayurveda University, Jodhpur (India) in 2008. He had worked as Associate Professor, Department of Medicine at Desh Bhagat University, Mandi Gobindgarh, Punjab (India). He is presently working as Research Officer (Ay.), Scientist-2 in Central Council of Research in Ayurvedic Science, New Delhi, Ministry of AYUSH, Government of India. He has more than 20 publications of National and International repute. He is engaged in various clinical research projects in the field of respiratory medicine and hepatology. He is also a member several national and international medical and research organizations.

    Abstract

    Background: Hepatitis infection has become a major worldwide health problem because the potential nature of course of the disease to cirrhosis and the hepatocellular carcinoma (HCC). Acute viral infection is the most common cause of all forms of hepatitis. The viral hepatitis have been thought to be self limiting in nature but sometimes majority of patients of viral hepatitis have been observed ending up with a serious complications like hepatic failure, etc. So, the clinical study was planned to evaluate the hepatoprotective effect of Bhyumyamalki (Phyllanthus amarus) and Phaltrikadi decoction (an Ayurvedic herbal composition) on scientific parameters.
    Aim and objectives: To clinically evaluate the hepatoprotective effect of Bhyumyamalki (Phyllanthus amarus) and Phaltrikadi decoction in patients of acute viral hepatitis. Materials and Methods: This prospective, clinical trial was conducted at Department of Medicine, Desh Bhagat Ayurvedic College & Hospital, Mandi Gobindgarh, Punjab. Only those patients were selected for clinical trial, who presented themselves with anorexia, nausea, vomiting, low grade fever, weakness, dark urine, jaundice and tender hepatomegaly with abnormal liver function test (LFTs). Each patient was subjected to series of laboratory tests such asserum bilirubin, AST, ALT, serum alkaline phosphatase, HbSAg, HCV and liver ultrasound before treatment, after 15 days of treatment and after one month of treatment to know the extent of liver damage as well as the rate of response to trial drugs. In the clinical trial, three groups of patients of viral hepatitis have been studied to evaluate the hepatoprotective effect of Bhumyamalki and Phaltrikadi decoction. The first group was given 50 ml of freshly prepared Bhumyamalki decoction, made from 10 gm of crude drug, twice daily. The second group was given a standardized decoction of herbal composition Phaltrikadi decoction, in a dosage of 50 ml made from 10 gm of crude drug, twice daily. The third group was given 100 gm of glucose powder daily.
    Observations and Results: The trial was conducted for one month and liver functions test were periodically evaluated to assess the hepatoprotective effect of drugs under trial. At the end of the trial, group first and second exhibited hepatoprotective efficiency over the control.
    Conclusion: Thus it can be concluded that Bhumyamalki and Phaltrikadi decoction drugs are effective in the management of acute viral hepatitis.

Pediatric Hepatology
Speaker
  • New perspectives in cystic fibrosis associated liver disease in children
    Speaker
    Wikrom Karnsakul
    Johns Hopkins University School of Medicine
    USA
    Biography

    Dr. Wikrom Karnsakul is an assistant professor of pediatrics at the Johns Hopkins University School of Medicine. His clinical interests are in the care of pediatric liver diseases, and general gastrointestinal diseases. Dr. Karnsakul received his medical degree in 1992 from Mahidol University School of Medicine in Bangkok, Thailand. He completed his residency in pediatrics at Advocate Hope Children’s Hospital, University of Illinois at Chicago in 1998 and did a fellowship in pediatric gastroenterology, hepatology and nutrition at Texas Children’s Hospital, Baylor College of Medicine in Houston, Texas. He completed his postdoctoral research training at USDA/ARS Children’s Nutrition Research Center, Baylor College of Medicine. He joined the faculty at Johns Hopkins University School of Medicine in 2008. His research interests center on the understanding and treatment of chronic liver disease, ascites, cholestasis, viral hepatitis, metabolic liver diseases and living related liver transplantation. He has a particular focus on hepatitis E infection. Dr. Karnsakul is also involved in NIH-funded multicenter research studies including the Cholestatic Liver Disease Consortium and Cystic Fibrosis Related Liver Disease Project.

    Abstract

    Cystic fibrosis (CF) is a multisystem genetic disorder caused by a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, encoding the transporter protein responsible for chloride flux across the apical membrane of the epithelial cell. Significant liver disease is an unusual presentation in CF population with the incidence of 4-7%; however an emerging cause of mortality as a result of advanced care in pulmonary, nutritional and lung transplantation care. The cause of CFLD is unknown. The presentation of CFLD varies widely in the CF population with most liver disease occurring at or before puberty. Although dual-pass liver biopsy increases diagnostic yield with the presence of fibrosis, the distribution of fibrotic liver lesions in CFLD is focal and yet the procedure is rather invasive. Currently there are no known risk factors predicting the development of CFLD. The development of non-invasive fibrosis markers has progressed rapidly. Such markers include hyaluronic acid, metalloproteinases, tissue Inhibitors of matrix metalloproteinases (TIMPS), transforming growth factor (TGF-?1), etc. These are not routine laboratory investigations and tend to be expensive. In addition, they may be elevated secondary to fibrosis in extrahepatic organs such as the lungs. Many simple and inexpensive methods such as APR, FIB-4, liver ultrasound have been used as a non-invasive biochemical marker. Furthermore, in CF the role of these tests to reflect CFLD is unclear but may help for early detection of a child with CFLD. Novel therapies exist in CF children. It is still unknown if any therapy can prevent the development and progression of liver disease in CF children.

Molecular and cellular biology
Speaker
Liver growth and repair
HCV/HIV Coinfection
Other Liver Diseases
Speaker
  • Nonalcoholic fatty liver disease
    Speaker
    Amreen Dinani
    Icahn School of Medicine at Mount Sinai
    USA
    Biography

    Amreen Dinani, MD, is an Assistant Professor in the Department of Medicine, Division of Liver Diseases. Dr. Dinani completed her undergraduate degree in Human Biology at University of Toronto in Toronto, Canada and received her Masters in Science and Doctorate of Medicine from the American University of the Caribbean, St. Maarten. She completed her Internal Medicine residency at New York Hospital Queens/ New York Presbyterian Queens in Flushing, New York. She received her Gastroenterology training from McMaster University, Hamilton, Ontario, Canada and Hepatology training at University of Toronto, Toronto, Canada. Dr. Dinani is a member of many professional societies including American College of Gastroenterology and American Association of the Study of Liver Diseases. She introduced non-invasive markers of liver fibrosis and vibration controlled transient elastogrpahy (VCTE) during her 4 year tenure at Dartmouth Hitchcock Medical Centre, Lebanon, New Hampshire. She has served as an Associated Program Director to Gastroenterology Fellowship Program at New York Methodist Hospital, Brooklyn, New York. Dr. Dinani’s clinical and research interests are in nonalcoholic fatty liver disease (NAFLD). She is an investigator for many ongoing clinical trials in NALFD.

    Abstract

    Nonalcoholic fatty liver disease

  • Acute-on-chronic liver failure (ACLF)
    Speaker
    Salem Yousef
    Zagazig University
    Egypt
    Biography

    Dr. Salem Y Mohamed is an assistant professor of internal medicine, in the Gastroenterology and Hepatology unit at the University of Zagazig, Egypt. He received his M.B., B.C H and his M.D. from Zagazig University. He is a consultant physician at the teaching hospital of the same university. In addition to teaching, Dr. Salem is a regular reviewer for many scientific, medical journals, e.g., Journal of Gastroenterology and Hepatology from bed to bench, Journal of Gastroenterology and Hepatology research, The 2016 and 2017 Judging Process for The Undergraduate Awards: Undergraduate Awards. Patron: President Michael D. Higgins Dublin, Ireland, A reviewer at NIH, Southampton, England, World Journal of Surgical Oncology and Journal of Gastrointestinal Cancer

    Abstract

    Acute on chronic liver failure (ACLF) is a distinct clinical syndrome characterized by liver failure due to an acute hepatic injury on an underlying chronic liver disease with high 28-day mortality. Acute insults include alcohol, hepatotropic viruses, and drugs whereas the underlying chronic liver disease is cirrhosis due to alcohol, hepatitis B or C, or NASH. After an acute insult, persistent inflammation, systemic inflammatory response syndrome and the cytokine storm have a central role in the pathogenesis of liver failure and subsequent organ failure.
    Abstinence, antiviral therapy, and withdrawal of harmful drug are specific therapies that could help ameliorate or reverse the liver failure. Liver transplantation is the definitive treatment, and a good outcome is achieved with early transplantation in carefully selected patients; liver dialysis and plasmapheresis can help as ‘bridge therapies.' What about the magnitude of the problem in the Middle East and Africa? Is there any difference between the definitions of ACLF, risk factors, and presentations in different parts of the world?

  • Role of oxidative stress and homocysteine in non-alcoholic fatty liver disease
    Speaker
    Nikhil D Patel
    Jivandeep Hospital
    India
    Biography

    Dr. Nikhil D. Patel (MD, DNB [gastroenterology]) is practising as a consultant gastroenterologist since 12 years. He has around 50 publications in various journals. He has presented more than 80 scientific papers in reputed conferences.

    Abstract

    Non alcoholic fatty liver disease (NAFLD), hepatic manifestation of metabolic syndrome is now the commonest chronic liver disease due to rising obesity and diabetes. NAFLD progresses from simple steatosis (NAFL) to steatohepatitis (NASH) and cirrhosis.
    In presence of suitable genetic and environmental factors (diet/physical activity/gut dysbiosis), insulin resistance (IR) and obesity results in adipose dysfunction, which triggers proinflammatory response, decreased lipolysis, increased de-novo lipogenesis and further increased IR. These events increase free fatty acid (FFA) flux to liver, which leads to triglyceride accumulation (NAFL). Toxic levels of FFA in liver trigger increased ?-oxidation and mitochondrial dysfunction (MD). Obesity, homocysteine and environmental factors trigger endoplasmic reticulum stress (ERS). MD and ERS result in reactive oxygen species (ROS) production. ROS activates antioxidant mechanisms (consisting of enzymes like Superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase; and non-enzymes like vitamin A, C, E, ?-carotene and glutathione) which scavenges them, but over production of ROS results in depletion of antioxidants. Homocysteine adds to ROS production and suppresses antioxidants. Oxidative stress results in proinflammtory cytokine production, lipid peroxidation (measured by Malonildialdehyde) and protein adducts production leading to cell injury, inflammation and cell death leading to NASH. In addition, it triggers hepatic stellate cell activation leading to fibrosis and subsequently cirrhosis. Oxidative stress also produces DNA damage leading to future hepatocellular carcinoma. So, oxidative stress remains central to development of NASH and cirrhosis.
    In clinical practice, differentiating NAFL and NASH requires liver biopsy because non-invasive scoring systems are not sensitive. Measuring homocysteine and enzymes (like glutathione transferase, glutathione peroxidase, catalase, etc.) may prove helpful to define progress to NASH. Also targeting these molecules by newer therapeutic strategies may halt progression of NAFLD.

Liver Transplantation and Liver Surgery ( experimental & clinical)
Liver Inflammation and Immunology
Speaker
Poster Presentations & YRF (Young Research Forum)
Speaker
  • Non-alcoholic fatty liver disease and its development to hepatocellular carcinoma in patients with obesity and metabolic syndrome
    Speaker
    Daniel Toman
    Ostrava University
    Czech Republic
    Abstract

    Backgorund The rates of obesity and the metabolic syndrome are increasing worldwide, therefore clinical studies have been undertaken to examine for links with Nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) NAFLD represents the hepatic manifestation of the metabolic syndrome. It is associated with the presence of insulin resistance and type 2 diabetes mellitus. HCC has been registered as a most most frequent type of cancer in type 2 diabetes . Methods Age, obesity, insulin resistance, and overall development of metabolic syndrome are the major risk factors associated with development of NAFLD. From longitudinal studies performed in the Western countries, it has been shown that rates of HCC from NASH are similar to those of HCC from infection with the hepatitis C virus. Liver biopsy is an invasive procedure and is not a suitable option as a routine screening tool for this common disease and a new diagnostic procedures and scoring systems that could non-invasively distinguish simple steatosis from NASH are emerging. Results Visceral body fat is related to the degree of inflammation and fibrosis in NASH. The pro-inflammatory environment can impact the liver and other tissues and patients with more visceral fat had higher rates of HCC recurrence. Part of patients who are initially diagnosed as clinically non-cirrhotic NAFLD could be at high risk of HCC development, and employing only standard follow-up procedures for cirrhotic patients would not be enough. Although current guidelines recommend regular HCC surveillance for cirrhotic patients, HCC can develop in the absence of cirrhosis in NAFLD. Discussion With the increasing prevalence of NAFLD it is becoming clear that it will contribute to increasing incidence of HCC as well. Identifying a high-risk subpopulation in HCC development among non-cirrhotic NAFLD patients is imperative. Obesity almost doubles the risk of HCC. The diagnosis of HCC might be considered in obese and/or diabetic patients with liver nodules, even if they do not have others manifestations of chronic liver disease. Research reported in this press release presentation was supported by the Ostrava University, The Czech Republic, under grant award number SGS03/LF/2018.

  • 4-Methylumbelliferone reduces liver fibrosis in CCl4-treated mice and prevents hepatocyte necrosis caused by paracetamol.
    Speaker
    Adelya Gabdulkhakova
    Skolkovo Institute for Science and Technology
    Russia
    Biography

    Adelya Gabdulkhakova has graduated from Sechenov Medical University in 2016 and studies Translational Biomedicine at Skolkovo Institute of Science and Technology, Moscow. The focus of her research is on the pathophysiology of hepatocytes damage.

    Abstract

    Background and aims: Liver fibrosis is a potentially morbid condition with the unmet therapeutic needs. Previously, in vivo siRNA silencing of hyaluronan synthase 2 (HAS2) in CCL4-treated mice reduced liver fibrosis but augmented myofibroblast density. This prompted us to investigate the therapeutic potential of 4-methylumbelliferone (4-MU), an inhibitor of hyaluronan production, on liver fibrosis, hyaluronan deposition and expression of profibrotic genes in a chemically induced liver injury.
    Methods: 8-week old female BALB/c mice (n=8 per group) were subjected to liver injury by CCl4 inhalation twice a week for 15 mins, for 2 or 4 weeks. 4-MU (800 mg/kg) was given daily by gavage starting i) two weeks before CCL4 inhalation; ii) simultaneously with CCl4; iii) 2 weeks after the start of CCL4 treatment; iv) for 2 weeks after the discontinuation of CCL4 treatment. In all groups, 4-MU treatment continued until sample collection.
    Paracetamol (450 mg/kg, by gavage) was given daily for 1 month to a separate set of mice, with or without 4-MU (800 mg/kg). The liver lobes were collected at different time points to assess mRNA levels of myofibroblast-specific genes expression by qPCR and for histological analysis. The extent of fibrosis was evaluated using Mallory staining. Hyaluronan, collagen and alpha smooth muscle actin (?SMA) were revealed immunohistochemically. The images were taken with a Keyence BZ9000 microscope and processed with ImageJ software.
    Results: The area of fibrosis in the CCl4 experimental group pretreated with 4-MU was reduced by 55%, as assessed by Mallory staining. Smaller but still significant effects of 4-MU were registered when applied after the liver injury was established. The expression levels of myofibroblast-specific genes Fstl1, ?SMA and Col1 were maximally upregulated (up to 3 fold) after 2 weeks of CCL4 inhalation and reduced in all experimental groups administered with 4-MU. Discontinuation of CCl4 inhalation also demonstrated decreased levels of gene expression, but the effect was enhanced in the group treated with 4-MU. Immunofluorescent staining revealed reduced ?SMA expression, and colocalized collagen and hyaluronan deposition in 4-MU-treated mice. Paracetamol caused extensive necrosis but did not induce significant fibrosis, and necrosis was dramatically reduced in mice treated with 4-MU. Adding 4-MU to TGFb2-stimulated 3T3 fibroblasts in vitro reduced both HAS2 and hyaluronidase 2, and increased hyaluronidase 1 expression.
    Conclusion: 4-MU protects hepatocytes from CCL4- and paracetamol–induced injury. 4-MU treatment reverses the established fibrosis and accelerates the liver regeneration via a reduced activity of myofibroblast-specific genes. These results suggest 4-MU to be a promising candidate for both preventing and treating liver fibrosis and to be further tested in clinical trials.

  • Characterization of laboratory and clinical findings of patients diagnosed with drug-induced liver injury (DILI) as a tool to aid in diagnosis
    Speaker
    Itay Ashkenazi
    Tel Aviv University
    Israel
    Abstract

    Background & Aim: Drug Induced Liver Injury (DILI) is a diagnosis the importance of which has become increasingly clear in recent years as a result of the combination of an increase in the number of reported cases each year and the potential for damage; DILI is the most common cause of Acute Liver Failure in the United States and a major cause of drug termination at various stages of development and marketing.
    Despite its importance, DILI is often underdiagnosed or suffers from a diagnostic delay, mainly due to a lack of a pathognomonic test, resulting in a PER EXCLUSIONEM diagnosis. Various attempts to find a more efficient diagnostic process met with partial success and the diagnostic challenge persists. The main objective of the study is to try to find unique characteristics for patients who have been diagnosed with DILI in order to try to create a basis for dealing with this diagnostic challenge.
    Methods: A retrospective observational study of 50 patients hospitalized at "Shaare Zedek" Medical Center diagnosed with DILI.
    Results & Discussion: In accordance with the literature on DILI, we found that the most common injury was hepatocellular (52% of the patients), that most of the cases were women (56% of the patients), that the prevalence increases with age (70% of the cases were over the age of 51) and that there is a relationship between the age and the sex of the patient to the type of injury. In accordance with studies conducted in the United States, the most common drugs described in our study as the cause of DILI are antibiotics (34% of the cases).
    The hepatocellular enzymes levels in patients with hepatocellular injury ranged from several hundreds to a thousand, and in the majority of the cases were higher than 10 times the upper limit of the norm (AST in 80.8% of the cases and ALT in 53.8% of the cases). These ranges correspond to the ranges described in the literature for toxic liver injury.
    In our study, we have not been able to verify the worldwide trend of increasing prevalence of DILI.
    In general, the severity of the cases in our study was relatively mild, as expressed in the absence of mortality, in the absence of liver failure and in relatively low bilirubin levels. Previous studies have found that the most unfavorable outcome was of patients with hepatocellular injury. In contrast to that, in our study, the worst prognosis was of patients presented with mixed injury.
    In contrast to viral hepatitis, we found that the De Ritis (AST / ALT) ratio in DILI is generally greater than 1 (in 82% of cases).
    Conclusions: 1. Despite the increasing prevalence of DILI according to literature, we have not been able to confirm this trend. In our opinion this is partially due a logistic difficulty - the absence of a specific diagnosis code for DILI, i.e., patients whose main diagnosis is DILI are coded under another major diagnosis and the DILI is "hidden" under a general hepatic diagnoses such as "Elevated Liver Enzymes" or even under a non-hepatic diagnosis as a free text. We respectfully submit that the ICD coding system should include DILI as a major diagnosis.
    2. We suggest considering using the De Ritis ratio as a diagnostic aid. Our study did not include a control group of viral hepatitis patients, so we can rely only on information from the literature, but this information is consistent across a large number of studies – Viral hepatitis is characterized by a De Ritis ratio <1, In contrast to that, most of the patients in our study are characterized by a De Ritis ratio>1.

  • Laparoscopic liver resections: an innovative approach to the liver in a single centre experience
    Speaker
    Francesco Lattanzio
    Chirurgia Generale Balestrazzi , Policlynic Hospital
    Italy
    Biography

    Dr. Francesco Lattanzio received his medical degree from the University of Bari (Italy). He completed his general surgery residency at the University of Trieste (Italy). During his training he was at C.H.U. Toulouse (France) with Pr. Gilles Fourtanier, secretary of the Societé Francaise de Chirurgie Endoscopique, at C.H.U. Jean Verdier (Assistance Publique Hopitaux de Paris) with Pr. Gerard Champault, President of the Societé Francaise de Chirurgie Laparoscopique, at C.H.U. Avicenne (Assistance Publique Hopitaux de Paris) with Pr. Jacques Azorin, past President of Societé Francaise de Chirurgie Thoracique et Cardiovasculaire and with Pr. Luis Perez-Ruiz at Lleida University in Catalunya (Spain). He is certified in “Chirurgie Hèpatobiliaire” at University Paris Sud with Pr. Denis Castaing. Dr. Lattanzio is associated with the development of many advanced laparoscopic operations including colorectal cancer, small bowel obstruction, and incisional hernia repair. He currently works at Dimiccoli Hospital in Barletta (Italy).

    Abstract

    Laparoscopic liver resections (LLR) represent the new frontier of liver surgery. During the last decade indications for the laparoscopic approach to the liver have been widely extended, from peripheral benign lesions to malignant neoplasms, difficult localizations and major resections.
    Laparoscopic liver surgery was slower to develop than other fields of laparoscopic surgery because of a steep learning curve, and fear of uncontrolled bleeding or gas embolism. However, LLR is associated with significant advantages of laparoscopic procedures. The aim of this retrospective study is to evaluate the extent and safety of the learning curve for LLR.
    We retrospectively analyzed 87 patients who underwent a LLR from July 2010 to November 2017 performed by a single senior surgeon. At the start of experience the indication was a single lesion, whereas in the last years an increasing number of patients was enrolled for laparoscopic intervention, according to the learning curve.
    Diseases included liver cancer, hepatic hemangioma, focal nodular hyperplasia, liver abscess, and metastatic liver cancer. The diagnosis was a malignant neoplasm for 53 patients (61%), a benign lesion for the remaining cases.
    In 45 patients a synchronous procedure was performed (4 right colectomy, 6 left colectomy, 8 rectal resection, 2 gastric resection, 21 cholecistectomy, 4 for other procedures) .
    35 patients were males and 42 were females, with a mean age of 60 years (range 23-88). 81 patients (93%) had a good preoperatory hepatic function, assessed with A Child-Pugh score.
    We performed 63 wedge resections (72%), 2 segmentectomies, 4 right lateral bisegmentectomies, 13 left lobectomies (15%), 4 left hepatectomies and 1 robotic right hepatectomy, the latter converted for intraoperatory bleeding. Median operative time was 120 minutes (35-330). There were no intraoperative or postoperative deaths and 26% of morbidity (ascites in 7 patients, fever in 7 patients, pneumonia in 4 patients, 1 needed blood transfusion and 3 surgery-related complications occurred). Only one major complication (grade III of Clavien-Dindo classification) was observed, in a patient who received a synchronous proctectomy and needed reoperation for anastomotic dehiscence. The median time of discharge was 5 days (range 2-11). A negative histological margin (R0) was obtained in 88% of malignancy cases.
    In our experience laparoscopic surgery is a safe option for hepatic resection in benign such as malignant lesions, good patient selection and refined surgical technique are the keys to successful of LLR, especially at the beginning of the learning curve as well as the experience of the surgeon in advanced laparoscopic procedures and hepatobiliary surgery.

  • Green tea confers protection against cigarette smoke-induced biochemical perturbations in Tuberculosis Patients
    Speaker
    Lokesh Thippannagari
    Sri Krishnadevaraya University
    India
    Biography

    Abstract

    Cigarette smoking is common among persons with alcohol dependence. Smoking and alcohol consumption cause damage to body organs. Many studies have suggested that these two factors are also responsible for increasing effect of Mycobacterium tuberculosis in lungs and other organs of humans. Tuberculosis is a global health disease. The present study investigates the effect of green tea consumption on confirmed cigarette smokers of TB. Blood samples from Eighty-four human volunteers categorized into seven groups viz., control, TB smokers, TB smokers with Green tea were selected for this preliminary study to investigate changes in membranes of erythrocytes by consuming green tea. Data obtained from the study suggested a significant increase in the percentage of Haemolysis in experimental groups when compared with control group and were in the order TB smokers > TB smokers with green tea > controls indicating an additive effect of green tea on cigarette smokers of TB. Liver function tests (LFTs) are commonly used in clinical practice to screen for the liver disease. The liver markers AST, ALT, GGT in TB smokers were increased and TB smokers with Green tea were significantly decreased. The present study divulges that green tea contains catechins can reduce the abnormalities of cigarette smoking effect by ameliorating the oxidative stress. This finding reveals that the possibility of green tea may provide protection from cigarette-caused changes in TB patients.

  • Dysregulation of GCLC by NRF2 signalling disrupts anti-oxidant pathway central to most cancers and RAC1 protein modifications in cancer
    Speaker
    Dharaneeswar Reddy Mantri
    University of Mysore
    India
    Biography

    Dharaneeswar Reddy Mantri (MSc, Genetics) 2017, University of Mysore, India. Dharaneeswar Is a native of Andhra Pradesh, India. His master’s research focused on the role of NRF2 in ROS and RNS dependent cancer formation and Early detection of cancer. His interest lies in the continuation of his research on the biomarker for early detection of cancer. He did his bachelors in biochemistry at Sri Krishnadevaraya University, India.

    Abstract


    Background: NRF2 is ubiquitously expressed transcription factor regulating cytoprotective genes such as SOD, catalase, TRX and GPX. NRF2 is additionally kenned to be a crucial regulator of cell survival and oncogenic pathways and is found to be up-regulated across most cancers. Ergo, investigating the gene expression status and exome sequencing of upstream and downstream neighbours of NRF2 is imperative to understand the oncogenic manifestation central to NRF2. RAC1 and GCLC are such upstream and downstream molecules whose regulation status is unknown across many cancers.

    Methods: We estimated the GCLC and RAC1 transcripts from the RNA isolates from 15 cancer samples of different kinds. cDNA was constructed and authentic-time quantitative PCR was performed utilizing SYBR green assay and the fold change was calculated to understand the regulation status.

    Results: The upstream gene RAC1 and downstream genes GCLC were found up-regulated across samples with a fold change >5 fold. We identified >50 nonsynonymous deleterious mutations in the 11,416 whole exome cancer cohort samples. Performing evolutionary profile betokened no conservancy for the observed mutations.

    Discussion: Integrating the mutations and expression status of GCLC, RAC1 and NQO1, revealed the up-regulation of NQO1 due to the activation of the PI3 kinase, and HMOX1, while inactivating of BET and KEAP1 concurrently. Up-regulation of GCLC designates NF-KB and HMOX1 to be activated, while CYB5R4 and BET are negatively regulated. The dysregulation of these genes disrupts the free radical scavenging pathway, cell death and survival pathways, and anti-apoptotic pathways. These genes are majorly expressed in the detoxifying organs like liver and kidney. This study shows that the NRF2 and its upstream molecules are found to be efficacious biomarkers in the future and early detection of cancer additionally will come true with this efficient biomarkers.

    Keywords: Biomarker, Free radicals, Detoxifying, NRF2, Anti-apoptotic

E- Poster
Speaker
  • A public health analysis on gaps in disease monitoring and opportunities for improved care for management of hepatitis B & C
    Speaker
    Faisal Akhtar
    Ochsner Health System
    USA
    Biography

    Abstract

    Hepatitis B and Hepatitis C have been a major disease causing agents among humans since they were discovered in 1960s. Both causes jaundice like symptoms initially but then their prognosis and treatment are somehow different and depending upon many demographic details like age and susceptibility of the patients and any other co morbid conditions, they clinically present primarily with hepatitis, and can have many adverse effects or even can be life threatening at times if not treated properly. But there epidemiological background and their findings in terms of morbidity, mortality and case fatality rates are different. From the disease burden and impact on the healthcare system, and the prevention of the two diseases, both are quite different. Treatment and management options along with prevention and control, each of these two share its unique strategies of handling the disease. The purpose of this review is to highlight the gaps in disease monitoring and to find ways and opportunities which can lead to improved care and better management of Hep B & C, locally and globally. Online databases were searched and peer-reviewed articles were selected. Key issues identified were lack of education globally in resource limited settings, leading to decrease understandings of the potential hazards associated with needle sharing, lack of access to healthcare, because of lack of insurance. Failure of compliance to vaccination leading to increase MTCT related infections. Increase global travelling demands a systematic programs in most immigrant receiving countries to screen for HBV/HCV infections. Delayed FDA licensing for new drugs hampers the treatment of CHB among children. With advancement in science, an era has come where an effective vaccine against HCV will definitely help in eradicating the infection.

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