Day 1 :
Columbia University, USA
Maxwell Chait is a Fellow of the American College of Physicians, American College of Gastroenterology, American Gastroenterological Association and the American Society for Gastrointestinal Endoscopy. He is a Practicing Gastroenterologist and is an Assistant Professor of Medicine at the Columbia University, College of Physicians and Surgeons in New York City. He has authored numerous publications in reputed journals. He is the Editor-in-Chief of the Journal of Liver Disease and Transplantation and serves on the Editorial Board of the World Journal of Gastrointestinal Endoscopy.
Lower gastrointestinal bleeding (LGIB) is an important cause of morbidity and mortality in patients with cirrhosis. It occurs in approximately 20% of all patients who present with gastrointestinal bleeding (GIB) with cirrhosis. Gastrointestinal diseases that cause LGIB in patients with cirrhosis include specific vascular diseases, inflammatory diseases and bowel ischemia. However, in patients with less severe cirrhosis and advancing age, the causes are much like the general population and must also be considered. The incidence and severity of LGIB in patients with cirrhosis depends upon the incidence of specific gastrointestinal diseases, coagulopathy, co-morbid diseases and polypharmacy. The evaluation and treatment of patients is adjusted to the rate and severity of hemorrhage and the clinical status of the patient and may be complicated by the presence of visual, auditory and cognitive impairment due to hepatic encephalopathy. Bleeding may be chronic and mild or severe and life threatening, requiring endoscopic, radiologic or surgical intervention and methods to reduce portal hypertension.
Fondazione IRCCS - National Cancer Institute, Italy
Arnolfo Petruzziello is the the Head of the Virology and Molecular Biology Unit at National Cancer Institute, IRCCS Fondazione G Pascale in Naples, Italy. He has done his Post-graduation in Microbiology and Virology, and PhD in Molecular and Cellular Pathology. He has done his Post-doctoral studies from the University Federico II of Naples. He is a Reviewer and Editorial Board Member for several international scientific journal and conferences.
Background: Different hepatitis C virus (HCV) genotypes exhibit differences in disease pathogenesis and progression, as well as in disease outcomes and response to therapy. Tracking the change of HCV genotypes in various epidemiological settings is critical for both disease surveillance and the development of improved antiviral treatment. Here, we tracked the changes in the prevalence of the distribution of HCV genotypes in Southern Italy in three different periods 2006-2008, 2009-2011 and 2012-2014.
Materials & Methods: HCV genotypes distribution was analyzed in 535 HCV-RNA positive patients with chronic HCV infection, observed from 2012 to 2014, and compared with our previous study, which recorded data in the period 2006-2008 and 2009-2011. Pearson Chi-square test and t-test were used to statistically analyze the results.
Results: In all the periods analyzed, genotype 1 is predominant, even if its prevalence decreased from 2006 to 2014 (64.3% in 2006-08, 62.4% in 2009-11 and 60.8% in 2012-14). On the contrary, in the same period, the genotype 2 prevalence increased (27.9% in 2006-08, 31.7% in 2009-11 and 35.2% in 2012-14), whereas genotype 3 seems to show a decrease during the time (6.8% in 2006-08, 4.7% in 2009-11 and 3.2% in 2012-14). Subtype 1b, particularly common in females compared to males in the past (64.3% vs. 39.3% in 2006-08, p<0.001 and 54.0% vs. 41.5% in 2009-11, p<0.05), seems to be now quite equally distributed between males and females (52.7% vs. 56.6%). Instead, the male/female ratio for genotype 3 is highly decreased from 2006 to 2014. The prevalence of patients with genotype 1b in the age range 31-40 years is significantly higher in the 2012-14 period than in both previous periods (53.8% vs. 16.6% in 2009-11, p<0.001 and 13.4% in 2006-08, p<0.001) and lower in the over-60-year-olds (57.9% vs. 59.6% in 2009-11 ).
Conclusions: Genotype 1b, historically the most prevalent in Southern Italy, is still predominant; however, when comparing the three time periods, genotype 2 seems to show an increase in the general population not related to age or gender, whereas genotype 1b, even if the most common in the elder population, shows a significantly increase in the under 40 years old population.
- Track 5: Hepatitis Vaccination
Track 8: Liver Diseases
Location: Park Inn by Radisson London Heathrow
University of Oxford, UK
Bevin Gangadharan is a Research Associate in the Oxford Antiviral Drug Discovery Unit, University of Oxford headed by Professor Nicole Zitzmann. The main focus of his current research is to use proteomics to identify and validate novel serum biomarker candidates for NAFLD. He carried out his DPhil with Professor Nicole Zitzmann where he identified serum biomarker candidates for liver fibrosis in hepatitis C patients.
Background & Aim: Liver biopsy is the reference standard for NAFLD diagnosis and staging. NAFLD can be assessed less invasively using immunoassays to detect serum biomarkers. However, biomarkers can degrade due to sample storage conditions and therefore may not be detected using these antibody-based assays. Detection of biomarkers by mass spectrometry (MS) overcomes this disadvantage.
Methods: MS and two dimensional gel electrophoresis (2DE) were used to find differences in the abundance of proteins among serum samples from patients with varying NAFLD and fibrosis stages (NAFL, NASH F0, NASH F1, NASH F3 and healthy individuals). The identified proteins are potential NAFLD biomarkers. Mass spectrometry was used to assay for biomarkers by detecting their tryptic peptides and fragments. We are the first and only lab to use a novel quantitation method with clinical samples. Unlike current liver disease biomarker tests, our approach is the only biomarker assay using a universal calibration mix.
Results: Using MS and 2DE, we identified several potential biomarkers for NAFLD which were checked by both targeted MS and Western blotting using serum from patients with varying stages of NAFLD. Our novel biomarkers look promising when compared to cytokeratin-18 and the protein markers used in NashTest. A mass spectrometry assay was developed for the most promising novel liver fibrosis biomarkers.
Conclusion: We are working towards the first ever antibody-free biomarker assay for NAFLD. Our assay is nine times faster than conventional quantitation by MS making our approach for absolute biomarker quantitation applicable for clinical use. In all current liver disease biomarker assays, different calibrations curves are required for each biomarker with each point on the curves being read separately and samples could be analyzed several hours after establishing a calibration curve by which time there is the possibility of instrument drift. Our assay overcomes these disadvantages since it is the only assay which can analyze all points of the calibration curve and determine the absolute concentration of the NAFLD biomarker in a single acquisition. Our assay may help reduce the need for invasive liver biopsies in NAFLD patients.
Chinese University of Hong Kong, Hong Kong
Terence T Lao is a specialist in Obstetrics, Gynaecology and Maternal-Fetal Medicine. He has received training in Hong Kong; London, UK; and Canada. He is currently a Professor in the Department of Obstetrics and Gynaecology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. His clinical and research interests are oriented around maternal medicine, especially endocrine and hepatic problems, hypertension, and hepatitis, as well as the management of high risk pregnancy. He is a reviewer of many international journals, and serves on the Editorial Board of three. He has 442 publications, including abstracts, listed under Google Scholar.
The hepatitis B vaccine has been in use for more than three decades and its efficacy has been widely reported. In Hong Kong, excellent vaccine coverage through an efficient public health care system, together with supplemental programs and easy availability of the vaccine, meant that most young pregnant women, and university students at entrance, should have been protected. Yet data from Hong Kong has not indicated a progressive decline in maternal carriage of hepatitis B virus (HBV). On the other hand, significant increase in the prevalence of HBV infection and a positive correlation with age has been found in students at university entrance, and in young mothers aged 25 years or less. This paradoxical phenomenon is most likely related to clinical vaccine failure. A number of factors are involved, such as the failure to respond to a primary series of hepatitis B vaccination in infancy, the waning of antibody titres with age, and loss of anamnestic response in a significant portion of the vaccines. We have shown that up to one in five of children who had received a full course of hepatitis B vaccination in infancy failed to develop an immune response. Furthermore, among adolescents and young adults covered by the universal vaccination program in infancy, waning of antibody titres to non-protective levels and loss of anamnestic response are not uncommon by the time of university entrance, despite a low incidence of HBV infection. Taken together, there is concern for the purported life-long protection conferred by hepatitis B vaccination in infancy. The duration of protection should be re-examined in further studies and remedial measures considered if long term protection is found to be insufficient. Otherwise, the efforts to control HBV infection, especially in high endemicity regions, with universal vaccination in infancy would be rendered futile.
Taipei Medical University, Taiwan
S C Yang is a Professor in the School of Nutrition and Health Sciences, Taipei Medical University. She has worked on the relationship between nutrition and alcoholic liver diseases.
Background: Impaired homocysteine metabolism plays an important role in alcoholic liver disease (ALD); however, there are limited data about its relationship with the risk and severity of patients with ALD in Taiwan.
Participants & Methods: To understand plasma homocysteine and related vitamin concentrations in patients with ALD in Taiwan, we recruited 50 male patients with ALD from Cathay General Hospital, with 49 age-and gender-matched healthy adults as the control group. The Institutional Review Board for Human Studies approved the study, and informed consent was obtained from all patients prior to blood collection.
Results: Significantly higher plasma homocysteine concentrations but lower folate concentrations were obtained from patients with ALD. In addition, patients with ALD showed a significant lower erythrocyte reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio but higher plasma thiobarbituric acid-reactive substance (TBARS) concentration, which indicated that oxidative stress was occurring in patients with ALD. A negative correlation between plasma folate and homocysteine was observed in all subjects. There was also a negative correlation between plasma homocysteine and the erythrocyte GSH/GSSG ratio which indicated impaired homocysteine metabolism may have disrupted the antioxidative status. In addition, patients in Child-Pugh class B and C showed higher plasma vitamin B12 concentrations than did patients without cirrhosis and patients in Child-Pugh class A.
Conclusion: These findings show that impaired homocysteine metabolism was observed in patients with ALD in Taiwan. In addition, the plasma vitamin B12 concentration may reflect the degree of liver injury.
China Pharmaceutical University, China
Lulu Xu is doing her PhD in Life Sciences from the School of Life Science and Technology, China Pharmaceutical University. Her research work focuses on liver diseases. She has done her Bachelor's degree from China Pharmaceutical University, China.
Liver is an important metabolic organ, which is usually attacked by various toxic substances, such as bacteria, viral hepatitis, alcohol and hepatotoxic drugs. ALF, characterized by a sudden large area of inflammation and extensive hepatocyte death, is defined as a life-threatening disease with a high mortality rate. Although many drugs are commercially available to ALF, there are still no ideal therapeutic methods. Berberine (BBR), an isoquinoline alkaloid extracted from Chinese herb Rhizoma Coptidis, has several pharmacological activities. The study was aimed to investigate the effect of BBR on ALF in vivo and in vitro. Mice were administered intraperitoneally with BBR (5, 10 and 15 mg/kg/d) and orally with silymarin (200 mg/kg/d) for 3 days prior to an injection of D-Galactosamine (D-GalN)/lipopolysaccharide (LPS). The mortality and liver damage were subsequently evaluated. The results showed that BBR attenuated D-GalN/LPS induced liver damage, as evidenced by the reduction of mortality, the alleviation of liver pathological changes and the down-regulation of alanine aminotransferase (ALT)/aspartate aminotransferase (AST). Additionally, BBR exerted anti-oxidant capacity with the rise of hepatic glutathione (GSH) in ALF. The data also exhibited that BBR suppressed D-GalN/LPS induced the nuclear translocation of NF-κB p65 and the expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) at mRNA and protein levels. In vitro, human L02 hepatocytes injury was stimulated by D-GalN (5 mM)/TNF-α (100 ng/ml) and the cell apoptosis was improved by pre-incubation with BBR. Western blotting showed that BBR effectively suppressed apoptosis via modulating bax/bcl-2 rate, cytochrome c release and caspase-3/-9 cleavage. In summary, we concluded that BBR may be a potential strategy for the treatment of ALF. Our findings demonstrated that the hepatoprotective property of BBR was relied on inhibiting inflammation and apoptosis in ALF.
Mansoura University, Egypt
H Hakim has his expertise in Evaluation and Management of Hepatic Diseases in Egypt Mansoura Faculty of Medicine. He has worked as a Resident in the Internal Medicine department at Mansoura University Hospital. Currently, he is working as an Assistant Professor of Hepatogastroenterology.
Objectives: To compare between procalcitonin and C-reactive protein regarding diagnosis of spontaneous bacterial peritonitis (SBP).
Study Design & Setting: This is a case control cross sectional study carried out at the Hepatology and Gastroenterology Unit, Specialized Medical Hospital, Mansoura University Hospital.
Participants: In this study, 162 patients admitted to Hepatology and Gastroenterology Unit from January 2014 to January 2015, complaining of liver cirrhosis and ascites were considered.
Methods: Blood samples were withdrawn from all subjects involved in the study and used for complete blood count, INR, serum creatinine, albumin, bilirubin, liver enzymes, serum CRP and PCT. Ascitic fluid samples (20 ml) were withdrawn under complete aseptic technique and analyzed for polymorph nuclear leukocyte count, glucose, protein, lactate dehydrogenase (LDH), and culture (causative organism and antibiotic susceptibility testing).
Results: The cut-off point of serum PCT at which SBP can be diagnosed was 495 pg/ ml with sensitivity and specificity of 90% and 92%, respectively. The cut-off point of serum CRP at which SBP can be diagnosed was 10.5 mg/L with sensitivity and specificity of 91% and 97%, respectively.
Main Outcome Measures: Specific diagnostic impact of tests.
Conclusion: Serum procalcitonin and CRP are good indicators of SBP but serum CRP is more sensitive and specific in comparison with PCT as a predictor for SBP.