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

Kassem Faraj is a third year medical student at Oakland University William Beaumont School of Medicine. He has BS in Chemistry from Wayne State University. He has been involved in research projects in the fields of urology, general surgery and internal medicine.

Acute cholangitis (AC) is an infection of the biliary tract caused by biliary obstruction and stasis. The most common symptoms are fever and abdominal pain, which are seen in 80% of patients. A 47-year-old male presented with a three-week history of scleral icterus, dark urine, and pale stools, consistent with jaundice. He complained of fatigue, but denied any abdominal pain, fever, chills, nausea or vomiting. Laboratory results were significant for AST 959 IU/L, ALT 1563 IU/L, alkaline phosphatase 199 IU/L, total bilirubin 24.0 IU/L, direct bilirubin 19.9 IU/L, total iron 246 mcg/dL, ferritin 5008ng/mL, and transferrin saturation 85%. An acute hepatitis panel was negative, and an abdominal ultrasound and CT scan were unremarkable. Serology results for EBV included: IgG 279, EB-EA (early antigen) >150, EB-NA (nuclear antigen) 544 and a normal IgM. Reactivation of EBV was suspected and a diagnosis of EBV hepatitis was made. The patient did not improve with supportive measures, prompting a liver biopsy, which showed acute inflammation, periportal fibrosis, and neutrophillic infiltration and cholestasis of the biliary tree, which was consistent with AC. MRCP was unremarkable for biliary dilatation. The patient was managed supportively and gradually improved. This case presented major challenges to clinicians including the lack of classic symptoms and biliary dilatation on imaging, the apparent iron overload and the presence of a recent EBV infection. Biliary dilatation is very common, but is not necessary for the diagnosis of AC. Mild cases can be managed with close observation.

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.

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.

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.

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.

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.