Day 2 :
Keynote Forum
Dr. Maxwell M Chait
Columbia University College of Physicians and Surgeons, USA
Keynote: Lower GI bleeding in patients with cirrhosis
Time : 09:00-09:30
Biography:
Maxwell M Chait completed his MD degree 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 and Assistant Professor of Medicine 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. LGIB occurs in approximately 20% of all patients with cirrhosis who present with gastrointestinal bleeding (GIB). 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.
- Workshop
Location: Prestwick
Session Introduction
Dr. Sen-Yung Hsieh
Chang Gung Memorial Hospital, Taiwan
Title: The cirrhosis micro-environment and hepato-carcinogenesis
Time : 09:40-10:40
Biography:
Sen Yung Hsieh has completed his MD from National Yang Ming University, Taipei, Taiwan and PhD from University of Pennsylvania, PA, USA. He completed his clinical training in Gastroenterology and Hepatology at Chang Gung Memorial Hospital. Currently, he is the Director of the Department of Medical Research and Development, Director of the Clinical Proteomics Center, and Professor of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan. He has published many papers in reputed journals including Hepatology, J Hepatology, Mol Cell Proteomics, and Proc Natl Acad Sci, USA and has been serving as an Editorial Board Member of many reputed journals.
Abstract:
Hepatocellular carcinomas (HCC) are unique among all human cancers for its unusual cultivating cirrhosis microenvironment. More than 80% of HCC develop in cirrhotic livers with a propensity to multifoci, unusually high tumor vascularity, high recurrence, high local invasion and relatively systemic tumor dissemination and relatively resistance to cytotoxic chemo and molecular target therapies. These unique features contribute to very dismal outcomes of patients with HCC. Cirrhosis is not only a disease of the liver but also exerts greatly changes in the general physiology of the body which might play significant roles in the development and progression of liver tumors. However, little has been known why HCC prefers developing in cirrhotic liver, how cirrhotic liver fosters HCC development and progression, and how the tumor progression and dissemination are orchestrated by the unique systemic cirrhosis micro environment. This workshop will focus on updating our knowledge on the roles of the cirrhosis local and systemic microenvironment in hepatocarcinogenesis, tumor progression and clinical outcomes.
- Hepatitis: Care and Cure
Diagnosis and Liver Pathology
Assessment of Liver Diseases
Location: Main Hall 1
Chair
Dr. Trent W Nichols
AMRI, USA
Co-Chair
Dr. Hosny Salama
Cairo University, Egypt
Session Introduction
Dr. Parveen Malhotra
PGIMS, India
Title: Epidemiological profile of patients at a newer hub of hepatitis C in India
Time : 12:25-12:50
Biography:
Parveen Malhotra got a Silver Medal in Final Prof. MBBS and his MD Thesis on Role of Topiramate in refractory seizures was recommended. He did DNB Gastroenterology under renowned Hepatologist Dr. Dharmesh Kapoor from Global Hospital, Hyderabad. He became Head and established department of Gastroenterology at PGIMS, Rohtak in August, 2010. He has fifty publications and regularly presenting posters & papers at various national and international conferences. He is Post Graduate Teacher and Member of both Postgraduate and Undergraduate Board of studies as well as Academic council at University of Health Sciences, PGIMS, Rohtak. He got first prize i.e. N.L.Patney Award in paper presentation on Hepatitis C Epidemic in Haryana at IAMCON-2013 at Kota. He is Principal Nodal officer of dedicated Hepatitis C center, first of its kind in India where free treatment is being given to patients suffering from above disease.
Abstract:
Introduction: The epidemiology of hepatitis C in India has not been studied systematically. Most of the studies of the prevalence of hepatitis C have been based in blood banks with the assumption that blood donors are surrogates for the population at large. However, this assumption may be incorrect. Aims & Objectives: To study epidemiological profile, geographic foci, assess risk factors, genotypes and viral load in patients infected with Hepatitis C Virus. Materials & Methods: It was an epidemiology based prospective study conducted at medical gastroenterology department of our institute. The record of each patient was meticulously maintained and sample consisted of 1000 (one thousand) patients. Only those patients confirmed for hepatitis C infection by PCR analysis were included consecutively. Results: Majority (65%) of the subjects was male. 81% belonged to rural areas and 84% were married. The age distribution showed a sharp peak between the age group 20 to 35 years i.e., 38%. History of previous surgery and tattooing appeared as major risk factors. 31.75% patients had history of a major or a minor surgery and 32% was having tattoos. Around 12% had history of receiving blood transfusion, 23.5% of the patients had a history of jaundice sometime in the past. Only 4.25% of the patients each had a history of I.V drug abuse and the same number (4.25%) had a history of sexual relations with multiple partners. None of the patients in this sample had a history of dialysis. 72.25% of the patients were asymptomatic. Most of them were found to have HCV infection at screening camps followed by screening during preanaesthetic checkups and blood donation. Malaise (10.25%), pyrexia of unknown origin (7.25%), diffuse abdominal pain (5.75%) and joint pain (4.5%) were the major complaints in the symptomatic patients. In this study sample genotype 3 was most common (58.25%). Curiously even genotype 4 (21.75%) and Genotype 1(17.20%) has substantial presence. Only 2 cases of genotype 5(0.2%) and 1 case of genotype 6 (0.1%) were seen. There was no case of genotype 2. Genotype could not be determined in 2.50% patients due to low viral load.
Dr. Vani Malhotra
PGIMS, India
Title: Hepatitis B Infection During Pregnancy –Experience At Tertiary Care Centre Of North India
Time : 15:00-15:25
Biography:
Vani Malhotra is working as Professor in Department of Gynecology & Obstetrics, PGIMS, Rohtak, India. She did her MD in the years from 2000-2003 and her thesis was commended. She is working as Faculty at PGIMS, Rohtak, since 2006. She has till now fifty publications in both international and national journals. She is regularly presenting free papers, posters and chairing sessions at various national and international conferences. She is Member of Undergraduate and Postgraduate board of studies at PGIMS, Rohtak. She is working both as Guide and Co-guide in many research projects. She is also supervising many national projects initiated at Gynecology & Obstetrics Department of PGIMS, Rohtak, India.
Abstract:
Aim: The aim was to investigate the seroprevalance of hepatitis B surface antigen (HbsAg) in pregnant women. Material & Methods: Fifteen thousand pregnant women were evaluated using history, examination and tested for serum HbsAg using commercial enzyme immunoassay kits. For HbsAg positive women, detailed biochemical evaluation including liver function tests, ultra sonogram abdomen and complete hepatitis B profile including HbeAg, HbeAb, IgM Anti HbC and HBV DNA analysis was also done by polymerase chain reaction (PCR). Results: Of 15,000 women studied, 52 tested positive for HbsAg. Of these 52 women, 8 presented with acute hepatitis and 44 had chronic hepatitis. The highest HbsAg positivity rate was seen in age group of 21-25 years. Assessment of risk factors revealed history of tattooing in 22 women. HbeAg and HBV DNA were highly positive in 12 patients. These were given tablet lamivudine to reduce the vertical transmission. Conclusion: Seroprevalance of HbsAg in antenatal women was found to be 0.34%.
Dr. Garima Mittal
SRHU, India
Title: Effect of isolation measures on the profile of hepatitis C virus infection in haemodialysis unit of a tertiary care hospital
Time : 16:50-17:15
Biography:
Garima Mittal (MBBS, MD Microbiology) is currently working as Assistant Professor in the department of Microbiology in HIMS, Dehradun. She is in-charge of serology section which is a NABL accredited laboratory, HIV State reference lab and is part of hospital infection control committee. She has published more than 15 papers in reputed journals, reviewer of few journals and is involved in many projects of national repute.
Abstract:
Introduction: Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality in haemodialysis (HD) patients. Several studies demonstrated nosocomial transmission of HCV among HD patients. Aim: We aimed to compare the prevalence and incidence of HCV seropositivity before isolation and after isolation among a group of Indian haemodialysis patients in a tertiary care hospital setting. Methods: We compared our patients on regular haemodialysis in two different time period of 18 months each. First group included 97 patients on regular haemodialysis not following strict isolation of the HCV sero-positive patients and were followed over a period of 18 months, and the second group included 113 patients on regular haemodialysis following this strict isolation again over a period of 18 months. In these patients HCV status were done at every 3-4 months interval to look for seroconversion. Results: There was a significantly higher incidence of HCV seroconversion among the patients who were on haemodialysis and were not following strict isolation (17.17%) than those following strict isolation (3.03%). History of blood transfusions, duration of HD, dialyser reuse and dialysis at multiple centers were found to be important risk factors for anti-HCV positivity. Conclusions: In Haemodialysis units with a high prevalence of HCV seropositivity, strict isolation of HCV+ patients in combination with implementation of universal work precaution measures can limit the spread of HCV infection in HD patients.
Dr. Jing-Bo Wang
The Fourth Military Medical University, China
Title: A decline of LAMP- 2 predicts ursodeoxycholic acid response in primary biliary cirrhosis
Time : 11:35-12:00
Biography:
Jingbo Wang completed his MD and PhD in the Department of Digestive Disease and Postdoctoral training in the Department of Pathology at Fourth Military Medical University. He is an Assistant Professor of Division of Hepatology, Xijing Hospital of Digestive Diseases. His main research focuses on the diagnosis, treatment and molecular mechanism involving in Primary Biliary Cirrhosis (PBC). He has published more than 13 papers in Journal of Proteomics, Scientific Reports and reviewed manuscripts for many international journals.
Abstract:
Biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) is variable. We have previously reported that augmented expression of lysosome-associated membrane protein 2 (LAMP-2) was correlated with the severity of PBC. This study aimed to determine whether serum LAMP-2 could serve as a predictor of biochemical response to UDCA, which was assessed after 1 year of UDCA treatment in PBC patients by a retrospective analysis. We found that baseline of serum LAMP-2 level increased in PBC, especially in patients with stage III-IV (p=0.010) or TBIL >1mg/dL (p=0.014). The basal level of serum LAMP-2 was higher in non-responders than that in responders, but the difference was statistically insignificant. However, after UDCA treatment, the serum LAMP-2 level decreased prominently in the first 3 months, which was more obvious in responders. Further studies showed that the 35% decline of LAMP-2 level after treatment for 3 months could be stated as an indicator of UDCA response with the sensitivity of 62.9% and 63.5%, specificity of 75.0% and 64.1% based on Paris criteria and Barcelona criteria respectively. Together, a decline in LAMP-2 might be a prognostic indicator to predict the response to UDCA in patients with PBC.
Dr. Huang Jiwei
Sichuan University, China
Title: Intermittent hepatic inflow occlusion during partial hepatectomy for hepatocellular carcinoma does not shorten overall survival or increase the likelihood of tumor recurrence
Time : 12:30-12:55
Biography:
Huang Jiwei has completed his MD and PhD at the age of 33 years from West China School of Medicine, Sichuan University, China. He is an Assistance Professor of Department of Liver Surgery, West China Hospital, Sichuan University. He has published more than 15 papers in reputed journals and has been serving as an Editorial Board Member.
Abstract:
Aim: To investigate whether the long-term outcomes of Hepatocellular carcinoma (HCC) was adversely impacted by intermittent hepatic inflow occlusion (HIO) during hepatic resection. Study design: We performed a cohort study of 1549 HCC patients who underwent hepatic resection between March 1998 and March 2008. Intermittent HIO was performed in 931 patients (HIO group); of which 712 patients had a Pringle maneuver as the mechanism for occlusion (PM group), and 219 patients had selective hemi-hepatic occlusion (SO group). There were 618 patients that underwent partial hepatectomy without occlusion (OF group). Results: The 1, 3, and 5 year overall survival (OS) rates were 79%, 59%, and 42% in the HIO group, and 83%, 53% and 35% in the OF group, respectively. The corresponding recurrence free survival (RFS) rates were 68%, 39% and 22% in the HIO group, and 74%, 41% and 18% in the OF group, respectively. There was no significant difference between the two groups in OS or RFS (p=0.325 and p=0.416). Subgroup analysis showed patients with blood loss over 3000 ml and those requiring transfusion suffered significantly shorter OS and RFS. Blood loss over 3000 ml and blood transfusion were independent risk factors to OS and RFS. Conclusions: The application of intermittent HIO (PM and SO) during hepatic resection did not adversely impact either OS or RFS in patients with HCC. Hepatic inflow occlusion is still a valuable tool in hepatic resection, because high intraoperative blood loss resulting in transfusion is associated with a reduction in both OS and RFS.
Dr. Jian Guan
Peking Union Medical College (PUMC) Hospital, China
Title: Cholesterol-conjugated let-7a mimics: Antitumor efficacy and toxicity in preclinical xenograft models of human hepatocellular carcinoma
Time : 14:55-15:20
Biography:
Jian Guan received her MD from Peking Union Medical College (PUMC) in 2001 and completed Postdoctoral research work in Law Institute of Chinese Academy of Social Sciences. She is Associate Professor, department of pathology & Professor, department of scientific research & Lawyer, PUMC Hospital. She is Deputy Secretary-General, Chinese Society of Medical Science Research Administration. Her research interests are mainly in molecular oncology, medical ethics and IP. She has published more than 30 papers in reputed journals and has been serving as an Editorial Board Member of “Advance of Cancer” and “Chinese Medical Research Management”.
Abstract:
Therapy with let-7 miRNAs is a potential strategy for human (HCC). A major challenge for the clinical utility of let-7 miRNAs is the lack of an effective, non-toxic carrier. Recently we confirmed the antitumor efficacy and potential off-target effects of cholesterol-conjugated let-7a mimics (Chol-let-7a) in preclinical models. Subcuneous and orthotopic xenograft were treated with Chol-let-7a or negative control miRNA through local injections or systemic delivery. Ultrasonography was used to evaluate tumor growth and metastasis. Histopathology and ultra structural features of the liver and kidney were used to evaluate toxicity after systemic treatment. Chol-let-7a inhibited HCC growth (Inhibitory rate, 56.3%) and tumor invasion when delivered by means of local injection in a subcutaneous xenograft model. Chol-let-7a was shown to effectively carry let-7a to the target tumors and produce satisfactory antitumor effects (Inhibitory rate, 66.5%) in an orthotopic xenograft model when administered systemically. In addition, Chol-let-7a-treated tumor cells showed no significant atypia and mitoses were very rare per unit of measurement in most areas after systemic therapy. Let-7a-treated xenografts revealed a significant up regulation of let-7a miRNA, and down regulation of three ras genes and ras proteins, especially n-ras/N-RAS was most strongly affected at the transcript and post-transcriptional levels. After continuous Chol-let-7a treatment, only some non-specific reaction changes were observed in liver and kidney in nude mice. These results suggested that Chol-let-7a produces inhibitory effects when administered locally and systemically. Chol-let-7a induced mild damage in liver and kidney after long-term treatment. Thus, systemically delivered Chol-let-7a is a promising therapeutic drug candidate for HCC.
Dr. Chiou-Hwa Yuh
Institute of Molecular and Genomic Medicine, ROC
Title: Distinct roles of α-1,2-mannosidase subtypes in hepatocarcinogenesis: MAN1A1 is an oncogene and MAN1C1 is a tumor suppressor gene
Time : 16:15-16:40
Biography:
Chiou-Hwa Yuh has completed her PhD from National Yang-Ming University in Taiwan, and Postdoctoral studies from California Institute of Technology in USA. She was famous in Developmental Gene Regulatory Networks. She initiated the systematic analysis of hepatocellular carcinoma (HCC) in mouse model, and established transgenic zebrafish model. She further developed the drug screening platform to identified novel small molecules which are effective in treatment HCC and lower toxicity compared to Sorafenib. She has published 41 papers in reputed journals and has been serving as an editorial board member of repute journals.
Abstract:
Deregulation of α-mannosidase can result in cancer, although the mechanism remains unclear. Here, we report the distinct roles of α-mannosidase subtypes in the formation of hepatocellular carcinoma (HCC). Clinicopathological analysis revealed that the clinical stage, tumor size, tumor type, α-fetoprotein level and invasion status were positively correlated with the expression level of MAN1A1, MAN1B1, and MAN1A2. In contrast, the expression of MAN1C1 was decreased as early as stage I HCC. Survival analysis showed that high MAN1A1, MAN1A2 or MAN1B1 and low MAN1C1 expression levels were significantly correlated with poor survival. Functionally, the overexpression of MAN1A1 promoted proliferation, migration and transformation in vitro as well as metastasis in transgenic zebrafish. Conversely, the overexpression of MAN1C1 reduced the cellular migration ability both in vitro and in vivo, decreased the colony formation ability, and shortened the S phase of the cell cycle. Furthermore, the expression of cell cycle/proliferation- and migration-related genes was increased in MAN1A1-overexpressing cells but decreased in MAN1C1-overexpressing cells. Finally, MAN1A1 activated the expression of key regulators of the unfolded protein response (UPR) and the active spliced form of XBP1. Subsequently, treatment with an ER stress inhibitor decreased the expression of cell cycle/proliferation-related genes. Using a zebrafish model of liver-specific overexpression of MAN1A1, we observed steatosis and inflammation at earlier stages and HCC formation at a later stage. These data suggest that the up-regulation of MAN1A1 activates the UPR and initiates metastasis. Thus, our data demonstrate that MAN1A1 represents a novel oncogene in hepatocarcinogenesis, whereas MAN1C1 acts as tumor suppressor gene.
Dr. Amr Amin
UAE University, UAE
Title: Crocin, a saffron-based drug, does wonders against hepatocellular carcinoma: In vitro, in vivo and in silico approaches
Time : 15:20-15:45
Biography:
Amr Amin has completed his PhD at University of Illinois at Chicago, and received a Post-doctoral training in the field of molecular genetics at the University of Pennsylvania School of Medicine. He started his academic career at UAE University where he serves now as a Full Professor of Cell and Molecular Biology. His research focuses on ways to control cancer, particularly liver cancer. He published many research and review articles and serves as Reviewer and as an Editorial Member of many specialized peer-reviewed journals. He is also a member of many specialized societies and the sole recipient of many scientific awards.
Abstract:
Lecture about Crocin, one of the active ingredient of Saffron, exhibits anti-tumor, anti-proliferative, pro-apoptotic and anti-inflammatory properties against HCC.
Mr. Abdullah Abdulrahman Bin Salamah
King Saud University college of Medicine, Saudi Arabia
Title: Profile of viral hepatitis in Saudi Arabia
Time : 12:50-13:15
Biography:
Abdullah Abdulrahman Bin Salamah is a senior medical student at King Saud University, Riyadh, Saudi Arabia.
Abstract:
The study was conducted to investigate the profile of hepatitis in Kingdom of Saudi Arabia, and to determine which age group hepatitis viruses most commonly infect. The epidemiology of viral hepatitis in Saudi Arabia has undergone major changes, concurrent with major socio-economic developments over the last two to three decades. This disease represents a major public health problem in Saudi Arabia resulting in the need for considerable healthcare re-sources. A retrospective cross sectional analysis of the reported cases of viral hepatitis was conducted based on the reports of The Ministry of Health in Saudi Arabia about Hepatitis A, B and C infections in all regions from the period of January 2006 to December 2010. The study demonstrated that incidence of viral Hepatitis is decreasing, except for Hepatitis B that showed minimal increase. Of hepatitis A, B, and C, Hepatitis B virus (HBV) was the most predominant type, accounting for (53%) of the cases, followed by Hepatitis C virus (HCV) (30%) and HAV (17%). HAV infection predominates in children (5–14 years) with 60% of viral hepatitis cases, HBV in young adults (15–44 years) with 69% of viral hepatitis cases, and HCV in older adults (>45 years) with 59% of viral hepatitis cases. Despite significant changes in the prevalence of viral hepatitis A, B and C, it remains a major public health problem in Saudi Arabia; however it showed a significant decline in the last two decades that could be attributed to the vaccination programs and the improved health facilities. Further researches are needed to identify the risk factors making a specific age group or a specific region in Saudi Arabia targeted for a specific type of hepatitis viruses.
Dr. Fatma A Amer
Zagazig University, Egypt
Title: Hepatitis C virus burden in Egypt and efforts to combat
Time : 14:10-14:35
Biography:
Fatma A Amer is the past Head of Medical Microbiology and Immunology, and the current Supervisor of the Infection Control Program, Zagazig Faculty of Medicine, Egypt. She established her MSc degree in Infection Control in her university. She is the President of the Arab Alliance for the Prudent use of Antimicrobials and the Hepatitis Working Group, International Society for Chemotherapy. She has published more than 35 papers in national and international journals. She developed two parts of Infection Control books. She has attended more than 50 conferences all over the world. She has been aiding as a Reviewer, Editorial Board Member and Co-Editor in many national and international journals.
Abstract:
Egypt records the highest prevalence of HCV in the world; 14.7%. Explanations may be dated back to iatrogenic role of parenteral antischistosomal therapy campaigns. Other routes of infection are contributing to the ongoing HCV transmission. The prevalent genotype in Egypt is type 4. Risk factors for acquiring HCV infection include: History of antischistosomal injection treatment before 1986, old age, male gender, and residence in rural areas. Other risk factors include; injection therapy, blood transfusion prior to 1994, exposure to various facility-based medical procedures, and occupational transmission. In community settings, a set of risk factors mostly related to prevailing social and cultural conditions are responsible for maintaining the high rates of HCV transmission. Recent studies in Egypt documented that transmission might occur during family contact and sexual behavior. Chronic HCV is the main cause of liver cirrhosis and liver cancer in Egypt and indeed is one of the top five leading causes of death. Current HCV seroprevalence among children is also high, approximately 5-8%. Interest has emerged recently in Egypt in occult HCV infection. Many small scale studies have been performed which have highlighted the importance of this disease entity. Egyptian strategies to combat HCV are directed towards both prophylaxis and treatment. In the last 20 years several measures were applied to control HCV together with HBV. In 2006, the National Committee for Control of Viral Hepatitis (NCCVH) was formulated and in 2008 the Egyptian National Control Strategy for Viral Hepatitis was developed for aims of: Accurate determination of incidence and prevalence rates, reducing occurrence of infection by 20% by 2012 and conducting high quality research. In 2014, sofosbuvir was introduced in Egypt to be given with the standard care of therapy of HCV. Such combination will raise sustained virologic response to nearly 90%. To solve the problem of the very high cost of sofosbuvir, the Egyptian Government could make a deal with the manufacturer to have it at 1% of its price in USA. By applying all these measures we hope to reduce HCV infection down to 2% by year 2030.
Dr. Hussien Elsiesy
KFSH & RC, Saudi Arabia
Title: Improvement of hepatitis C related glomerulonephritis after kidney transplantation using sofosbuvir plus simeprevir
Time : 17:05-17:30
Biography:
Hussien Elsiesy has completed his MBBCh at Cairo University 1996. He had board certification in Internal Medicine 2001, Gastroenterology 2005 and Transplant Hepatology 2006. He served as Assistant Professor at Mount Sinai, NY 2006-2007 and currently as Clinical Associate Professor at Alfaisal University, Saudi Arabia. He was the Chairman of Department of Medicine 2008-2010, then the Chairman of Liver Transplantation Department 2010-2012 at KFSH-D Dammam, Saudi Arabia. He is the department Research Director as well as a member of Alfaisal University research committee.
Abstract:
Renal transplant (RT) recipients have a HCV infection rate of 5–15% in the developed countries, with higher rates in the developing world. The immunosuppressed state of RT recipients dramatically accelerated disease progression. This lead to severe HCV-related liver damage such as cirrhosis, fibrosing cholestatic hepatitis or liver failure. Liver disease is the fourth leading cause of mortality (8–28%) in long-term survivors after RT. Furthermore, HCV also negatively impacts renal graft survival. There is however very limited data on the use of direct acting antivirals (DAA) in patients with HCV post renal transplant. We report 69 year old lady, with history of hypertension, s/p living donor kidney transplant in 2004, with stable renal function (Creatinine was 0.74 until April 2014) presented with worsening renal function with creatinine reaching 5.4, Kidney biopsy (July & August 2014) showed no evidence of acute cellular or antibody mediated rejection (C4d negative), immune complex mediated glomerulonephritis (GN) likely related to HCV. Liver biopsy (August 2014): G-1, S 2-3 with 10% steatosis. HCV RNA 35, 451, 564 IU/ml, genotype 1a, P-ANCA, ANA were positive. The patient was treated with IVIG, Rituximab, Bortezumib, methylprednisone (500 mg x3), and total plasma exchange. Patient started on sofosbuvir and simeprevir without ribavirin for 12 weeks. HCV RNA at: Week 1: 1829 IU/ml, Week 2: <30 IU/ml, Week 4-8 and 12: undetectable, SVR 12: undetectable. Renal function dramatically improved with the last creatinine 1.2. In conclusion, the new DAA is highly effective in clearing HCV and resulted in dramatic improvement of HCV related GN.
Dr. Ehab Abd-El-Atty
Menoufia University, Egypt
Title: HBV: Challenges to cure in the future
Time : 14:35-15:00
Biography:
Ehab Abd-El-Atty has completed his PhD at the age of 35 years from Faculty of Medicine, Menoufia University, Egypt and Master degree of Medical Sciences from Faculty of Medicine, Catholic University, Leuven, Belgium. He is Professor of Internal Medicine, Hepatology and Gastroenterology, Faculty of Medicine, Menoufia University, Egypt. He has published more than 30 papers in reputed journals and has been serving as a Reviewer of Menoufia Medical Journal (MMJ). He is a member of AASLD (American Association for the Study of the Liver Diseases), ESGE (European Society of Gastrointestinal Endoscopy) and EASL (European Association for the Study of the Liver).
Abstract:
HBV is the second known carcinogen after smoking. Two billion worldwide had past HBV infection at a time. 350 millions have Chronic HBV. HBV has ten genotypes (A-J). Genotypes A and D have higher rates of chronicity than genotypes B and C. Genotypes C and D have high rates of cirrhosis and HCC as compared with genotype A and B. HBV may be presented as acute HBV or chronic HBV (Immune tolerant, HBe Ag+ve immune active, HBe Ag–ve immune active, carrier or occult). Egypt has 90% genotype D and 90% HBeAg –ve. Vaccination against HBV in infancy is the most effective approach to prevent HBV-related HCC. HBV patients should be screened for HCC every 6 month by US±AFP. Also each HBsAg-positive patients should be screened for anti-HDV. Goals of treatment of HBV are long-term suppression of HBV replication and decrease hepatic necroinflammation and fibrosis to prevent progression to cirrhosis and HCC. In the future, clearance of HBs Ag and cccDNA (covalently closed circular DNA). Candidates eligible for treatment according to are HBe Ag+ve or -ve immune active phases (PCR<2000 and elevated ALT or with moderate to severe liver inflammation), cirrhotic patients with PCR+ve, carrier and occult HBV with PCR+ve under immune suppression, acute fulminated HBV and decompensated cirrhosis. Candidates ineligible for treatment are immunotolerant, carrier and occult phases. Future strategies to eradicate HBV are targeting the host (immune therapy) and targeting the virus (inhibitors of cccDNA formation and inhibitors of HBV entry into the hepatocyte).
Dr. Tarek E Korah
Menoufiya University, Egypt
Title: Role of serum glypican-3 in the diagnosis and differentiation of small hepatocellular carcinoma from hepatitis-C virus cirrhosis
Time : 16:40-17:05
Biography:
Tarek Korah, is currently working as a Professor and head of Hepatology/Gastroenterology unit, Faculty of Medicine, Menoufia University, Egypt. He was a clinical research fellow of Newcastle University, U.K. He is a member of Egyptian-German association for the study of the liver. He published more than 35 papers in national and international peer-reviewed journals. Also, he served as a reviewer of Menoufia, and Alexandria Medical Journals, Egypt.
Abstract:
Background: Serum alpha-fetoprotein (AFP) has insufficient sensitivity and specificity for detection of hepatocellular carcinoma (HCC). Recently, glypican-3 (GLP-3) was suggested as a new biomarker for the detection HCC. Objectives: To determine the role of serum GLP-3 levels in the early diagnosis and differentiation of small (3 cm or less in diameter) HCC from liver cirrhosis. Also, to correlate GLP-3 levels to clinico-laboratory data. Methods: The study included sixty patients; 30 of them with hepatitis C virus (HCV) cirrhosis, and 30 patients with proved HCC. In addition, 20 healthy subjects were included as a control group. Clinical and radiological features (abdominal ultrasonography and/or abdominal triphasic computed tomography) were recorded. Liver function tests, complete blood cell count, and serum AFP were measured. Serum GLP-3 values were determined by an ELISA technique. Results: Serum levels of GLP-3 were significantly elevated in patients with HCC compared with HCV cirrhosis group (p<0.001). Also, these levels were significantly elevated in these two patients’ groups versus controls (p<0.001). Also, serum GLP-3 levels with cut-off value of ≥240 ug/L had a higher sensitivity (100%) and same specificity (93.3%), than AFP with cut-off value of ≥200 ng/ml, for detection of HCC. Moreover, GLP-3 levels showed a higher sensitivity than AFP (50% vs. 41.7%), for detection of small HCC. The combined use of both markers (i.e. when either one of the two markers positive) improved the specificity to 88.9%. Regarding unicentric HCC, GLP-3 at cut-off value of ≤580 ug/L had better specificity than AFP at cut-off value of ≤765 ng/ml (57.1% vs. 42.9%). The combined use of both markers improved the sensitivity and specificity to 82.6% and 71.4%, respectively. Conclusion: Serum GLP-3 levels are higher in HCC versus HCV cirrhosis, which can differentiate HCC from liver cirrhosis. Also, serum GLP-3 is highly sensitive and specific for detecting HCC. Moreover, GLP-3 is more sensitive than AFP for the detection of small HCC. Furthermore, a combination of both serum markers yielded an improved specificity and both sensitivity and specificity for the diagnosis of small and unicentric HCC, respectively.
- Poster Presentations
Location: Prestwick
Session Introduction
Ekaterina Liusina
I.M. Sechenov First Moscow State Medical University, Russian Federation
Title: Transient elastography-based model for assessment of portal hypertension in patient with HCV and alcohol-related liver cirrhosis
Biography:
Ekaterina Liusina is currently a PhD fellow in Gastroenterology. Her professional interests include Portal hypertension, Viral hepatitis, Liver cirrhosis and Statistical methods in medicine. She is the member of Russian Scientific Liver Society, Russian Gastroenterology Association and European association for the study of the liver.
Abstract:
Background: Elimination of the etiological agent responsible for the progression of chronic liver injury has been shown as one of the important prognostic factor for survival in cirrhotic patient. Portal hypertension is a main complication of liver cirrhosis. Measurement of hepatic venous pressure gradient (HVPG) is currently recommended for detection of portal hypertension but its wide use in the clinical practice is limited by its expensiveness and invasiveness. Colecchia et al. in 2012 published predictive model for HVPG values included spleen (SS) and liver stiffness (LS) measured by transient elastography in cohort of patients with HCV-related liver cirrhosis. Aims: To establish the prognostic predictive value of HVPG model (calculated with SS and LS) for presence of esophageal varices and risk of bleeding. To evaluate clinical significance of spleen and liver stiffness measurements in 3 cohort of patients: HCV-related cirrhosis before and after antiviral treatment, HCV-related liver cirrhosis follow-up and in patients with alcoholic cirrhosis before and after period of abstinence. Methods: We plan to enroll consequently in the study one hundred patient with HCV and alcohol-related cirrhosis. Patients undergo baseline blood test sampling, upper endoscopy for detecting esophageal varices, ultrasound, liver stiffness measurement with Fibroscan (LS), spleen stiffness measurement with Fibroscan (SS) during a week of hospitalization. HVPG calculates according to predictive model HVPG =-4.44+0.241LS+0.226Ñ…SS. For all patient with alcoholic cirrhosis will be given recommendation for abstinence. HCV-patient who will meet inclusion criteria will be treated in clinical trials with different antiviral regimes. All baseline procedures will be repeated in 6-12 month after baseline. Complication during follow-up period will be registered. At the moment enrolled 41 patients (26 patients with HCV – related cirrhosis, 15 patients with alcoholic cirrhosis) Results: LS and SS in the group with varices are significantly higher than without (p=0.003). Median of LS in varices group is 32.4 kPa (IQR 24.8-48) vs. 20.6 kPa (IQR 16.9 – 27.5). Median of SS in varices group is 58.2 kPa (IQR 38.6-75) vs. 36.3 kPa (IQR 29.4-63.9). Levels of portal pressure calculated with predictive model are significantly higher: in varices group (p=0.009) is 16.8(IQR 11-23) vs. 9.4 (IQR 7-13) respectively. Sensitivity HVPG predictive model for detection EV is 92%, specificity is 61%. For predicting esophageal varices in our group (regardless etiology) PPV is 83%, NPV is 80%, LR+ 2.3, LR-0.14 respectively. In addition a statistically significant difference is observed when compare patients with alcohol-related cirrhosis (median LS is 45,4kPa (IQR 25-75) to HCV-related group (median LS is 24 kPa (IQR 16-27) (p=0.004). Conclusion: We plan to investigate the diagnostic test accuracy of HVPG predictive model for esophageal varices depending on the etiology of liver cirrhosis (HCV or alcohol) in separate.
Dr. Shi-Bing Su
Shanghai University of Traditional Chinese Medicine, China
Title: Discovery of potential biomarkers from chronic hepatitis B to cirrhosis by cytokine profiling analysis
Biography:
Dr. Shi-Bing Su, Medicine Doctor (Ph.D.-medicine), is a Professor of Integrative Medicine and Traditional Chinese Medicine (TCM), director of the center for complex systems, Shanghai University of TCM, leading scientist of TCM System Science Discipline, distinguished researcher of Shanghai TCM internal Medicine E-institute, visiting professor of Nanjing University of TCM, guest professor of Henan college of TCM, academic Journal editor for Integrative Medicine International, Journal of Integrative Medicine, Journal of TCM Science, etc. He got his B Sc in TCM at Nanjing University of TCM, M Sc in Pharmacy and Medicine Doctor degree in Gastroenterology at Cancer Institute, Kanazawa University, and Docent at China Pharmaceutical University. Currently Dr. Shi-Bing Su research focus on TCM syndrome classification-based treatment in clinical and basic studies applied by system biology. He has published 160 papers and 10 books in academic Journals.
Abstract:
Background: Liver cirrhosis is a critical state in the natural course of hepatocellular carcinoma (HCC). Chronic hepatitis B (CHB) is a major cause of liver cirrhosis in China. To find biomarkers for the diagnosis of CHB caused cirrhosis (HBC), we examined the cytokines profiling of CHB and HBC. Methods: Serum samples of 15 health controls (HC) and 15 CHB patients and 15 HBC patients were collected to detect the profiles of 48 cytokines by multiplex biometric ELISA-based immunoassay. Partial least squares discriminant analysis (PLS-DA) was used to analyze the significant cytokines, and they were validated using independent cohort of 60 CHB patients, 60 HBC patients and 35 HC samples. Results: There were 22 differential expressed cytokines of CHB and HBC. Three differential expression cytokines including interleukin (IL)-9, IL-2 receptor subunit alpha (IL2Rα) and Granulocyte-macrophage colony-stimulating factor (GM-CSF) were found by PLS-DA, and their significant changes of serum levels were further validated. The Receiver-operator characteristic (ROC) analysis demonstrated that three cytokines and their logistic regression panel potentially to be the potential biomarkers for CHB and HBC differentiation (P<0.001, AUC=0.876). Furthermore, a functional pathway analysis showed that differential regulation of cytokine production in macrophages, T Helper Cells and intestinal epithelial cells by IL-17A and IL-17F were enriched in the 22 differentially expressed cytokines. They were also enriched in pathway of hepatic fibrosis / hepatic stellate cell activation. Conclusions: There were particular cytokines profiles of CHB and HBC. Besides, IL-9, IL2Rα and GM-CSF may be involved in the differentiation of CHB and HBC.These findings may give further insight into the pathobiology of HBC.
Dr. Chiou-Hwa Yuh
Institute of Molecular and Genomic Medicine, ROC
Title: Establishment of anti-hepatocellular carcinoma drug screening platform in zebrafish
Biography:
Chiou-Hwa Yuh has completed her PhD from National Yang-Ming University in Taiwan, and Postdoctoral studies from California Institute of Technology in USA. She was famous in Developmental Gene Regulatory Networks. She initiated the systematic analysis of hepatocellular carcinoma (HCC) in mouse model, and established transgenic zebrafish model. She further developed the drug screening platform to identified novel small molecules which are effective in treatment HCC and lower toxicity compared to Sorafenib. She has published 41 papers in reputed journals and has been serving as an editorial board member of repute journals.
Abstract:
The formation of hepatocellular carcinoma (HCC) is a chronic progress including hepatitis, steatosis, fibrosis, cirrhosis. Liver cancer is the third most common cancer worldwide and ranked as a leading cause of mortality in Taiwan. Traditional chemotherapy and radiation has poor effectiveness for the treatment of liver cancer patients, for the target therapy, Sorafenib is the only one approved by FDA which can inhibit liver cancer and prolong life. The development of new target therapy is therefore urgently needed. Previously, we have used the HBx-induced HCC mouse model and identified four common regulators (Src, Edn1, Bmp4 and Bmp7) which can be used as molecular targets for HCC treatment. Furthermore, we have established the transgenic fish overexpressing HBx or src in the p53 mutant, and edn1 transgenic zebrafish developed into HCC. Those transgenic fish developed steatosis, hepatitis, fibrosis before cancer formation. The HCC from those transgenic zebrafish is much more similar to human HCC in histopathology or the pattern of gene expression, which allow them more suitable as drug screening platform to identify the drugs to effectively treat human liver cancer. In this report, I will demonstrate the advantage of zebrafish HCC model as well as zebrafish embryos. We have developed a high-throughput drug screening platform to identify novel and safe anti-HCC therapeutic means to save more life. In addition, due to the heterogeneity of HCC, there are no effective clinical tests that can predict the effectiveness of the anti-cancer agents for patients. Using patient-derived xenograft zebrafish model, we are able to identify personalized medicine for the future use in clinical therapy.
Dr. Maha Hussein
Ain Shams University, Egypt
Title: Salivary pH as an indicator for hepatocellular carcinoma
Biography:
Maha Mohsen Hussein is currently working as an Assistant Professor of Hepatology and Gastroenterology, Ain Shams University. Graduated with honor in 1998 from Faculty of Medicine, Ain Shams University. Had Master Degree in 2002 with a research on (Relationship between Gastric and Gallbladder Empting in Patients with Non Ulcer Dyspepsia Positive for Helicobacter Pylori) and MD Degree in 2007 completed by research on (Relation between aflatoxin B1 level and glutathione antioxidant in chronic hepatitis C patients with and without hepatocellular carcinoma). Worked since graduation in Ain Shams University; Residency then Assistant lecturer at 2003, Lecturer at 2007 and Assistant professor since 2012 till now. Joined liver transplantation team of Ain Shams Hospitals since 2008 till present as transplant hepatologist and had observer ship in the Transplantation Center of Methodist Hospital in Texas in USA 2009. Worked as a member of national team for prevention and treatment of viral hepatitis 2007-2010.
Abstract:
Reports in recent years have indicated that saliva represents an increasingly valuable resource for disease diagnostics including periodontal diseases as well as different types of cancer, cardiovascular, endocrine, immune and hereditary diseases. In contrast to blood pH which is under tight control, salivary pH shows variability depending on a wide range of factors reflecting its potential variability in chronic health status. In this study, we investigated the potential role of salivary pH to reflect the state of chronic metabolic acidosis in patients with hepatocellular carcinoma. Salivary pH was measured in 300 subjects using narrow range pH strips. Subjects were divided into 3 groups, group I consists of 100 healthy volunteers, group II consists of 100 patients with liver cirrhosis and group III consists of 100 patients with HCC. Results showed a significant difference (P≤0.05) in salivary pH values between the three groups with the HCC group being the most acidic (mean value of 5.62) followed by the cirrhotic group (mean value of 6.24). The control group showed normal salivary pH (mean pH value of 6.6). The predictive performance of salivary PH as an indicator of hepatic malignancy among the 100 patients of HCC shows that the salivary pH level at a cut off value of ≤5.85 gives a sensitivity of 80% and a specificity of 84%. The non invasive and economically sound nature of this test makes it a potential auxillary test in screening for HCC.
Dr. Tari Magdy George Michael
Ain Shams University, Egypt
Title: Study of factors contributing to persistent thrombocytopenia following liver transplantation
Biography:
Tari M.A. George Michael is currently working as an Assistant lecturer in Ain Shams University in the department of Gastroenterology and Hepatology. Graduated from faculty of medicine, Ain Shams University in 2006 with honors, worked as a resident in Ain Shams University hospitals till 2012 then promoted to Assistant lecturer in the same university in 2013. Completed her Master's degree in 2011 with honors with a research on the "Hemostatic changes in liver cirrhosis". Completed 2 parts of the MRCP certificate in Internal medicine. Completed first part of the MD and a thesis on "Factors affecting platelet count after liver transplantation", and preparing for the final part of the MD. Took part in the endoscopy training in association with Hull University in UK and is currently in the Ain Shams University center for endoscopy.
Abstract:
Thrombocytopenia is one of the common features of advanced liver cirrhosis. Liver transplantation is the only treatment for end stage liver disease, but even after transplantation thrombocytopenia is frequent. The aim of this study was to monitor platlets count and to identify factors contributing to persistence of thrombocytopenia following liver transplantation. The study included 36 patients who underwent LDLT in Ain Shams Center of Organ Transplantation (ASCOT) in one year (2013). Preoperative platelet count was recorded. Following transplantation, platelets count was recorded daily for the first two weeks, then at one month, 3 months, 6 months and 12 months. Splenic size and portal venous blood flow was measured at the same intervals by Doppler ultrasound. Thrombopoietin was measured before surgery then at 2 weeks and 6 months following transplantation. Persistent thrombocytopenia was defined as a platelet count less than 150 x 109/L at one year post-transplantation. At the end of the study, 56% of patients had persistent thrombocytopenia at 1 year. Factors that showed significant correlation with persistent thrombocytopenia were lower preoperative platelet count, lower preoperative portal vein flow velocity, greater preoperative spleen size, higher GRWR and longer operative time. Highest sensitivity was found for preoperative portal flow velocity and highest specificity was to GRWR. HCV recurrence, rejection episodes, CMV infection, biliary and vascular complications post operative were not independent factors for persistent thrombocytopenia.