International Congress on Viral Hepatitis July 20-30, -0001 Florida, USA

Ekaterina Liusina is currently a PhD fellow in Gastroenterology. Her professional interests include Portal hypertension, Viral hepatitis, Liver cirrhosis and Statistical methods in medicine. She is the member of Russian Scientific Liver Society, Russian Gastroenterology Association and European association for the study of the liver.

Background: Elimination of the etiological agent responsible for the progression of chronic liver injury has been shown as one of the important prognostic factor for survival in cirrhotic patient. Portal hypertension is a main complication of liver cirrhosis. Measurement of hepatic venous pressure gradient (HVPG) is currently recommended for detection of portal hypertension but its wide use in the clinical practice is limited by its expensiveness and invasiveness. Colecchia et al. in 2012 published predictive model for HVPG values included spleen (SS) and liver stiffness (LS) measured by transient elastography in cohort of patients with HCV-related liver cirrhosis. Aims: To establish the prognostic predictive value of HVPG model (calculated with SS and LS) for presence of esophageal varices and risk of bleeding. To evaluate clinical significance of spleen and liver stiffness measurements in 3 cohort of patients: HCV-related cirrhosis before and after antiviral treatment, HCV-related liver cirrhosis follow-up and in patients with alcoholic cirrhosis before and after period of abstinence. Methods: We plan to enroll consequently in the study one hundred patient with HCV and alcohol-related cirrhosis. Patients undergo baseline blood test sampling, upper endoscopy for detecting esophageal varices, ultrasound, liver stiffness measurement with Fibroscan (LS), spleen stiffness measurement with Fibroscan (SS) during a week of hospitalization. HVPG calculates according to predictive model HVPG =-4.44+0.241LS+0.226хSS. For all patient with alcoholic cirrhosis will be given recommendation for abstinence. HCV-patient who will meet inclusion criteria will be treated in clinical trials with different antiviral regimes. All baseline procedures will be repeated in 6-12 month after baseline. Complication during follow-up period will be registered. At the moment enrolled 41 patients (26 patients with HCV – related cirrhosis, 15 patients with alcoholic cirrhosis) Results: LS and SS in the group with varices are significantly higher than without (p=0.003). Median of LS in varices group is 32.4 kPa (IQR 24.8-48) vs. 20.6 kPa (IQR 16.9 – 27.5). Median of SS in varices group is 58.2 kPa (IQR 38.6-75) vs. 36.3 kPa (IQR 29.4-63.9). Levels of portal pressure calculated with predictive model are significantly higher: in varices group (p=0.009) is 16.8(IQR 11-23) vs. 9.4 (IQR 7-13) respectively. Sensitivity HVPG predictive model for detection EV is 92%, specificity is 61%. For predicting esophageal varices in our group (regardless etiology) PPV is 83%, NPV is 80%, LR+ 2.3, LR-0.14 respectively. In addition a statistically significant difference is observed when compare patients with alcohol-related cirrhosis (median LS is 45,4kPa (IQR 25-75) to HCV-related group (median LS is 24 kPa (IQR 16-27) (p=0.004). Conclusion: We plan to investigate the diagnostic test accuracy of HVPG predictive model for esophageal varices depending on the etiology of liver cirrhosis (HCV or alcohol) in separate.

Dr. Shi-Bing Su, Medicine Doctor (Ph.D.-medicine), is a Professor of Integrative Medicine and Traditional Chinese Medicine (TCM), director of the center for complex systems, Shanghai University of TCM, leading scientist of TCM System Science Discipline, distinguished researcher of Shanghai TCM internal Medicine E-institute, visiting professor of Nanjing University of TCM, guest professor of Henan college of TCM, academic Journal editor for Integrative Medicine International, Journal of Integrative Medicine, Journal of TCM Science, etc. He got his B Sc in TCM at Nanjing University of TCM, M Sc in Pharmacy and Medicine Doctor degree in Gastroenterology at Cancer Institute, Kanazawa University, and Docent at China Pharmaceutical University. Currently Dr. Shi-Bing Su research focus on TCM syndrome classification-based treatment in clinical and basic studies applied by system biology. He has published 160 papers and 10 books in academic Journals.

Background: Liver cirrhosis is a critical state in the natural course of hepatocellular carcinoma (HCC). Chronic hepatitis B (CHB) is a major cause of liver cirrhosis in China. To find biomarkers for the diagnosis of CHB caused cirrhosis (HBC), we examined the cytokines profiling of CHB and HBC. Methods: Serum samples of 15 health controls (HC) and 15 CHB patients and 15 HBC patients were collected to detect the profiles of 48 cytokines by multiplex biometric ELISA-based immunoassay. Partial least squares discriminant analysis (PLS-DA) was used to analyze the significant cytokines, and they were validated using independent cohort of 60 CHB patients, 60 HBC patients and 35 HC samples. Results: There were 22 differential expressed cytokines of CHB and HBC. Three differential expression cytokines including interleukin (IL)-9, IL-2 receptor subunit alpha (IL2Rα) and Granulocyte-macrophage colony-stimulating factor (GM-CSF) were found by PLS-DA, and their significant changes of serum levels were further validated. The Receiver-operator characteristic (ROC) analysis demonstrated that three cytokines and their logistic regression panel potentially to be the potential biomarkers for CHB and HBC differentiation (P<0.001, AUC=0.876). Furthermore, a functional pathway analysis showed that differential regulation of cytokine production in macrophages, T Helper Cells and intestinal epithelial cells by IL-17A and IL-17F were enriched in the 22 differentially expressed cytokines. They were also enriched in pathway of hepatic fibrosis / hepatic stellate cell activation. Conclusions: There were particular cytokines profiles of CHB and HBC. Besides, IL-9, IL2Rα and GM-CSF may be involved in the differentiation of CHB and HBC.These findings may give further insight into the pathobiology of HBC.

Chiou-Hwa Yuh has completed her PhD from National Yang-Ming University in Taiwan, and Postdoctoral studies from California Institute of Technology in USA. She was famous in Developmental Gene Regulatory Networks. She initiated the systematic analysis of hepatocellular carcinoma (HCC) in mouse model, and established transgenic zebrafish model. She further developed the drug screening platform to identified novel small molecules which are effective in treatment HCC and lower toxicity compared to Sorafenib. She has published 41 papers in reputed journals and has been serving as an editorial board member of repute journals.

The formation of hepatocellular carcinoma (HCC) is a chronic progress including hepatitis, steatosis, fibrosis, cirrhosis. Liver cancer is the third most common cancer worldwide and ranked as a leading cause of mortality in Taiwan. Traditional chemotherapy and radiation has poor effectiveness for the treatment of liver cancer patients, for the target therapy, Sorafenib is the only one approved by FDA which can inhibit liver cancer and prolong life. The development of new target therapy is therefore urgently needed. Previously, we have used the HBx-induced HCC mouse model and identified four common regulators (Src, Edn1, Bmp4 and Bmp7) which can be used as molecular targets for HCC treatment. Furthermore, we have established the transgenic fish overexpressing HBx or src in the p53 mutant, and edn1 transgenic zebrafish developed into HCC. Those transgenic fish developed steatosis, hepatitis, fibrosis before cancer formation. The HCC from those transgenic zebrafish is much more similar to human HCC in histopathology or the pattern of gene expression, which allow them more suitable as drug screening platform to identify the drugs to effectively treat human liver cancer. In this report, I will demonstrate the advantage of zebrafish HCC model as well as zebrafish embryos. We have developed a high-throughput drug screening platform to identify novel and safe anti-HCC therapeutic means to save more life. In addition, due to the heterogeneity of HCC, there are no effective clinical tests that can predict the effectiveness of the anti-cancer agents for patients. Using patient-derived xenograft zebrafish model, we are able to identify personalized medicine for the future use in clinical therapy.

Maha Mohsen Hussein is currently working as an Assistant Professor of Hepatology and Gastroenterology, Ain Shams University. Graduated with honor in 1998 from Faculty of Medicine, Ain Shams University. Had Master Degree in 2002 with a research on (Relationship between Gastric and Gallbladder Empting in Patients with Non Ulcer Dyspepsia Positive for Helicobacter Pylori) and MD Degree in 2007 completed by research on (Relation between aflatoxin B1 level and glutathione antioxidant in chronic hepatitis C patients with and without hepatocellular carcinoma). Worked since graduation in Ain Shams University; Residency then Assistant lecturer at 2003, Lecturer at 2007 and Assistant professor since 2012 till now. Joined liver transplantation team of Ain Shams Hospitals since 2008 till present as transplant hepatologist and had observer ship in the Transplantation Center of Methodist Hospital in Texas in USA 2009. Worked as a member of national team for prevention and treatment of viral hepatitis 2007-2010.

Reports in recent years have indicated that saliva represents an increasingly valuable resource for disease diagnostics including periodontal diseases as well as different types of cancer, cardiovascular, endocrine, immune and hereditary diseases. In contrast to blood pH which is under tight control, salivary pH shows variability depending on a wide range of factors reflecting its potential variability in chronic health status. In this study, we investigated the potential role of salivary pH to reflect the state of chronic metabolic acidosis in patients with hepatocellular carcinoma. Salivary pH was measured in 300 subjects using narrow range pH strips. Subjects were divided into 3 groups, group I consists of 100 healthy volunteers, group II consists of 100 patients with liver cirrhosis and group III consists of 100 patients with HCC. Results showed a significant difference (P≤0.05) in salivary pH values between the three groups with the HCC group being the most acidic (mean value of 5.62) followed by the cirrhotic group (mean value of 6.24). The control group showed normal salivary pH (mean pH value of 6.6). The predictive performance of salivary PH as an indicator of hepatic malignancy among the 100 patients of HCC shows that the salivary pH level at a cut off value of ≤5.85 gives a sensitivity of 80% and a specificity of 84%. The non invasive and economically sound nature of this test makes it a potential auxillary test in screening for HCC.

Tari M.A. George Michael is currently working as an Assistant lecturer in Ain Shams University in the department of Gastroenterology and Hepatology. Graduated from faculty of medicine, Ain Shams University in 2006 with honors, worked as a resident in Ain Shams University hospitals till 2012 then promoted to Assistant lecturer in the same university in 2013. Completed her Master's degree in 2011 with honors with a research on the "Hemostatic changes in liver cirrhosis". Completed 2 parts of the MRCP certificate in Internal medicine. Completed first part of the MD and a thesis on "Factors affecting platelet count after liver transplantation", and preparing for the final part of the MD. Took part in the endoscopy training in association with Hull University in UK and is currently in the Ain Shams University center for endoscopy.

Thrombocytopenia is one of the common features of advanced liver cirrhosis. Liver transplantation is the only treatment for end stage liver disease, but even after transplantation thrombocytopenia is frequent. The aim of this study was to monitor platlets count and to identify factors contributing to persistence of thrombocytopenia following liver transplantation. The study included 36 patients who underwent LDLT in Ain Shams Center of Organ Transplantation (ASCOT) in one year (2013). Preoperative platelet count was recorded. Following transplantation, platelets count was recorded daily for the first two weeks, then at one month, 3 months, 6 months and 12 months. Splenic size and portal venous blood flow was measured at the same intervals by Doppler ultrasound. Thrombopoietin was measured before surgery then at 2 weeks and 6 months following transplantation. Persistent thrombocytopenia was defined as a platelet count less than 150 x 109/L at one year post-transplantation. At the end of the study, 56% of patients had persistent thrombocytopenia at 1 year. Factors that showed significant correlation with persistent thrombocytopenia were lower preoperative platelet count, lower preoperative portal vein flow velocity, greater preoperative spleen size, higher GRWR and longer operative time. Highest sensitivity was found for preoperative portal flow velocity and highest specificity was to GRWR. HCV recurrence, rejection episodes, CMV infection, biliary and vascular complications post operative were not independent factors for persistent thrombocytopenia.

Simone Famularo graduated from Sapienza University School of Medicine, Rome, Italy. He was trained as a surgeon for four years and was a research fellow in cancer in the hospital of that same university. He won a research fellowship at Royal Marsden Hospital in London, working on the “Small for Size Syndrome” after major hepatectomy. He has published an article regarding this, and currently he is continuing his research on the syndrome in Sapienza University of Rome, focusing on the pathophysiological mechanism of small for size after extended hepatectomy. He cooperates with several international journals as a reviewer.

Background: Small-for-size syndrome is an acute liver failure which occurs in small-for-size grafts after living donor liver transplantations, and after major liver resections, usually assessed on or after the day 5 postop. Up to 35% of patients undergoing major hepatectomy can develop the syndrome. It consists in hyperbilirubinemia, coagulopathy, and increased portal vein pressure, due to an overflow in the portal microvascular bed respect to the liver remnant’s size. Case Reports: Three cases of patients who underwent major liver resections for liver metastasis are presented. All three developed small for size syndrome, with continuous improvement of bilirubin serum levels, and GGT. All the patients have been checked for portal vein wedge pressure, demonstrating hypertension in the portal vessel bed. To cure the syndrome, we report the use of treatments usually used in liver transplantation to avoid small-for-size-syndrome, such as Splenic Artery Embolization and Octreotide, focusing our approach on overflow and over-pressure, with different size remnants. Conclusion: Whilst literature is focused on prevention of SFSS in case of living donor liver transplantation, there is not enough evidence about how to treat patients who undergo extended hepatectomy. We report a completed rehabilitation of each case, suggesting a prevalent role of the blood flow and pressure parameters with different size remnants, according to the most recent evidence in the pathophysiological underlying mechanism.