2^nd International Conference on Hepatology May 09-11, 2016 Chicago, Illinois, USA

Biography:

Wafa Amer is a Physician, awarded MBBCh in 2010 from Misurata University, Libya. She has migrated to Germany to learn state-of-the-art techniques and did her Master thesis at the Institute for Pathology at the University Hospital of Cologne, Germany.

Abstract:

Hepatocellular carcinoma (HCC) is the third most lethal cancer due to its late detection, high recurrence and limited therapeutic option. Since mitochondrial (mt) genome is highly susceptible to DNA alterations due to the lack of protective histones and limited repair system, the mt-mutation pattern can be targeted as a novel tool of tumor evolution analysis. Herein, we aimed to characterize intratumor clonal structure by ultra-deep sequencing of entire mt-genome for better understanding how HCC originate, develop and progress. In total, 48 HCC nodules and corresponding peri-tumor areas were analyzed. Primer sets spanning the whole mt-DNA were designed and multiplex-PCR setup was established. Target enriched libraries of mt-DNA was sequenced by MiSeq-platform and NGS data was interpreted by the CLC Software. Notably, 100% of reads mapped to the mt-target regions indicating efficient mt-primer design and a good run performance. Whole mt-genome screening revealed a wide spectrum of mt-alterations, typically distributed in the D-Loop region and the respiratory chain complex genes. Particularly in HCC nodules of non-cirrhotic origin mt-mutations were higher than cirrhosis-related HCC. However, high mt-mutation rate was also observed in the peri-tumor areas suggesting that mt-genome is susceptible at earliest stage of hepatocarcinogenesis. Furthermore, most HCC nodules of individual sample have identical mt-mutations indicating the monoclonal HCC origin. Interestingly, the increasing numbers and frequency of particular panel of mt-hot-spot mutations refer to the progression of HCC dedifferentiation. In conclusion, our mt-genome screening based approach representing rapid and sensitive molecular tool and provide novel insights in cancer diagnostics and therapeutic strategies.

Biography:

Zhiyu Xiao has completed his PhD from Sun Yat-sen University School of Medicine in 2011. He is now an Associate Professor of Sun Yat-sen Memorial Hospital. He has been engaged in the clinical and basic research of hepatocellular carcinoma for many years. He published several papers in reputed journals.

Abstract:

Drug resistance is a major factor contributing to the extremely poor prognosis of patients suffering from advanced-staged hepatocellular carcinoma (HCC). 5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent against HCC. Here, we found that protein tyrosine phosphatase, non-receptor type 13 (PTPN13, also known as FAP-1) was expressed at high levels in HCC patients who developed recurrence after chemotherapy and that changes in PTPN13 expression before and after chemotherapy were inversely correlated with recurrence time. In parental cells, after treatment with 5-FU, upregulation of total and surface Fas, downregulation of PTPN13 and activation of apoptosis were observed, while in 5-FU resistant cells, upregulation of PTPN13 resulted in resistance to apoptosis. After stable knockdown of PTPN13 in 5-FU resistant cells, improved chemotherapeutic efficiency was detected both in vitro and in vivo. More importantly, we provide evidence that miR-200c is upstream of PTPN13 using bioinformatics methods confirmed by luciferase reporter assays. We also demonstrate that miR-200c sensitizes 5-FU resistant cells to apoptosis. Moreover, resistance to 5-FU-induced apoptosis was effectively overcome by the addition of the apoptosis activator procaspase-activating compound 1 (PAC-1). 5-FU and PAC-1 synergistically inhibited HCC cell proliferation measured using in vitro, ex vivo and in vivo models. In conclusion, the upregulation of PTPN13 is one of the mechanisms that mediate 5-FU resistance in HCC. Combining 5-FU with the apoptotic pathway activator PAC-1 can overcome this resistance, suggesting that this combination may be a novel approach for the treatment of chemoresistant HCC.

Biography:

Zhong Li has completed his PhD from Shanghai Medical University and Postdoctoral studies from Shanghai Institute of Biochemistry, University of Rochester and Connecticut Health Center. He is the Vice President of Shanghai Institute of Cell Therapy, an immunotherapy researdch organization. He has published more than 31 papers in reputed journals and has been serving as a member of Precision Medicine Association affilated to China Medicinal Biotech Association.

Abstract:

Merlin (moesin-ezrin-radixin-like protein), encoded by the neurofibromatosis type 2 (Nf2) tumor suppressor gene, is a member of the band 4.1 family. As one of the most versatile tumor suppressors, it is capable of integrating several different mechanisms that regulate cell proliferation, motility, survival and signaling pathways. As we know, Merlin has at least five splicing forms. However, little is known about the functional importance of these splicing forms. To understand the roles of Merlin in the process of tumorigenesis and tumor metastasis, we studied Merlin and its splicing forms in hepatocellular carcinoma (HCC). Our data shows that Merlin is present at low levels in HCC specimen, particularly in metastatic tumors, where it is associated with a poor prognosis. Surprisingly, a splicing variant of Merlin that lacks exons 2, 3 and 4 (2–4Merlin) is amplified in HCC and portal vein tumor thrombus (PVTT) specimens and in the CSQT2 cell line derived from PVTT. Our studies show that 2–4Merlin interferes with the capacity of wild-type Merlin to bind b-catenin and ERM, and it localizes in the cytoplasm rather than at the cell surface. Furthermore, 2–4Merlin overexpression increases the expression levels of b-catenin and stemness-related genes , induces the epithelium–mesenchymal-transition phenotype promoting cell migration in vitro and the formation of lung metastasis in vivo. Our results indicate that the 2–4Merlin variant disrupts the normal function of Merlin and promotes tumour metastasis.

Biography:

Mohammed Omar Khalifa has completed his MD from Ain Shams University, Cairo, Egypt. He is an Assistant Professor of Tropical Medicine Department. He has published many papers in reputed journals.

Abstract:

Background & Aim: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Egypt has the highest prevalence of HCV in the world and the prevalence of HCC is increasing in the last years. The aim was to study epidemiological characteristics of HCC in Egypt. Methods: Retrospective chart review of 1456 Egyptian patients with HCC was done. Records of 1313 patients (1035 males, 278 females; median age 56 years) fulfilling diagnostic criteria for HCC, were analyzed for clinical, etiological, radiological and tumor characteristics. Results: The majority of cases (75%) were from rural areas. The most frequent age category affected by HCC was between 51 and 60 years (45.7%); 50% of the patients reported accidental discovery of their hepatic focal lesions. The major presenting symptom was newly developed right hypochondrial pain (66.3%). HCV Ab was detected in 91.32% of the studied patients while HBV infection was reported in 2.51%. 59.3% of patients had AFP levels below 200ng/ml. On studying tumor characteristics, the right lobe of the liver was more frequently occupied by the focal lesions (75.4%) than the left lobe (15.7%) and 12.5% of patients had bilobar affection. Five hundred and six patients (38.6%) had more than one hepatic focal lesion and 228 patients (17.4%) had tumors occupying >50% of the liver. Conclusion: HCC is a major health problem in Egypt and its incidence is increasing. The high prevalence of HCV infection makes screening programs and surveillance of those patients a very important tool to early detect cases of small HCCs.

Biography:

Mahmoud M Zakaria Ibrahim has worked in the Department of Laboratories (Microbiology, Clinical Chemistry and Clinical Hematology Labs.) of Urology & Nephrology Center, Mansoura University. He is currently working as a Molecular Biologist in Research Building (Gene Expression, Tissue Culture, Stem Cell Labs). He has obtained his Master’s degree in Immunology and PhD degree in Human Physiology (2012). He has publicized 11 manuscripts in reputed journals in the field of cancer research and stem cell differentiation. He is currently a Supervisor of Gene Expression Lab.

Abstract:

Objective: The present study aimed to investigate the in vitro anticancer effect of Aloe vera and Calligonum comosum extracts against hepatocellular carcinoma (HepG2) cells. Methods: HepG2 cells were tested against different doses of A. vera and C. comosum. Viability of the cells was assessed by MTT assay. Evaluation of apoptosis and DNA damage in HepG2 cells were performed using Annexin V Apoptosis Detection Kit. The expression of p53 and anti-apoptotic (Bcl-2) were tested by Real Time-PCR and flow cytometer analyzer. Hematoxylin & Eosin stained sections from untreated and treated HepG2 cells were observed using light microscopy. Results: The IC50 values of A. vera and C. comosum extracts were (10.45±0.31) and (9.6±0.01) µg/ml respectively. The extracts separately increased cytotoxicity against HepG2 cells in a time and dose dependent manners. Also, it apparently induced apoptosis through increase P53 and decrease Bcl-2 genes expressions. Conclusion: The results indicated that the extracts could have anti-hepatocarcinogenic effect at least in part through modulation of apoptosis.

Biography:

Kai-Fu Tang has completed his MD in 1995 from Chongqing Medical University and PhD from Chongqig University. He is the Director of the Digestive Cancer Center of Wenzhou Medical University. He has published more than 30 papers and has been serving as an Editorial Board Member for several journals.

Abstract:

Hepatitis B virus (HBV) infection is one of the major causes of hepatocellular carcinoma (HCC), but the molecular mechanisms underlying HBV-related HCC are still incompletely understood. Knockout of Dicer in hepatocytes led to spontaneouse HCCs , we found that Dicer is downregulated in the liver tissues of chronic hepatitis B patients and HCC tissues. Therefore, we proposed that decreased Dicer expression is critical for the development of HCC. Here, I will address the molecular mechanism underlying why Dicer downregulation lead to the development of HCC. Firstly, Dicer is essential for the maintenance of genome stability, decreased Dicer expression causes DNA damage, which may induce gene mutation and lead to carcinogenesis. Secondly, Dicer interacts with SIRT7 and holds a proportion of SIRT7 in the cytoplasm, decreased Dicer expression leads to H3K18 hypoacetylation upon DNA damaging. H3K18 deacetylation is critical to the maintenance of oncogenic transformation. Therefore, Dicer may participate in carcinogenesis via regulating H3K18 deacetylation. Thirdly, Dicer processes 7SL RNA into small fragments, which function as dominant-negative regulators of the full-length 7SL RNA, and interfere with signal recognition particle (SRP) complex formation. Decreased Dicer expression enhances SRP-mediated protein targeting, and increases hepatitis B surface antigen (HBsAg) secretion. HBsAg repress MICA and MICB expression via induction of cellular miRNAs in HCC cells. Therefore, Dicer may participate in antitumor immune response. Fourthly, Dicer may regulate tumor development via different miRNAs.

Biography:

Bingshui Xiu has completed his PhD from Beijing Institute of Basic Medical Sciences. She has published more than 14 papers in SCI journals

Abstract:

There are about 150 thousands of HCV infection individuals in China, which is a major public health problem of China. The correct detection of HCV is foundation for blood screen, clinical diagnosis and antiviral treatment. In this report, we summarize the main procedure and tests used in HCV detection in China. According to Blood Donation Law of China established in 1998, anti-HCV screen is enforceable, which dramatically decrease the HCV transmission by blood. In 2015, NAT were forcibly used in blood screen all over China, the procedure to HCV screen changed accordingly, but its effect needs to be evaluated further. In HCV diagnosis, anti-HCV assay is common in preliminary diagnosis. NAT, especially real-time reverse transcriptase polymerase chain reaction, are commonly used to monitor the virological responses during the antiviral treatment in China. According to Hepatitis C Prevention Guidelines announced in 2015, HCV genotype assay has important clinical implication as a marker of responsiveness to IFN. But HCV serotype tests for 1b and 2a are gaining more attention for their convenience. Recently, direct-acting antivirals (DAAs) to HCV (daclatasvir, ombitasvir and ledipasvir) were used. HCV mutation assay and new biomarkers for DAA treatment and prognosis of HCV infection are urgently needed.

Biography:

Arnolfo Petruzziello is the Head of the Diagnostic Virology and Molecular Biology Unit of National Cancer Research IRCCS Italia Fondazione G. Pascale in Naples. He has done Post-graduation in Microbiology and Virology and PhD in Molecular and Cellular Pathology. He is an Editorial Board Member and peer-reviewer for: World Journal of Gastroenterology and Archives of Microbiology and Biotechnology.

Abstract:

Background: Hepatocellular carcinoma (HCC) is the third most common cause for cancer death in the world, especially in patients with chronic hepatitis C virus (HCV) infection. The rate of progression from chronic hepatitis to HCC is variable and several factors have been identified as important predictors of progression, some related to the host (older age, longer duration of infection, male sex or alcohol consumption >50 g/day), others to the environment (Hepatitis B virus or HCV infection). Despite several studies suggesting an association between HCV genotype 1b and risk of HCC, no consenus has emerged yet on this matter, which is still controversial. The purpose of this study was to clarify whether the genotype 1b is associated with a higher risk of HCC than other genotypes. Material & Methods: A total of 121 consecutive cases of HCC, fulfilling the diagnostic criteria from the Barcelona 2000 EASL conference, and 125 patients with other malignant tumors as control, enrolled between February 2013 and November 2015, were included in the study. Serum of each HCC or control patient was evaluated for serological evidence of HCV infection (Vitros Ortho Clinical Diagnostics), viral load estimation by Taqman Real time PCR system (Roche Diagnostic) and genotyping by HCV LiPA test (Siemens) . Results: About eighty per cent (80.8%) of HCC patients had positive anti-HCV which was significantly greater than the control group (34.4%, p=0.01). Anti-HCV positive patients have a risk of progression to HCC almost 8 times than the control group (OR= 8.04). The male/female ratio for the HCC cases was 3.06:1. Males with HCC significantly showed to have about 4 times risk of exposure to HCV infection (OR=3.9). Majority of HCC patients were >70 years (71.0% vs. 58.0% in the control group) and over eighty per cent of them had underlying cirrhosis at presentation (84.0%). HCV RNA seropositive rate was significantly higher (71.2%) among HCC patients if compared to the control group (44.2%, p=0.01). No difference in levels of viral load was found between HCC patients and the control group. The most prevalent genotype in HCC patients was 1b (59.4% vs. 26.4% in the control group, p=0.05), whereas the most predominant genotype in the control group was 2a/2c (63.2% vs. 21.7% in HCC patients, p=0.01). Moreover, the genotype 3a, completely absent in the control group, is the third most common genotype in the HCC patients (5.9%). Conclusion: HCV genotype 1b is associated with a statistically higher risk of developing HCC compared to other genotypes. Patients with cirrhosis that are infected with this genotype require more intensive surveillance for the early detection and aggressive management of neoplasia

Biography:

Ishank Goel is a 2nd year resident at the DMIMS University, Sawangi (Meghe), Wardha, Maharashtra, India. He has presented oral presentations and poster at NAPCON-2014 and 2015, CME Colors Hospital, Nagpur, India and various other conferences in India. He has attended and served in many social health camps. He also has done a case prensentation in a national level conference. He is a certified NALS and PALS provider.

Abstract:

This cross sectional observational study was done in the paediatric wards and ICU of Acharya Vinoba Bhave Rural Hospital, Sawangi, Wardha, Maharashtra, Central India. In our study, children below 16 years with serology positive dengue fever were included. The dengue score formulated in our institute which was pre-designed and pre-validated was used to grade these children according to symptomatology. A score of >20 out of 30 indicated a poor prognosis, 11-19 indicated good prognosis (with some morbidities) and a score of 0-10 indicated excellent prognosis. Outcome was measured in terms of death, ventilatory support, encephalitis, need for transfusion of blood products, shock, prolonged mean duration of stay. In our study, out of the 120 tested patients, 50 children with dengue serology positive were further graded according to their presenting symptoms like tachypnea (4), urine output (4), deranged LFTs (4), hypotension (4), pulse pressure (3), convulsions (3), capillary leak (2), platelet count (2), heart rate (2), fever (1) and rash (1). We found that 42 out of the 50 (84%) had hepatic involvement in the form of deranged LFTs or organomegaly and the remaining 8 had no hepatic involvement. Out of the 42, liver involvement was seen as follows: raised alanine transaminase (ALT) (80.9%), raised aspartate aminotransferase (AST) (71.4%), hepatomegaly (66.7%), reduced serum albumin (59.5%), raised alkaline phosphatase (42.8%) and prolonged prothrombin time (PT) (30.9%). We found that hepatic involvement had a statistically significant association with poor outcome in patients of dengue (along with other markers like tachypnea, urine output and hypotension).

Biography:

Krutika A Kurhade is a 2nd year resident in the Department of Paediatrics in DMIMS, Sawangi, Meghe. She worked as a Clinical Observer in Paediatrics in Eric Williams Medical Sciences Complex Trinidad & Tobago, UWI and in Lad Child Care Hospital, Nagpur, Mahrashtra, India. She also worked as a House Officer in the MICU of IGGMC, Nagpur, India. She has attented various social health camps in the Vidarbha region, presented a paper and case presentation in two national level conferences. She has also attended many other national level CMEs and conferences on topics of nutrition, neurology and genetics.

Abstract:

In this prospective observational study, the value of first day bilirubin in predicting development of significant hyperbilirubinemia in healthy term neonates was evaluated in the maternal and neonatal wards of AVBR hospital, Sawangi, Wardha. The study included 388 full term healthy neonates out of 6082 deliveries in study period. Newborns with Rh incompatibility, prematurity etc. were excluded. Transcutaneous bilirubin (TCB) was measured on 12, 24, 48 and 72 hours of life. To assess the correlation between TCB and serum bilirubin, blood was sent to the biochemistry laboratory for measuring serum bilirubin levels (at 72 hours of life) by modified Van den Bergh's test. There were 193 cases of neonatal hyperbilirubinemia out of 388 cases (49.74%). We determined a cut off value of 5 mg/dl for the prediction of neonatal hyperbilirubinemia at 24 hours of life (NPV=77). The mean value of bilirubin at 12, 24, 48 and 72 hours was found as 3.69, 5.17, 9.05 and 13.18 respectively. Neonatal hyperbilirubinemia was found to be more on 24 and 72 hours (49.74%) as compared to 12 hours (35.2%) and 48 hours (44.32%). Average values of bilirubin in newborns developing hyperbilirubinemia at 12, 24, 48 and 72 hours were 5.02, 6.88, 12.15 and 16.95 respectively. A TCB measurement of 5 mg/dl in first 24 hours of life predicted nearly all the term newborns had hyperbilirubinemia (≥13) mg/dl at 72 hours of life. A TCB measurement of 4 mg/dl at 12 hours predicted 35.56% of the cases who developed hyperbilirubinemia at 72 hours of life. Correlation of TCB and serum bilirubin was found to be significant (correlation coefficient (r) 0.9379). First day TCB level can predict development of subsequent hyperbilirubinemia.

Biography:

Yuling Sun has completed his PhD from Zhejiang University School of Medicine. He is the Director of the department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University. He has published more than 12 papers in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

Increasing evidence has indicated that there were distinct variations in Budd–Chiari syndrome (BCS) prevalence, its etiological distributions, clinical characteristics, and sites of occlusion, and the selected treatment modalities for BCS patients between China and the western countries. The clinical manifestation of BCS is heterogeneous. The triad of abdominal pain, hepatomegaly and ascites is commonly present in patients. The blood failure of draining from the liver leads to congestion resulting in portal hypertension or inferior venacaval (IVC) hypertension, inducing various changes of physiological functions. Through the "gut-liver axis", the liver function is closely linked to gut microbiota; however little is known about the gut microbiota profile in patients with Budd-Chiari syndrome.88 patients (31 HC, 20 LC, 31 BCS) who were matched with their age, gender and BMI carried out in accordance with the criteria of gut microbiota. We first established the framework of gut microbial communities in Chinese patients with Budd-Chiari syndrome. Unusually abundant rare species of bacteria were found in the BCS patients. At the phylum level, Tenericutes were significantly decreased when compared with the liver cirrhosis and health control group. The high abundance of Megamonas sequences was a feature of BCS group, could be used as a microbial signature for the differential diagnosis. Our research represents an important step for Original basic between Budd-Chiari syndrome and gut microbiota.

Biography:

Rosa M Pascale is currently working as an eminent Faculty member at Department of Biomedical Sciences, University of Sassari in Italy. She has published numerous research papers and articles in reputed journals and has various other achievements in the related studies. She has extended her valuable service towards the scientific community with her extensive research work.

Abstract:

Background & Aim: Recent observations suggests, contribution of Yes-associated protein (YAP) upregulation to hepatocellular carcinoma progression (HCC). We analyzed the connection of YAP deregulation with genetic susceptibility to hepatocarcinogenesis and HCC stemness and aggressivity. Methods: HCC from F344 and BN rats are genetically susceptible and resistant to hepatocarcinogenesis, respectively; human HCC from patients with poorer prognosis (<3 years survival, after partial liver resection, HCCP) or with better outcome (>3 years survival; HCCB) were used. Gene expression was evaluated by qPCR and immunoblotting, and functional experiments were done using HepG2, Huh7, and Hep3B liver cell lines. Results: Higher upregulation of Yap and of its target CTGF was seen in F344 rat HCC than in BN HCC which was associated with highest increase in Yap-tyr357, p73 phosphorylation, and Caspase 3 cleavage in HCC from resistant BN rats. Upregulation of YAP, CTGF, 14-3-3 and YAP-14-3-3 complex, TEAD and YAP-TEAD complex reached highest values in human HCCP. In contrast, YAP-ser127 decreased with lowest values in HCCP, and YAP-tyr357, p73 phosphorylation and Caspase 3 cleavage showed highest increase in human HCCB. Stem cell markers NANOG, OCT3-4, and CD133 upregulation progressively increased from human HCCB to human HCCP and was significantly correlated to YAP and YAP-TEAD expression. Growth rate was 2.5-3 times lower, between 48 and 96 hours, in HepG2 than in Huh7 and Hep3B cells. These modifications were associated with lower YAP and NANOG, OCT3-4, and CD133 expression in HepG2 than in Huh7 and Hep3B cells at 48 hours. YAP downregulation by specific siRNA in Huh7 and HepG3 cells led to significant decrease in NANOG, OCT3-4, and CD133 expression. In contrast, sharp upregulation of stem cell markers was induced in HepG2 cells by forced YAP overexpression. Conclusions: Our results indicate: YAP signalling deregulation in HCC is under genetic control; Genetic resistance to HCC is associated with highest phosphorylation of Yap at tyr357 and p73, and highest apoptosis; YAP changes favoring YAP-14-3-3 and YAP-TEAD complexes formation, associated with cell survival, contribute to HCC aggressivity. In contrast, YAP changes favoring apoptosis, such as YAP phosphorylation at tyr357, are associated with better HCC prognosis and; YAP upregulation favors HCC stemness and aggressivity.

Biography:

Amedeo Columbano has completed his PhD from Cagliari University and Post-doctoral studies from the Department of Pathology (Toronto, Canada). He is the Director of the PhD program in Molecular and Translational Medicine at Cagliari University. He has published more than 100 papers in reputed journals and has been serving as a referee for the most important Hepatology journals.

Abstract:

Warburg metabolism is associated with cancer, but remains unclear whether it characterizes early phases of tumorigenesis. Here, we performed a metabolic characterization by assessing expression level, activity and modulation of several enzymes with key roles in glycolysis, pentose phosphate pathway (PPP) and oxidative phosphorylation. Preneoplastic hepatic lesions and hepatocellular carcinomas (HCC) were induced in rats by a single dose of diethylnitrosamine (DENA) followed by 2-acetylaminoaminofluorene (2-AAF) and partial hepatectomy. Expression of metabolic genes was also analysed in macrodissected preneoplastic nodules and HCC cells obtained by perfusion of HCC-bearing rats and in two different cohorts of human patients carrying HCC. A switch from OXPHOS to PPP was observed in very early preneoplastic lesions generated 10 weeks after DENA treatment. This metabolic reprogramming was observed only in the most aggressive preneoplastic lesions positive for CK-19. PPP induction shown by increased glucose 6-phosphate dehydrogenase (G6PD) was associated with inhibition of succinate dehydrogenase by the chaperone TRAP1 and increased expression and activity of citrate synthase. Activation of the NRF2/KEAP1 pathway and down-regulation of miR-1 accompanied the metabolic reprogramming in CK-19+ preneoplastic lesions. Accordingly, NRF2 silencing decreases G6PD and increases miR1 expression, consequently inhibiting PPP, while forced expression of miR1 downregulated G6PD expression in HCC cells. Finally, an inverse correlation between miR1 and its target gene G6PD was found in human HCCs. The results demonstrate that metabolic reprogramming takes place at early stages of hepatocarcinogenesis and is likely the consequence of the concomitant activation/increase of the NRF2-KEAP1 pathway and TRAP1.

Biography:

Nikhat Ahmed has completed her PhD from University of Surrey, UK and Post-doctoral studies from Tufts University, School of Medicine. She was the chair and Dean of Science at University Of Karachi and presently, she is the Dean of Research, at Ziauddin University, Karachi, Pakistan a premier organization. She is representing Pakistan, as Council member of AOHUPO (Asian Ocenia Human Proteome Organization), and has published more than 65 papers in reputed journals and has been serving as Editor and Editorial Board Member of journal of repute.

Abstract:

Proteomics-based clinical studies have been shown to be promising strategies for the discovery of novel biomarkers of a particular disease. To gain insight into development of Hepatocellular carcinoma utilizing promising strategies (2 dimensional electrophoresis and ESI-QTOF-MS/MS) we aimed to identify potential biomarkers for hepatocellular carcinoma (HCC) and analyzed a set of 115 samples (HCC=50, Fibrosis= 50 & Control= 15). From the series of seventeen differentially expressed proteins, collectively we identify annexin A4 (ANXA4) an intracellular Ca2+ sensor, as a new biomarker for early diagnostic and prognostic potential. Expression of ANXA4 was found to be up- regulated (fold change ≥ + 2.0, P ≤ 0.05) in HCC as compared to fibrosis and control. After validated current finding, we applied in silico analysis to integrate the data generated from proteomics technologies. We extend this current understanding to demonstrate the significantly induced phosphorylation and S-nitrosylation signals by insilico study, suggesting a role of ANXA4 in cell survival may have implications for cancer progression and chemoresistance. Moreover, we revealed interacting partner of ANXA4 bestowed with critical capabilities, namely apoptosis, cell cycling, anticoagulation, cell motility and stress resistance that together demonstrate their possible role in cancer progression. Overall, our results shed new light on the potential of biomarker ANXA4 as biomarker used for early diagnosis, prognosis prediction, and personalized treatment of HCC.

Biography:

Zhaohui Tang is the Director of general surgery department in Xinhua Hospital affiliated to Shanghai JiaoTong University School of Medicine. He is good at diagnosis and treatment of hepatobiliary diseases, especially in the field of intrahepatic cholangiocarcinoma. There are differences related to the prognosis after surgery of ICC patients due to the enormous heterogeneities of ICC. Multiple cellular origins may play a key role in the development of ICC, so he proposed that view cellular origin from perspective of tumor heterogeneity, which may contribute to the improvement of ICC current classification methods, providing guidance for treatment.

Abstract:

Intrahepatic cholangiocarcinoma (ICC) is an extraordinarily heterogeneous malignant disease among the tumors that have so far been identified. The cancer cell-of-origin has important implications for tumor cell fate and cancer phenotype. Recent data suggest that multiple cellular origins of ICC including differentiated hepatocytes, intrahepatic biliary epithelial cells (IBECs)/cholangiocytes, pluripotent stem cells such as hepatic stem/progenitor cells (HPCs), biliary tree stem/progenitor cells (BTSCs), and within peribiliary glands (PBGs). Both somatic mutagenesis and epigenomic features are highly cell-type-specific, that is, multiple cellular origins may profoundly influence genomic landscapes, key signaling pathways, driving phenotypic variation and pose significant challenges to personalized medicine, drug response and patient outcome. Specifically, the cellular origin of ICC can be accurately determined based on the distribution of mutations along its genome through Roadmap Epigenomics Program. Understanding ICC heterogeneity of cellular origins and molecular mechanism may contribute to establish hierarchical model of carcinogenesis and improve anatomical-based classification. The advent of personalized medicine for ICC treatment may enable the actual origin of the cellular and molecular mechanism of ICC to be determined to improve diagnosis, therapies and prognosis.

Biography:

Abdul Malik has completed his PhD in 2007 from JamiaMilliaIslamia, New Delhi and Post doctoral studies at Department of Medicine, Maulana Azad Medical College, New Delhi. Currently, he is working as an Assistant Professor, College of Applied Medical Science, King Saud University, Saudi Arabia, since January 2011. He has published papers in reputed journals in the field of virology and has also presented them in International Conferences.

Abstract:

Background & Aim: Mutant Hepatitis B with precore stop codon has been reported to be associated with severe liver damage in HBeAg negative patients with hepatocellular carcinoma. Clinically, the biological importance of pre-core G1896A mutation is not well established. The purpose of the present study was to determine hepatitis B virus genotypes and also to elucidate the association of G1896A mutation of precore gene and the severity of liver damage in HBV related HCC cases. Methods: Detection of HBV DNA sequences was carried out by polymerase chain reaction (PCR) using primers derived from the precore region of HBV genome. Ligase Chain Reaction (LCR) assay was performed to screen the presence or absence of G1896A mutation. Direct nucleotide sequencing was done to confirm the results of LCR. A total of 116 HBV related cases who attended the medical Out Patients Department and wards of LokNayak Hospital, New Delhi, India were screened over the period of 3 years. Patients having super-infection with HDV/HCV/HIV and past history of interferon therapy were excluded. Results: Sequence analysis of viral DNA established that the G1896A mutation was observed in 32 cases in HCC cases. Phylogenetic analysis revealed 60% isolates belonged to genotype A, while 20% belonged to genotype Dand 20% belonged to genotype E. Conclusion: The present data suggests that precore G1896A mutations is responsible for 27.2% of the patients of Asian Indian origin suffering from HBV related HCC cases and these cases are more symptomatic and aggressive in patients with the mutant form of the virus as compared with the wild form.

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.

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.

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.

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.

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.

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.

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.

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.

Biography:

Wenbin Li 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:

Chemokine ligand 18 (CCL18) has been associated with hepatocellular carcinoma (HCC) metastasis. Here, we demonstrated a novel mechanism through which CCL18 en-hances cell migration, invasion, and epithelial–mesenchymal transition (EMT) in HCC. (1) Using immunohistochemistry, we analyzed the expression of PITPNM3, a molecule that correlated with CCL18 signaling, in 149 HCC tissue specimens. The results showed that PITPNM3 expression is highly associated with tumor metastasis and differentiation; (2)in vitro experiments showed that CCL18 enhances cell migration, invasion, and EMT in PITPNM3 (+) HCC cells but not in PITPNM3(-) cells. Silencing of PITPNM3 by short interfering RNA (siRNA) inhibited the induction of cell migration, invasion, and EMT by CCL18; (3) Cell migration, invasion, and EMT induced by CCL18 accompanied with the phosphorylation of IKK and IKBα as well as p65 nuclear translocation in PITPNM3(+) HCC cells, but not in the cells that PITPNM3 is silenced with siRNA, implying that the activation of NF-κB signaling is involved i n t he action of CCL18/PITPNM3.These results suggest that CCL18 enhances HCC cell migration, invasion, and EMT through the expression of PITPNM3 and the activation of the NF-κB signaling pathway.

Biography:

Eve-Isabelle Pecheur has completed her PhD in 1997 from University Paris XI and Post-doctoral studies from Groningen University of Medical Sciences (Netherlands). She leads her research group at the Cancer Research Center of Lyon. 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:

Background & Aims: The hepatocyte microenvironment at the vicinity of cell surface (a.k.a. glycocalyx) is rich in membrane-anchored proteoglycans which are receptors for extracellular matrix proteins, cytokines, growth factors, lipoproteins and infectious agents. The hepatitis C virus (HCV) infects hepatocytes, after its initial attachment to the heparan sulfate proteoglycan syndecan-1. Here we investigated the link between the hepatocyte microenvironment, HCV entry and infection. Methods: Studies were carried out by RNA silencing, immunoprecipitation, proximity ligation assays, immunofluorescence and confocal imaging, coupled to cross-correlation and statistical analyses. Results: Hepatocyte infection by cell culture-grown HCV or clinical isolates was inhibited after knockdown of syndecan-1 or xylosyltransferase-2, a key enzyme of proteoglycan biosynthesis. Simultaneous knockdown of syndecan-1 and CD81, a receptor of HCV entry, strongly inhibited infection, suggesting their concerted action. At early infection stages, syndecan-1 and virions colocalized at the plasma membrane, and were internalized along with CD81 in endosomes. Direct interactions between syndecan-1 and CD81 were revealed in primary and transformed hepatocytes by immunoprecipitation and proximity ligation assays. This underpins the relevance of this interaction to HCV internalization and infection. Expression of syndecan-1 and xylosyltransferase-2 was altered within days post-infection, and the remaining syndecan-1 pool colocalized poorly with CD81. Conclusions: Syndecan-1 plays an important role in HCV entry and infection, and may act in concert with CD81, as syndecan-1 is detected in complex with CD81. Infection modulates syndecan-1 and xylosyltransferase-2 expression, underscoring a profound reshuffle of the hepatocyte glycocalyx early in infection, likely required for settling optimal conditions of viral propagation.

Biography:

Raffaella Romeo graduated from Medical School University of Milan in 1989. She is a specialist in Liver Disease since 1992, and completed her PhD in 1998. She did her Postdoctoral studies at Pasteur Institute Paris (France). She is a Visiting Scientist at NIH, Bethesda (MD). Since 2005, she is a elected member of the expert committee for virology and vaccines of the United States Pharmacopeia, Rockville, MD. She has a National Academic Qualification as Associate Professor of Gastroenterology since 2013. She has extensively worked in the area of molecular biology of hepatitis B, C and delta viruses as well as hepatocellular carcinoma. She is the author of several publications on international journals. She is also a invited speaker at several International meetings.

Abstract:

Chronic HDV infection has lately regained clinical importance because of the evidence of increasing prevalence in Western countries. Even though a systematic population’s screening is still not performed, main areas of prevalence are the Mediterranean basin, the Middle-East, Central and Northern-Asia, West and Central-Africa, the Amazonian basin, Northern South-America and the Asia-Pacific region. It is estimated a global burden of about 20 million cases worldwide. Epidemiological studies on genotypes distribution have demonstrated that different clinical courses may rely upon the presence of more virulent genotypes. Progressive forms of infection are reported from Far-East and South-America, where genotypes 2 and 3, respectively, are endemic. Genotype 1 is present worldwide associated to disease with variable course. Genotype 4, typical in the Far East, is characterised by a mild hepatitis. Genotypes 5-8, described in West and Central Africa, are still poorly studied, in terms of clinical course. The different clinical course determined by genotypes may depend upon different virion assembly efficiency as well as RNA replication fitness. Cirrhosis occurs within few years from HDV infection in about two thirds of cases, and there is a three-fold higher risk of progression to cirrhosis as compared to patients with chronic HBV mono infection only. Treatment of chronic HDV infection is difficult. The ideal drug would be able of inducing HDV clearance but also HBV clearance. Several attempts have been made with various drugs (IFN, PegIFN, Ribavirin, Lamivudine, Adefovir, Tenofovir) alone or in combination, with disappointing results. Attempts on looking for new antiviral compounds are currently ongoing.

Biography:

André-Jean Remy, is Head of Hepatology and Gastroenterology Unit & of Social Medicine Unit of Perpignan Hospital. He is the Medical coordinator of Mobil Hepatitis Team, General Secretary of ANGH. He is an Administrator of AFEF (French Liver Diseases Association) and a specialist of viral hepatitis in drug users, inmates and precarious populations. He has published more than 150 scientific articles.

Abstract:

Introduction: Hepatitis C (HCV) rate is higher in the prisoners’ population than in the general’s one in France between 5 and 7% (INVS on 2004, PREVACAR). Prisoners accumulate risk factors before their confinement but the prison in itself represents a risk factor: Syringes or straw share, homemade tattoos, etc. Global incidence of HCV in France was 2700 and 4400 new cases per year. On the other hand HCV incidence in jailhouses was not known. Screening of HCV is systematically proposed in the entrance to detention in France but its renewal, recommended by the Methodological Guide of sanitary care is not still applied correctly. In this context, point of care testing (POCT) use could constitute an interesting alternative in classic serology and was recommended in French HCV experts report in 2014 and in national guidelines in 2015. Objective: Use HCV POCT in prison as a supplement to the classic serology to study the incidence of new HCV infections. Methods: HCV prevalence in our establishment is situated in national average around 7%. HCV serology realized by venous way was proposed to all incomers in Perpignan detention center. POCT was proposed to 3 types of prisoners: 1/refusal or impossibility of venous way 2/transfer of another penitentiary and previous negative serology 3/presence in detention 12 months old superior and previous negative serology. In case of positivity a FIBROSCAN and a complementary biological balance sheet are realized. Results: 333 HCV POCT was realized in 24 months: Group-1; 15 %, group-2; 27%, group-3; 58%. Two serologies were positive. The 2 inmates were imprisoned for more than 6 months and the viral load was positive. A patient had gone out in permission one week and a patient had never gone out of detention. The use of drugs was route of contamination in 2 cases. The calculated incidence was 3/1000 per year or potentially 470 new cases of HCV infection in France per year among the prison population (78246 prisoners on June 1st, 2015). Discussion/Conclusions: HCV POCT is useful in jailhouses because there are HCV high risk places. These routed of contamination could be more than 10% of HCV new cases. So it was also necessary to give harm reduction tools for all prisoners.

Biography:

Vince Fragomeli is a Clinical Nurse Consultant at Department of Gastroenterology and Hepatology in Nepean Hospital, Australia.

Abstract:

Hepatitis B and C are major global public health concerns with some 500 and 200 million worldwide cases respectively. Despite the availability of effective curative therapies for hepatitis C virus (HCV) and viral suppressive therapies for hepatitis B virus (HBV), to date only a minority of infected patients receive treatment throughout the world. In the general population, morbidity and mortality associated with chronic HCV and HBV infection is on the rise. Increased notifications of advanced liver disease and hepatocellular carcinoma are also rising at an alarming rate. This situation is more pronounced in the Opioid Substitution Therapy (OST) setting where people living with hepatitis B or C historically have been reluctant to access liver services. In Australia, an estimated 41% to 68% of people who inject drugs (PWID) are HCV-positive and between 28% and 59% of users are estimated to have been exposed to HBV. Although current treatment guidelines suggest that active drug use should not preclude people from HCV treatment, uptake of therapy thus far has been low to say the least. Patient, physician, social, and logistical-related barriers contribute to the low uptake of HCV/HBV treatment among PWID. Traditional means of managing HCV/HBV infection, that is, referral to a secondary or tertiary health centre, to date has proven to be an ineffective model for providing assessment and treatment options for this patient population. Approximately 50,000 Australians receive OST through a range of services, including public and private clinics, thus this setting is an ideal target for identifying and treating people at risk for and already infected with HBV and HCV. This is of particular relevance with the emergence of all-oral direct antiviral agents (DAA) that are more tolerable and efficacious than conventional interferon subcutaneous injection based treatment. This paper will describe the creation and functioning of a multidisciplinary, nurse-led model of care initiated by a teaching hospital in Sydney, Australia, that integrates viral hepatitis screening, assessment and treatment into the OST setting. In the world of escalating burden of liver disease and healthcare costs, this nursing model of care has been effective in enhancing access to HBV/HCV services among the marginalized injecting drug use population.

Biography:

Xueshan Xia has completed his PhD from Chinese Academy of Science and then successively was taken as visting scholar in National Institute of Infectious Disease of Japan and Mecine School of University of Utah. He is the Dean of the FACULTY of LIFE SCIENCE and Technology, Kunming University of Science and Technology, and the Director of Yunnan Provincial Center for Molecular Medicine. He has published more than 25 papers in reputed journals and has been serving as a reviewer of several journals.

Abstract:

Occasionally, a sharp increasing of HCV infection was found in People’s Hospital of Luxi county, Yunnan province of China. The most of these outpatinets are resided in Baima-Zhehei, a common village in Luxi. A total of 900 plasma samples were collected including 746 from adult and 154 from children less than 12 years old. ELISA for HCV antibody and RT-PCR were conducted to detect HCV infection. Of 746 adult participants, the HCV sero-positive rate is 41.95% (313/746) and HCV RNA positive rate is 32.04% (239/746). Comparatively, the sero-positive (0.65%, 1/154) and RNA positive (0.65%, 1/154) rates of children are significant lower than that of adults. According their informed risk behaviors, using of inadequately sterilized syringe is deduced as major risk factor for their HCV infection occurred at least 15 years ago. The fragment of NS5b gene were amplified and subsequently sequenced. Of randomly selected and successfully genotyped 71 samples, 3b was determined as the predominant HCV subtype (73.23%, 52/71), followed by 1b (15.49%, 11/71) and 2a (8.45%, 6/71). As the common HCV genotypes in China, 1b and 2a haven’t been detected as the predominant HCV genotype. Alternately, 3b, being identified frequently in neighbored Southeast Asian countries, was found as the most prevalent HCV genotype. Moreover, 2 cases of 6n, the common HCV genotype in SE Asia, were simultaneously revealed in this population. In MACC analysis using Beast software. these 3b strains were shown to have high relationship with 3b strains in SE Asian countries. Surprisingly, their original time was estimated as 1940s, it is far different with our suspected 1980s, the start time of opening and reforming policy in China. These findings enriched our understanding on HCV epidemic in Yunnan and is helpful for HCV prevention and controlling.

Biography:

Yuming Wang is currently the Academic Leader in Department of Infectious Diseases, Southwest Hospital, Third Military Medical University in Chongqing. He graduated from Guiyang Medical College and then received his Post-graduate training at Third Military Medical University. He studied in Gifu University in Japan and then in UCSD and Johns Hopkins University. He is mainly devoted to the research on hepatitis B and C. He has been chief editor of 16 monographs, associated editor for 31 monographs and published more than 400 papers, including Gastroenterology, Hepatology and CGH. He received the 2nd Class Award of National Scientific and Technology in 2004.

Abstract:

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains a world concerned question. Despite the administration of HBIG and hepatitis B vaccines after birth, the immunoprophylaxis failure leading to significant MTCT rates ranging from 8% to 32% has been reported among HBeAg positive mothers with high HBV DNA levels. Recently, antiviral drugs, especially nucleoside analogues (NUCs), have been used in clinical studies to prevent perinatal infection. All current oral anti-HBV drugs are FDA pregnancy category C, except telbivudine (LdT) and tenofovir disoproxil (TDF) and emtricitabine (FTC), which are pregnancy category B drugs. Drugs in category B are confirmed safe to fetus in animal reproduction studies, while those in category C are not well defined. LAM was firstly used in HBV-infected mothers, and showed a satisfactory safety profile in late pregnancy. LdT and TDF has potent, specific, and selective anti-HBV activity when administered by an oral route, and no mutagenic, carcinogenic effects, appreciable embryonic or fetal toxic effects were found, especially in women during their reproductive period. In our studies, LdT and TDF have demonstrated a wonderful long-term safety profile in both mothers and their infants. They have also demonstrated an excellent efficacy—as high as 100%—in the protection rate of mother-to-infant transmission. Therefore, administration of NUCs therapy to HBV carrier mothers during pregnancy is effective in reducing MTCT. Furthermore, it is known that pregnant women are in an immune allergic status and LdT was reported to have the beneficial functions of immunoregulation in HBV-infected pregnant women.

Biography:

Wei-Ting Wang has completed her PhD from National Yang-Ming University and is now a Post-doctoral fellow in National Chiao-Tung University.

Abstract:

Chronic hepatitis C virus (HCV) infection is one of the leading causes of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). More than 130 million people are now infected with HCV worldwide. Since there is no available vaccine, HCV infection remains a serious global health problem. Recently, the HCV nonstructural protein 5A (NS5A) has emerged as a novel anti-HCV drug target and the roles of this enigmatic viral protein in HCV propagation have been largely uncovered. Although without enzymatic activity, HCV NS5A plays multiple roles in HCV propagation and participates in almost every stage of HCV life cycle, including HCV RNA replication and infectious virus production. Our recent studies have shown that the cellular protein Y-box binding protein 1 (YB-1), a known HCV cellular cofactor, interacts with and protects NS5A from rapid degradation by which YB-1 regulates the early stage of HCV RNA replication and infectious HCV virion production. Our studies then revealed that the NS5A-stabilizing activity of YB-1 is tightly controlled by a single phosphorylation of YB-1 at serine 102 which is probably mediated by HCV-infection-induced PI3K/Akt signaling. Taken together, our results have not only disclosed a probable regulatory mechanism for HCV to control the level of its own viral protein through cellular factor, but also revealed a potential strategy for developing novel anti-HCV drugs.

Biography:

Kouassi-M'bengue A is a Microbiologist, Professor of Bacteriology and Virology at UFR of Medical Sciences in Abidjan since 2008 and Head of Department of Microbiology at UFR of Medical Sciences of Abidjan since 2015. Her research areas are virological study of viral hepatitis; quality management of microbiology laboratories; antibiotic resistance. She has more than 10 publications on viral hepatitis B and C and hepatocellular carcinoma.

Abstract:

Background: Viral Hepatitis B infection is a serious public health problem. Africa and Asia are endemic with more than 8% of seroprevalence. In Asian countries like Taiwan, remarkable success in reducing long term complication has been reported by vaccination. World Health Organization guidelines advocate that the first dose of infant HB vaccine be administered in the first few days of life. However in most of sub Saharan countries, especially in Côte d'Ivoire the first dose is administered at six weeks of age. Universal infant vaccination with the hepatitis B (HB) vaccine has been implemented within Expanded Programmed Immunization (EPI) in 2003. Collaborative agreement between National hepatitis infection Control Programs and private partner had permitted to reduce cost of screening in laboratory. Objectives: This study sought to determine prevalence and factors associated with HBV in children and adults populations in Abidjan (Cote d’Ivoire). Methods: A cross-sectional study was conducted at Pasteur Institute of Cote d’Ivoire from July 2015 to February 2016. Ethical clearance for this study was obtained from National Ethical and Research Committee. We obtained informed written consent from participants of the study and administered a questionnaire related to socio demographical information and risk factors of possible route transmission HBV and HCV. Blood sample were collected for the detection of HBS Ag, Ab –HBc IgG and Ab –HCV. Serological analyses were performed by Cobas e 601 (Roche R). Data was entered into EPI INFO 3.5 and analyzed by logical R. Qualitative variables were compared using the Fisher exact test and quantitative variables by analysis of variance (ANOVA). Results: A total of 1801 patients were recruited; among them 138 children (7.7 %) aged 0 to 15 years and 1663 adults (92. 3%). Sex ratio was 1.2 (964/837). The overall prevalence of HBsAg was 30. 9% (557/1801). Concerning children 12.3% (17/138) were HBs Ag-positive. About HCV, the overall prevalence rate was 5.3% (95/1687), no child was HCV positive. Co- infection HBV /HCV rate was 0, 95% (16/1687). Undertaking age, blood transfusion, sharing of needle were associated with HCV (P=0.01). HBV was associated with sex, youth, promiscuity, low socio economical level, tattooing ((P<0.001; p<0.001; p=0.007; p=0.01; p=0.002). Conclusion: Our finding shows a high prevalence of HBV and measures to reduce the disease and transmission burden must be introduced.

Biography:

Deepak Bansal has completed his fellowship (DM) in Gastroenterology in 2015 from Dayanand medical college and hospital, Ludhiana, India and is presently serving as Assistant Professor in department of gastroenterology at government medical college and hospital, Chandigarh, India. He has participated and organized several gastroenterology conferences and has special interest in field of hepatology.

Abstract:

Liver fibrosis predicts presence of portal hypertension. Fibroscan which is based on transient elastography measures liver stiffness. Our study was conducted to evaluate whether fibroscan can effectively predict the presence of portal hypertension and of esophageal and gastric varices in patients with cirrhosis. We prospectively enrolled 201 patients with established case of cirrhosis between January 2013 and June 2014. Fibroscan was measured for each patient and additionally upper GI endoscopy was done. Results showed that 182 (91.9%) patients had evidence of portal hypertension with mean fibroscan value of 30.01± 22.15 kpa and 16 patients had no evidence of portal hypertension on upper GI endoscopy with mean fibroscan value of 18.93+/-18.26kpa ( p value=0.050). The mean fibroscan value of patients (53/102) with high grade oesophageal varices was 40.81±22.88kpa. Subgroup analysis shows that fibroscan can predict high grade oesophageal varices (grade II + III vs. grade I) (p value=0.008). The cut off value of fibroscan for detection of portal hypertension was 29.37kpa, with 94.59% sensitivity. This indicates that fibroscan is a very useful test for detection of portal hypertension. Cut off value of fibroscan, for presence of high grade varices was 38.54kpa with negative predicted value of 81.46% which indicates fibroscan can effectively predict presence or absence of high grade oesophageal varices and thus upper GI endoscopy applied selectively to the patients. Thus, our study shows that fibroscan is very useful non-invasive test for detection of portal hypertension and predicting high grade oesophageal varices.

Biography:

Kouassi-M'bengue A is a Microbiologist, Professor of Bacteriology and Virology at UFR of Medical Sciences in Abidjan since 2008 and Head of Department of Microbiology at UFR of Medical Sciences of Abidjan since 2015. Her research areas are virological study of viral hepatitis; quality management of microbiology laboratories; antibiotic resistance. She has more than 10 publications on viral hepatitis B and C and hepatocellular carcinoma.

Abstract:

Background: The mechanism underlying the transition from simple steatosis to the more severe form NASH remains unclear thus far. Aim: To investigate the lipidomic profile alteration during the transition of non-NASH to NASH in human livers, and to identify hepatic lipid biomarkers which can discriminate between NASH and non-NASH liver samples. Materials & Methods: Two independent sets (n=119 and n=106) of liver tissue samples collected from transplantation donors without heavy alcohol intake and viral hepatitis were characterized for histology. Lipidomic profiling was conducted for both sample sets. Liver tissues were classified as non-NASH or NASH. For lipidomic analyses, we use the first set as a discovery set (n=119) and the other as a validation set (n=106). A multivariate analysis was performed to identify lipids that discriminate NASH and non-NASH samples accurately. Elastic net logistic regression along with 10-fold cross validation was used. Validation was conducted using lipidomics data of 106 liver tissue samples obtained independently from another data set. Results: We found that 75 phospholipids are significantly different between NASH and non-NASH samples in the discovery set (p<0.01), among which 52 (69%) remained significant in the validation set (p<0.05). The majority of these lipids are phosphatidylcholines (PCs) and ester phosphatidylcholines (ePCs). 10 lipids (p<0.01) were found to discriminate NASH versus non-NASH accurately, with an AUROC (Area Under the Receiver Operating Characteristic) curve = 0.89. The same 10-lipid signature produced an AUROC of 0.92 in the validation set, with 3 lipids remained significant (p<0.05). By focusing on these 3 lipids that are significantly associated with NASH in both sets, we observed an AUROC of 0.83 and 0.82 in the discovery and validation data set, respectively. Conclusion: Our study highlighted the important role of phosphatidylcholines in the development of NASH. Further investigation of these lipids among larger biopsy-proven NASH samples as well as in serum samples are warranted.

Biography:

Mohamed Abdel Samiee is a hepatologist at National Liver Institute in Menoufiya University, Egypt.

Abstract:

Background: Transient Elastography (TE) is a non-invasive and reproducible tool to assess liver fibrosis/cirrhosis. However, it remains to be determined if ALT flare interferes with fibrosis assessment. Aim: To determine the effect of increased serum ALT on liver stiffness measurement in patients with acute viral hepatitis. Methods: Thirty consecutive patients with acute hepatitis of virus etiology with elevation of liver enzymes (>10 folds of ULN) were prospectively included. Blood samples were collected and TE was done initially and after resolution of hepatitis and after normalization of liver enzymes. Patients with high BMI which could affect fibroscan and patients with cirrhosis were excluded. For determination of the etiology of hepatitis, a detailed physical examination, history taking and laboratory tests were performed in all patients. Results: Patients were 32.87±10.2 years old and males were 14 (46.7%). In all patients, the degree of liver stiffness at the time of the peak increase in aminotransferases exceeded the cutoff values proposed for the prediction of significant fibrosis or cirrhosis. The mean value of LSM at the time of inclusion in the study was 13.91±6.7 kPa and the mean value of LSM after resolution of hepatitis was 7.7±3.08 kPa. A progressive significant reduction in liver stiffness values was observed (P<0.01) in the follow-up period in parallel with the reduction of ALT levels (P<0.01). Moreover, a statistically significant, positive correlation between ALT and LSM at the onset of acute viral hepatitis was found (r=0.38, P<0.05). No significant correlation was found between increased total bilirubin level and LSM (r=0.3 and P>0.05). Reduction of mean value to 6.21±1.14 kPa was observed in 10 patients after 1 year of ALT normalization. Conclusion: TE has not demonstrated reliable diagnostic accuracy in patients with acute viral hepatitis.

Biography:

Md Kamrul Hasan Chowdhury has completed his Bachelor of Pharmacy from the University of Development Alternative (UODA), Bangladesh. Following his Bachelor’s degree, he has received a scholarship for studying Master of Science (MSc) in Pharmacogenomics at Inje University, College of Medicine, South Korea. After graduating from Inje University, he successfully obtained a competitive PhD Scholarship UIPA (University International Postgraduate Award) from the University of New South Wales Australia, Australia.

Abstract:

Recently it has been found that glucagon is able to activate the β-catenin signaling pathway leading to increased cyclin D1 and c-Myc expression in liver. Therefore, the main aim of this study is to determine if the effect of glucagon activating β-catenin signaling leading to increased target gene expression is mediated through cAMP activation of protein kinase A. Primary rat hepatocytes were incubated with insulin, glucagon or epinephrine and a range of inhibitors of PI 3-kinase, Wnt, mitochondrial uncoupler (niclosamide) or PKA inhibitors to dissection out the pathway leading to increased serine 552 phosphorylation of β-catenin following glucagon exposure. Western blot and real-time PCR were used. In primary rat liver cells, we found that short exposure of glucagon or epinephrine caused a rapid increase in serine-552 phosphorylation on β-catenin that leads to increased cyclin D1 and c-Myc expression. Both glucose and insulin had no effect on this pathway. A range of PI 3-kinase and Wnt inhibitors were unable to block the effect of glucagon phosphorylating β-catenin. Interestingly, both niclosamide and the PKA inhibitor H89 blocked the glucagon effect on β-catenin signaling leading to a reduction in the target genes expression. We have identified a new pathway via glucagon signaling that leads to increased β-catenin activity that can be reversed with the antihelminthic drug niclosamide which has recently shown promise as a potential treatment of type-2 diabetes (T2D). This novel finding could be useful in liver cancer treatment particularly in the context of T2D with increased β-catenin activity.

Biography:

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Abstract:

Libya is one of the countries where hydatid disease is endemic. A team of doctors reviewed retrospectively a total of 400 patients with hepatic hydatid cysts and were operated at Zliten University Hospital over the period of 24 years. The team of doctors looked for the clinical presentations of hepatic hydatid cysts. Most patients experienced abdominal pain or abdominal mass and few patients came to surgery department with rare presentation like obstructive jaundice. The obstruction of common bile duct was caused by the big cyst compressing on the bile duct or by the daughter cysts or hydatid membrane went into the bile duct. 49 patients whose main presentation involved abdominal pain and jaundice had been subjected for ultrasound scan and CT scan. All had open surgery, with two patients dying due to multiorgan failure, four patients developed recurrence of the hydatid, seven patients had bile leak which stopped spontaneously and three patients developed wound infection. All patients were cured from jaundice by surgery. In this presentation, the author would like to present new technique for common bile exploration in case of hydatid induced obstructive jaundice.

Biography:

Ansoumane Kourouma has completed his PhD from Huazhong University of Sciences and Technology and Master’s degree in Biotechnology from University of Oriente, Santiago de Cuba, Cuba. He is a Lecturer in Toxicology at University of Gamal Abdel Nasser of Conakry, Guinea. He has published more than 10 papers in reputed journals and has participated in several conferences and workshop.

Abstract:

An emerging literature suggests that early life exposure to 4-nonylphenol (4-NP), a widespread endocrine disrupting chemical, may increase the risk of metabolic syndrome. In this study, we investigated the hypothesis that intraperitoneal administration of 4-NP induce hepatic steatosis in rat. 24 males Sprague-Dawley rats were administered with 4-NP (0, 2, 10 and 50 mg/kg b.wt) in corn oil during 30 days. Liver histology, biochemical analysis and gene expression profiling were examined. After treatment, abnormal liver morphology and function were observed in the 4-NP-treated rat, and significant changes in gene expression as indicator of hepatic steatosis and apoptosis were observed compared with controls. Up-regulated genes involved in apoptosis, Hepatotoxity and OS, increased ROS and decrease of antioxidant enzyme were observed in the 4-NP exposed rat. Extensive fatty accumulation in liver section and elevated serum SGOT, SGPT, LDH and γ-GT were also observed. Incidence and severity of liver steatosis was scored and taken in to consideration (steatosis, ballooning and lobular inflammation). Hepatocyte apoptosis could promote NAFLD progression; Fas/FasL, TNF-α and Caspase-9 mRNA activation were important contributing factors to hepatic steatosis. These findings provide the first evidence that 4-NP affects the gene expression related to liver hepatotoxicity, which is correlated with hepatic steatosis.