Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 2nd International Conference on Hepatology Chicago, Illinois, USA.

Day 3 :

Keynote Forum

Anil Kaul

Oklahoma State University, USA

Keynote: Microflora and TLRs in HCV-related cirrhosis and hepatocellular carcinoma

Time : TBD

Conference Series Hepatology 2016 International Conference Keynote Speaker Anil Kaul photo
Biography:

Anil Kaul MD, DDS, MPH graduated from Madras Medical College in Medicine, King Georges’ Medical College in Dentistry, and in Public Health from University of Minnesota. He currently serves as Director of High-Complexity Clinical Laboratories and a Faculty at Oklahoma State University-Center for Health Sciences. He has been awarded 6 Patents and has published more than 50 scientific papers. He has served as senior health advisor to the US Department of State and received “Expeditionary Service Award”. In 2014, he also received “Lifetime Achievement Award” at Global Health Summit, and in 2008 he was named as Sony’s “Scientist of the Year Award”.

Abstract:

Chronic Hepatitis C virus (HCV) infection can lead to hepatocellular carcinoma (HCC). We recently reported presence of bacteria in normal and cirrhotic liver tissues and investigated Toll like receptors (TLR) activation of HCV-related cirrhosis and HCC. Aberrant expression or activation of TLRs results in chronic inflammation that can promote carcinogenesis. We hypothesize that changes in liver microbiome can result in altered TLR expression that influences HCV-related cirrhosis and carcinogenesis. Therefore in this study, we investigated bacterial flora and expression of TLR2 and TLR4 in normal liver tissues, HCV-related cirrhotic tissues and HCV-related HCC tissues. Tissue sections were stained for TLR2 and TLR4 expression by immunohistochemistry and the staining intensity was quantified. Gram-positive and Gram-negative organisms were present in all the liver tissues. There were no changes in the expression of TLR2 among the different study groups. TLR4 expression was reduced in HCV-cirrhotic and HCV/HCC hepatocytes compared to normal liver hepatocytes. Lower TLR4 expression in cirrhotic and HCC tissues could be due to altered microbial flora and reflect increased innate immune suppression during cirrhosis and cancer development. These findings suggest that microbial ecology might contribute towards immunosuppression of TLR4-mediated innate immunity in cirrhotic livers undergoing progression to HCC. Manipulating bacterial ecology or TLR4 agonist treatment could prevent HCV-related liver cancer development.

  • Track 4: Liver Diseases
    Track 10: Bile formation and Related Diseases
Speaker
Biography:

Mathieu Vinken has a background in pharmaceutical sciences and holds a PhD in experimental hepatology. He is a Professor and registered toxicologist at the Free University Brussels, Belgium. His research interests are situated in the field of connexin and pannexin research and its relevance for the areas of toxicology and hepatology. He is author of more than 100 publications. He is a regularly invited speaker on international conferences and acts as reviewer for several scientific journals. He is a member of 5 scientific societies in the field of toxicology and is Vice-President of the European Society of Toxicology in Vitro.

Abstract:

Gap junctions, which mediate intercellular communication, are key players in liver homeostasis. As a consequence, they are also frequently involved in liver pathology. This equally holds true for connexin hemichannels, the structural precursors of gap junctions, and pannexin channels, connexin-like proteins assembled in a hemichannel configuration. Both connexin hemichannels and pannexin channels facilitate extracellular communication and drive a number of deteriorative processes, such as cell death and inflammation. Connexins, pannexins and their channels underlie a wide spectrum of liver diseases, including acute liver failure, cholestasis, hepatitis, steatosis, liver fibrosis and cirrhosis. This could open promising perspectives for the characterization of new targets for therapeutic purposes in the area of hepatology. This will be demonstrated in this presentation using data generated in my group in the last 2 years. It will be specifically shown that pharmacological inhibition of connexin hemichannels and pannexin channels counteracts the clinical manifestation of acetaminophen-induced acute liver failure and diet-induced non-alcoholic steatohepatitis in mice.

Speaker
Biography:

H E Liu received her PhD from University of Illinois at Chicago. She is a Professor at School of Nursing, College of Medicine, Chang Gung University, Taiwan. Y F Lin received her MS from School of Nursing, College of Medicine, Chang Gung University, Taiwan. She is a commissioner at the Nursing Management Department, Chang Gung Memorial Hospital, Taiwan.

Abstract:

This is a cross-sectional survey that 128 liver transplanted patients were recruited from OPD in a medical center at northern Taiwan. We collected the information related to self-care knowledge and behaviors, health locus of control, and personal information (included demographic and medical related variables) by questionniares. Results of descriptive statistics showed that subjects were charterized as: male (81.3%), married (81.3%); senior high school educated (32.8%); and Buddhist (48.4%). Their mean age was 52.1 years (SD=8.74; rnage: 20-72 years). In regard to employment, 19.5% were unemployed prior liver transplantation. After transplantation, 38.3% returned to work, and 4.7% changed their work, and 20.3% returned to work within 6 months. Before transplantation, their major diagnosis was B-hepatis (35.2%), hepatoma (25%) and terminal stage of liver cirrhosis (21.9%). Mean duration since transplantation was 3.24 years (SD=2.68; range: 0.37-15.92 years). Most of the transplantation were done in Taiwan (94.5%). 77.3% of the subjects experienced complication after transplantation, such as rejection, bile duct illness, and infection. The correct rate towards knowledge of self-care was 69.4%, indicating a moderate level of knowledge. The frequency of performing self-care hehaviors was 81.5%. The results of stepwise regression found that knowledge level of self-care could be ptrdicted by: duration since transplantion, age, and health locus of control (R2=21.8%). In addition, years of education, income higher than 40000NT/month(US$1333), age, and has religion were the predictors of self-care behaviors (R2 = 24.2%). Clinical implications were discussed within the text.

Speaker
Biography:

Junseo Oh has completed his PhD from Kyoto University and Postdoctoral studies from NIH/NCI, MD. He is currently working as a Professor in the Department of Biomedical Science, Korea University Graduate School. His research interests include extracellular matrix remodeling, tumor invasion and tissue fibrosis.

Abstract:

Liver fibrosis is the excessive accumulation of extracellular matrix including collagen. Activated Hepatic Stellate Cells (HSCs) are major producer of fibrotic neomatrix, playing a key role in the fibrogenesis and inactivating HSCs has been considered a promising therapeutic approach. We previously showed that albumin is endogenously expressed in quiescent HSCs and that its expression inhibits HSC activation. For stellate cell targeting, albumin (domain III) was fused to C-terminus of Retinol Binding Protein (RBP) and the resulting recombinant fusion protein (referred to as R-III) was found to be incorporated into cultured HSCs in a STRA6 (a membrane receptor for RBP) dependent manner and inactivate HSCs. Our mechanistic study showed that Retinoic Acid (RA) signaling is involved in HSC activation and that R-III treatment or albumin expression down regulates its signaling through direct binding to RA, which likely contributes to the anti fibrotic effect. RA receptor agonist and retinaldehyde dehydrogenase overexpression abolished the anti fibrotic effect of R-III and albumin respectively. In animal experiments, injected R-III via tail vein was found to be localized predominantly in HSCs in liver indicating that RBP functions as a targeting domain. Importantly, R-III administration reduced liver fibrosis induced by carbon tetrachloride (CCl4) or bile duct ligation (BDL) by 35%, which was accompanied with decreased immunostaining of α-smooth muscle actin, a marker of myofibroblasts. It also exhibited a preventive effect against CCl4 inducd liver fibrosis. Our in vitro studies, together with our in vivo observations suggest that R-III is a good candidate as a novel anti fibrotic drug.

Speaker
Biography:

Reda M El Badawy has completed her MD at Banha University, Faculty Medicine. She is working at King Saud University and King Khaled University, Saudi Arabia. She has published more than 25 papers in reputed journals.

Abstract:

Background: Hepatorenal syndrome (HRS type 1, 2) is one of the serious complications of chronic liver disease with high mortality. Aim: The aim of this study was to evaluate the diagnostic role of urotensin II in patients with chronic liver diseases (both ascitic and non ascitic patients). Forty patients were selected, Group (1) 20 patients with ascites (9 males and 11 females). Group (2) 20 patients without ascites (8 males and 12 females) and with their age and sex matched. Results: For ALT, T.B, DB, serum urea and platelet count, there was a statistically significant decrease between the 2 groups (p<0.05). The ultrasound findings of the kidneys were of statistically significant difference between the two groups as regard nephropathy (8 patients in ascitic group [1] while one patient in non ascitic group [2]) (p value <0.05). There was a statistically significant correlation between Urotensin II and blood urea level in group 2. The cut-off value of Urotensin II was of sensitivity 66.7%, specificity 64.5%, PPV 35.3% and NPP 86.96% with Accuracy 59% and p value <0.42 of no statistically significant difference. Conclusion: Urotensin II was of statistically significant positive correlation with blood urea level in patients without ascites that means the relevant clinical importance to use urotensin II in the early stages of liver disease that is of crucial prognostic important for follow up.

Speaker
Biography:

Ho Gak Kim has completed his MD from Kyungpook National University School of Medicine, Taegu, South Korea. He is the Chief Physician at Catholic University of Daegu School of Medicine, Daegu, South Korea since 2013. He has published more than 100 papers in reputed journals and has been serving as a President of Korean Pancreaticobiliary Association since 2014, and Editorial Board Member of Clinical Endoscopy.

Abstract:

Introduction: Pancreatic cancer is among the most common cancers associated with pulmonary thromboembolism (PTE). Moreover, PTE has developed in patients with thrombocytopenia as well as thrombocytosis during gemcitabine-based chemotherapy. Aim: The present study was aimed to determine the change of platelet count and the associated risk of PTE. Methods: A retrospective 1:2 matched cohort study was performed to evaluate the risk of PTE in patient with gemcitabine-based chemotherapy for pancreatic cancer. Clinical parameter including rate of increment of platelet count (Inc-Plt) was checked in PTE group and non-PTE group. Inc-Plt was defined as the difference of platelet count from new cycle day 1 to last cycle day 15. The rate of Inc-Plt was defined as the rate of increased platelet count at new cycle day 1 compared with previous cycle day 15. Each patient in PTE group was matched with two patients in the non-PTE group. Inc-Plt = Platelet count at new cycle D1 ˗ Platelet count at last cycle D15 Rate of Inc ˗ Plt = Platelet count at new cycle D1 ˗ Platelet count at last cycle D15 Platelet count at last cycle D15 Results: From January 2010 to March 2015, 12 patients (9.1%) were diagnosed PTE during chemotherapy (PTE group) among 132 patients who received gemcitabine-based chemotherapy and 24 patients who did not have PTE were matched in non-PTE group. Age, sex proportion, body mass index, presence of metastasis, gemcitabine amount, previous anti-platelet agent medication, Karnofsky performance scale were not different significantly between two groups. The average Inc-Plt was 123,649±109,864/µl in PTE group and 141,978±129,846/µl in non-PTE group (p=0.42). The average rate of Inc-Plt was significantly higher in PTE group (32.1% in PTE group vs. 20.4% in non-PTE group, p=0.033). The average rate of Inc-Plt more than 30% was observed more frequently in PTE group (4.3±1.6 in PTE group vs. 2.1±1.8 in non-PTE group, p=0.039). Conclusion: The incidence of PTE was 9.1% during gemcitabine-based chemotherapy in pancreas cancer. The increment of platelet count and high level of platelet during chemotherapy are the risk of PTE.

Speaker
Biography:

Shabnam Ansari is a Scholar at the Department of Moalejat, Faculty of Medicine in Jamia Hamdard University, India.

Abstract:

Background: At present, liver transplantation remains the only curative option for the patients with cirrhosis and end-stage liver diseases. The survival rate and recurrent diseases remains the major issue in the patient post-transplantation. Unani medicine is one of the oldest traditional system of medicine, has been treating chronic liver diseases and cirrhosis since centuries. The purpose of our study was to assess the impact of Unani treatment in decompensated cirrhosis and collect data to warrant further clinical trials. Material & Methods: We conducted a case series with nine patients of cirrhosis and portal hypertension. Cases were confirmed by fibroscan and ultrasound and treated with Unani treatment orally for 3 to 7 months. Results were evaluated based on fibroscan, liver function test, EQ5D, CLDQ (chronic liver disease questionnaire), child pugh and MELD-Na Score. Results: Significant improvement in liver fibrosis and quality of life were achieved in the patients. Discussion: We reviewed the literature related to the herbal constituents of chief medicines used for the treatment in this case. The herbs have been proved for its potential anti-oxidative, anti-inflammatory, hepatoprotective, immuno-modulator and antiviral activities, suggesting plausible mechanisms of action in these cases. Conclusion: The preliminary findings indicate the potential therapeutic role of Unani treatment in decompensated cirrhosis. Clinical trials should be conducted to explore the further therapeutic potential of Unani treatment in decompensated cirrhosis.

Speaker
Biography:

Abstract:

Background: The genetic basis underlying liver fibrosis remains largely unknown. Quantitative sirius red staining and expression of alpha-smooth muscle actin (α-SMA) are accurate and reliable markers for liver fibrosis and fibrogenesis, respectively. Aims: To identify genetic alleles and underlying pathways associated with hepatic fibrogenesis and fibrosis at the genome-wide level. Methods: We conducted a genome-wide association study (GWAS) by examining the associations between 533,687 single-nucleotide polymorphisms (SNP) and the measurements of hepatic fibrogenesis (α-SMA staining) and fibrosis (Sirius red staining) in human liver samples collected from donors without heavy alcohol consumption or viral hepatitis (n=123). Following the GWAS, an expression quantitative trait loci (eQTLs) analysis was conducted to examine the relationship between candidate SNPs (p<10-4) and gene expression levels in the same sample set of liver tissues, by focusing on the genes in the region of ±1Mbp of each candidate SNP locus. The significant (p<0.05) eQTL-controlling genes were then examined in an enrichment analysis to identify molecular pathways using Ingenuity Pathway Analysis package. Results: At the p<10-4 level, we identified 71 and 73 candidate loci potentially affecting the fibrosis and fibrogenesis, respectively. Among which, 52 candidate loci for fibrosis and 58 loci for fibrogenesis were significant eQTLs of their nearby genes. Pathway analyses of these genes indicated that Macrophage Migration Inhibitory Factor (MIF)-mediated Glucocorticoid Regulation (p=0.003), MIF Regulation of Innate Immunity (p=0.005), and Endothelin-1 Signaling (p=0.009) were the top three pathways involved in the collagen accumulation, while Eumelanin Biosynthesis (p= 7.2 x 10-5), Glutathione Redox Reactions (p=0.001), and VEGF Signaling (p=0.002) for stellate cell activation. Interestingly, the MIF-mediated Glucocorticoid Regulation (p=0.004) and MIF Regulation of Innate Immunity pathways were also significantly associated with α-SMA expression (p=0.006). Conclusion: Our study identified candidate alleles and pathways strongly associated with hepatic fibrogenesis and fibrosis. The MIF signaling pathway may play a critical role in liver fibrosis.

Speaker
Biography:

Li Wenbin has completed his PhD from Sun Yatsen University and Post-doctoral studies from Sun Yatsen University School of Medicines. He is the Deputy Director of biliopancreatic Surgery, Sun Yatsen Memorial Hospital. He has published more than 25 papers in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

Associating liver partition with portal vein ligation (PVL) for staged hepatectomy (ALPPS) is rapidly develop and dissemination with the availability of many variants. But as far as we know, it is debatable whether the stage two of ALLPPS can be conducted or not in patients with HBV-associated liver cirrhosis. The regenerative capacity of future liver remnant (FLR) is the most important part of the stage two operation. 30 cases of ALLPPS with HBV-associated liver cirrhosis were completed in our center form Jan 2014 to Dec 2015. 21 cases were conducted stage two operation. We are trying to analyze postoperative liver pathology to evaluate the regenerative capacity of liver with the purpose to predict whether the stage two of ALLPPS can be conducted or not. Current data trend towards that Ishak modification ≤4 suggest the regenerative capacity of FLR is enough, but the final conclusion needs further research.