3^rd World Congress on Hepatitis and Liver Diseases October 10-12, 2016 Dubai, UAE

Andreas Christe has obtained his Medical education and Residency in Pathology and Radiology at the University of Bern, Switzerland, Post-doctorate Fellowship at the Department of Radiology at Stanford University, California from 2008 to 2010 which was funded by the Senior Investigator Grant SSMBS (Swiss National Science Foundation). Since 2010 he is the Chief of Body CT at the Department of Radiology, Inselspital at the University of Bern and received in 2012 the Venia Docendi award in Radiology (Habilitation).

Background & Aims: Computer tomography imaging with arterial enhancement fraction (AEF) uses a tri-phasic CT image acquisition (unenhanced, arterial, portal venous phase) to generate color coded CT-images. The purpose of this study was to investigate if the use of the AEF imaging would supersede the acquisition of a fourth contrast phase (equilibrium phase) and thus allow a 25% reduction of radiation dose. Materials & Methods: 55 patients who underwent liver transplantation between 2010 and 2013 and who had a CT scan acquired in four contrast phases (unenhanced, arterial, portal venous and equilibrium phase) on a Siemens Somatom Sensation 64 were included: 35 patients with 108 histologically proven HCC, as well as 20 patients without HCC-lesions. 47 lesions were already treated by prior TACE. AEF was calculated using the syngo.via workstation (Siemens, Erlangen, Germany): AEF=[(HUA-HUU)/(HUP-HUU)]×100, where HU is the attenuation, A is the arterial phase, P is the portal phase and U is the unenhanced scan. A total of 6 radiologists read the tri-phasic grayscale images in conjunction with the color AEF-maps. For the second read-out, three readers looked at the CT images with four contrast phases and three readers only at three contrast phases (without equilibrium phase). Results: The JAFROC analysis showed a significant difference of the figures of merit (θ) between the tri-phasic read-out without (θ=0.718) and with the AEF-maps (θ=0.750, p=0.0007). Diagnostic performance with four-phases (θ=0.775) was significantly better than with tri-phases (θ=0.718) without using the AEF-map (p=0.0018) but not different from the tri-phasic CT with the AEF-maps (θ=0.750, p=0.3053). Sensitivity of tri-phasic CT was 36.4% (95% CI: 32.5% to 40.5%) and PPV was 76.5% (95% CI: 71.0% to 81.4%). With the AEF-maps sensitivity and PPV increased to 49.7% (95% CI: 45.6% to 53.9%) and 83.4% (95% CI: 79.0% to 87.1%), respectively. Lesions with and without prior TACE treatment were detected with a sensitivity of 31.9% and 42.3% without the use of the AEF map and with a sensitivity of 48.4% and 51.6% with the AEF map. A normalized AEF cut-off value of 70% for small lesions (<1 cm) and 60% for larger lesions (≥1 cm) lead to highest HCC-accuracy. Conclusion: In HCC CT-screening the fourth equilibrium phase could be replaced by the calculated AEF-maps. This allows a 25% reduction of radiation dose, which is relevant for patient undergoing repetitive HCC-screening.

Arida Buivydiene was graduated from Vilnius University Faculty of Medicine in 1992 and has completed Gastroenterology Residency studies at Faculty of Medicine of Vilnius University in 1997. She is currently pursuing Doctoral (PhD) studies at Vilnius University, Faculty of Medicine. She is responsible for the liver recipients and takes care of the patients before and after liver transplantation.

Aim: To evaluate whether testing of IL28B SNPs in rs12979860 and rs8099917 regions and UCKL-1 expression in liver biopsy improves the forecasting of hepatocellular carcinoma (HCC) development risk in patients with HCV cirrhosis. Patients & Methods: 32 patients (age of 32-70 years) with cirrhosis of HCV etiology were tested. Out of them, in 21/65.5% HCC was diagnosed (I group), 11/34.4% patients had no HCC (II group). The rs12979860 and rs8099917 SNPs were detected by single-nucleotide extension method. UCKL-1 expression was visualized by immunohistochemistry staining with polyclonal rabbit anti-UCKL-1 antibodies and EnVision G2 double staining system. Results: Significant difference in SNP rs8099917 was found in studied groups, p=0.025. HCC was more frequently diagnosed at rs8099917 T/T (large homozygous SNPs) as compared with non-T/T (61.9% vs. 18.2%, p<0.05). The HCC risk correlates with bright UCKL-1 staining (p=0,004, r=0,491). In cases of combination of intense UCKL-1 expression with rs12979860 C/C and rs8099917 T/T or T/G, the risk of HCC increases 8.444 times (p=0.046, R²=0.516, χ²=14,961, p=0.001). Regardless IL28B SNPs, in II group UCKL-1 expression was significantly lower. Conclusions: Bright UCKL-1 expression in combination with IL28B rs12979860 C/C together with rs8099917 T/T or T/G 8.444 times increases risk of HCC developing patients with cirrhosis of HCV etiology.

Ali Rahman has completed his MD and MSc from Johannes Gutenberg University, Mainz in Germany and Postdoctoral studies from the University of Bern in Switzerland. He is currently a Consultant in Radiology and Neuroradiology (emphasis in Neuro, Abdominal and MSK Radiology.

Our study included data of 244 patients (Average age 39.1 years, 55.7% men, 44.3% female) with chronic hepatitis C (HCV genotype 1 to 4). In addition to many demographic characteristics also laboratory parameters (ALT, AST, g-GT, bilirubin, Quick) and hepatitis-related parameters (hepatitis C viral load, validation of hepatitis A or/and B and duration/type of the anti- HCV therapy) were obtained. From 186 patients grade of liver fibrosis was determined after METAVIR. Fibrosis abundance and rate of liver fibrosis progression were determined. These parameters were related to chosen genpolymorphism of IL-10 (G/A -1082; C/T - 819; -592 C/A), rate of fibrosis progression and prevalence of fibrosis. The IL-10 G/A -1082 genotypes AA, GA and GG showed no difference in prevalence of liver fibrosis (74.4 to 85.2%), the rate of fibrosis progression and the relative risk fibrosis (1.04 to 1.11 FACh increases) detectable. At IL-10 C/T -819, the three genotypes TT, CT and CC showed no difference in the rate of fibrosis. However, the fibrosis progression in TT was 1.5 fibrosis-classes per year higher than CT (0.9) or CC (1.1). The relative risk for liver fibrosis did not differ (1.09 to 1.15 FACh). The IL-10 C/A -592 Genotype CA led the least likely to liver fibrosis (68.5%), while patients with CC (82.5%) and AA genotype (88.2%) more often developed a liver fibrosis. The AA genotype led to a higher fibrosis progression rate (1.6 fibrosis classes/year) than the CA (0.9 classes) or CC genotype (1.1 classes). However, the relative risk of fibrosis was 0.93 times lower than the CC genotype compared to AA.

Jisoo Park has completed her Master degree from Sookmyung Women's University and has experience of cellular signaling in the terminal differentiation of keratinocyte. She has then moved to University of Cincinnati, Ohio, USA and worked as a Research Associate in the lab of Prof. George Thomas to learn the cellular signaling of mTOR/S6K1 pathway in the field of energy metabolism by using animal models. She returned back to Korea to obtained PhD in the field of Energy Metabolism at the Department of Pharmacology, College of Medicine, Chungnam National University. She is currently investigating the putative roles of PHF20 in the regulation of glucose metabolism. She has published 9 papers in reputed journals including Metabolism, Cellular Signaling and Head & Neck.

The importance of PHD finger protein 20 (PHF20) in the cellular process is recently emerging as a regulator for the p53 and NF-kB signaling. In this study, we have provided the clear evidence that PHF20 exhibit the novel function in hepatic steatosis by regulating lipogenic genes. Transgenic (TG) mice with PHF20 expression are glucose intolerant; however the insulin sensitivity of peripheral tissue in PHF20 TG mice appeared to be unaffected. Interestingly, the total contents of insulin amount in pancreatic islets and the glucose stimulated-insulin secretion of isolated islet were reduced in PHF20 TG mice compared to wild type mice, indicating that the phenotypic characteristics of PHF20 mice with glucose-intolerance is due to the lack of insulin production/secretion in pancreatic beta-cells in PHF20 TG mice. Administration of PHF20 TG mice with high fat diet for 8 weeks leads to increase the body weight compared to control mice. By screening the profile array of transcription factor activation with PHF20, SREBP1 was found to be activated by PHF20 overexpression in HeLa cells. Chromatin-immunoprecipitation analysis revealed that PHF20 directly bind the promoter of SREBP1. Furthermore analysis of quantitative PCR with liver tissues from PHF20 TG mice showed the up-regulation of SREBP1 target genes. Taken together, PHF20 appears to be positive regulator for lipogenesis and PHF20-mediated SREBP1 up-regulation is responsible for the accumulation of hepatic lipid, leading to weight gain phenotype. Thus, this study provided the new concept for glucose metabolism and novel pharmacological target in obesity.

Hyunji Lee is currently a Masters student at the Metabolic Disease and Cellular Signaling Laboratory, Department of Pharmacology and Medical Science, College of Medicine, Chungnam National University, South Korea. She has recently published her first paper in "Clinical Interventions in Aging".

Alcohol-induced liver injury is the most common liver disease in which fatty acid metabolism is altered. It is thought that altered NAD+/NADH redox potential by alcohol in the liver cause fatty liver by inhibiting fatty acid oxidation and the activity of tricarboxylic acid cycle reactions. Tabebuia avellanedae extract (TAE), a naturally occurring quinone, has been shown to stimulate fatty acid oxidation in an obese mouse model by activating adenosine monophosphate-activated protein kinase (AMPK). In this report, we clearly show that TAE reduced alcohol-induced hepatic steatosis and induced fatty acid oxidizing capacity in ethanol-fed rats. TAE treatment markedly decreased hepatic lipids while serum levels of lipids and lipoproteins were increased in rats fed ethanol-containing liquid diets with TAE administration. Furthermore, inhibition of lipolysis, enhancement of lipid mobilization to mitochondria and up-regulation of mitochondrial β-oxidation activity in soleus muscle were observed in ethanol/TAE-treated animals compared to the ethanol-fed rats.

Ali received the bachelor of Clinical Laboratory Sciences, College of Applied Medical Sciences from King Saud University in Riyadh, KSA in 2005 and the master degree of Laboratory Medicine from RMIT university in 2010, a master research in the Cytogenetics and Molecular Cytogenetics Laboratories of the Murdoch Children Research Institute in Melbourne. He worked as medical technologist 1 in biochemistry lab in King Fahad Medical City 2006-2008 and 2011. His work involved the testing of quality control of the automated machines, blood sample for clinical chemistry, liver and lipid profile tests. He is currently a PhD at rmit university, and A lecturer in the Laboratory Medicine department at Al-Baha University. Ali current research interest in the evaluation of effectiveness and safety of Chinese medicine in the treatment of non-alcoholic fatty liver disease and liver-related disease. The common research topics include molecular biology, metabolic syndrome, diabetes and biochemistry.

Background & Aim: Hepatosteatosis is the excess lipid deposition within hepatocytes and this is closely associated with type-2 diabetes (T2D). Matrine (Mtr) is a small molecule drug used in humans for the treatment of chronic viral infection in the liver where increased de novo lipogenesis (DNL) often exists. Hepatosteatosis can be induced by DNL promoted by endoplasmic (ER) stress. The aim of this study is to investigate the effect of Mtr on hepatosteatosis induced by DNL and on glycaemic control in T2D. We hypothesized that the hepatoprotective drug matrine may be repurposed for the treatment of hepatosteatosis by suppressing ER stress-associated DNL. Methods: Male C57BL/6J mice were used in the present study. DNL-induced hepatosteatosis was produced by a high fructose (HFru) diet for 8 weeks. Mtr (100 mg/kg/day in diet) was administered in the last 2 weeks. Blood glucose, plasma insulin and glucose tolerance test (2.5 g/kg, ip) were assessed after 5-7 hours of fasting. T2D was generated by a high fat diet (10 weeks) plus five consecutive low doses (40 mg/kg ip) of streptozotocin with or without of Mtr (100 mg/kg/day). Findings: Matrine attenuates the increased expression of DNL pathway in HFru-fed mice. Also, matrine decreases ER stress and increases HSP72 in the livers of HFru-fed mice. In addition, matrine reduces hepatic lipid accumulation and expression of SREBP-1c in T2D mice. Summary: In HFru-fed mice, matrine reduces hepatosteatosis by inhibiting ER stress and the DNL pathway. These effects are associated with increased expression of HSP72 in the liver by interaction with HSP90. In T2D mice, matrine reduces both hepatosteatosis and hyperglycaemia. Conclusion: Matrine may have the potential to be repurposed for the treatment of T2D due to its beneficial effects on hepatosteatosis and hyperglycaemia. Matrine treatment up-regulates the expression of HSP72 in the liver. HSP72 may decrease the expression of SREBP1c and suppress lipogenesis and ER stress pathways. The overall result is a reduction of lipid accumulation in the liver, thus alleviates the glucose intolerance and fatty liver induced by HFru feeding.