Day 1 :
Keynote Forum
Hani Oweira
Hirslanden Group, Zurich
Keynote: Surgery of the Liver and Intra-operative Interventions. What is possible Today?
Time : TBA
Biography:
Dr Hani Oweira is a specialist in surgery and bowel surgery and works as a visiting surgeon at the Andreas Hospital, Cham, Zug and as an associated partner at the Surgical Centre, Zurich. He completed his medical training and specialist qualification at the renowned University hospitals in Heidelberg and at the Berlin Charité. Prior to his current position, Dr Oweira held a position as a consultant at the Hirslanden Surgical Centre clinics of the Hirslanden Hospitals.
Abstract:
Liver resections are performed to manage benign and malignant focal lesions in the liver and the post-operative outcome was improved over time due to improvement of surgical techniques which get benefit from understanding the liver anatomy and segmentation with improvement of hemostasis techniques. Anatomy wise liver is divided to 2 lobes (right and left) ant into 8 segments classified by Couinaud based on vascular inflow and outflow. There are many techniques for liver parenchymal transection started with clamp-crush technique and developed to ultrasonic vibration (harmonic shear), cavitron ultrasonic surgical aspirator (CUSA), hydro jet, radiofrequency dissector and recently staplers. There are numerous types of resection could be divided to major (>2 segments) and minor (<2 segments) and could be divided into anatomical (right and left hepatectomy, right anterior and posterior sectionectomy and left lateral sectionectomy), non-anatomical resection and individual segmentectomy. There are many other interventional procedures can be done during surgery for hepatic focal lesions rather than surgery as radiofrequency ablation (RFA), cryoablation or irreversible electroporation (IRE) which usually kept as combined intervention with surgery in deep parenchymal lesions which is difficult to be removed without injuring or scarifying a major hepatic structure. Also one of the elegant techniques in management of hepatic focal lesions especially malignant one is adjuvant or pre-operative angio-embolization or chemo/radio embolization which deprives the lesion from its blood supply and supplying it with chemo or radiotherapy which may decrease the size of lesion and make it easier and accessible to be removed. In addition to that, systemic chemotherapy could have benefit in malignant lesions as it may decrease the size of the lesions and minimize the liver parenchyma needed to be resected to remove the whole lesion and sometimes it changes non resectable liver lesions to resectable one.
Keynote Forum
Dr. Mostafa Yakoot
Green CRC, Egypt
Keynote: Shortened 8 weeks therapy of sofosbuvir/daclatasvir is non-inferior to 12 weeks course in chronic hepatitis C infected patients who achieved very rapid virologic response
Biography:
Consultant physician and medical director at Green CRC, Alexandre, Egypt.
Abstract:
BACKGROUND
The most recent European Association for the Study of the Liver (EASL) 2016 Guidelines on treatment of hepatitis C (HCV), allowed for shortening the course of treatment for some subsets of patients with sofosbuvir/ledipasvir based on cutoff baseline HCV RNA values. We assumed that it would be prudent to consider an objectively assuring very rapid, on-treatment, virologic response to therapy at week 2 (vRVR) before taking the decision of shortening the treatment duration. So we planned this study to test whether a dual sofosbuvir/daclatasvir (SOF/DCV) treatment duration tailored according to achieving vRVR to 8 or 12 weeks is non-inferior to the recommended fixed 12 weeks course in non-cirrhotic Egyptian chronic HCV genotype-4 patients.
METHODS
The study was conducted in an outpatient setting according to a prospective, randomized, open-label, comparative, non-inferiority study design. A hundred twenty eligible, non-cirrhotic, chronic HCV patients were randomly assigned (1:1) to receive daily doses in the form of one Gratisovir 400 mg table (generic sofosbuvir produced by Pharco Pharmaceuticals, Alexandria, Egypt) plus one Daktavira 60 mg tablet (generic daclatasvir produced by Dawood Pharm, Egypt) for either a fixed 12 weeks duration (reference group) or a response tailored duration (test group). In the test group the treatment duration was tailored according to the virus load tested by real time PCR into 8 weeks for patients who had undetectable HCV RNA level in their serum by the end of the second week of treatment (vRVR)), or 12 weeks for those who did not show vRVR. The primary outcome of the trial was the proportions of patients achieving SVR12 (HCV RNA below lower level of quantification at week 12 after end of treatment). The comparison between groups was based on testing the null hypothesis of inferiority of the response-tailored group with a pre-specified margin of non-inferiority (NI-m) of 0.1 (10%).
RESULTS
Starting from Jun, 5 2016, a hundred twenty eligible patients from 4 outpatient clinics in Alexandria, Egypt were randomized to either a fixed duration group (reference group: n = 60 patients) or a response tailored duration group (test group: n = 60 patients). During the whole period of the study, only 1 patient dropped-out from each group. Both were lost to follow-up after the 4th week's visit. Baseline characteristics in both groups were almost matching. Fifty eight out of the total 60 intention-to-treat (ITT) patients in the reference group achieved SVR12 (96.67% (95% confidence interval (CI): 88.64–99%). Whereas, 59 out of the total 60 (ITT) patients in the test group achieved SVR12 (98.33% (CI: 91.14–99.71%). The per-protocol (PP) analysis, excluding patients who dropped-out before collecting their final result, showed that 58/59 (98.31% (CI: 91–99.7%)) of patients in the reference group and 59/59 (100% (CI: 93.89–100%) of the test group achieved SVR12. Non-inferiority was declared since the upper bound of the two-sided 95% CI for the difference in proportions of SVR12 between groups (P(reference) − P(test)) did not exceed the specified non-inferiority margin of +0.1 (10%), both in ITT population (−1.67%, CI: −9.8%–+5.9%), and in the PP population (−1.69%, CI: −9%–+4.58%). No fatalities or serious adverse events were reported during the period of the study. Similar rates of non-serious adverse events were reported in both groups with a trend of higher incidence rate in the fixed 12 weeks group; all were mild in severity.
CONCLUSIONS
Shortening the duration of therapy based on observed vRVR could provide a prudent basis to avoid unnecessary long treatment courses. This could not only reduce the drug exposure and the risk of adverse drug reactions, but also cut the cost of full treatment course with such expensive medications by one third. This could economize the treatment budget at the individual out-of-pocket level as well as the public health services and insurance levels and allow for better utilization of public health resources.
- Liver and Biliary
Location: Hyatt Regency Osaka
Session Introduction
Omer Engin
Associate Professor of General Surgery. Health Sciences University, Tepecik Training and Research Hospital, Surgery Department, Izmir, Turkey
Title: Management of liver trauma: Case reports and literature review
Biography:
Omer Engin MD,
Associate Professor of General Surgery. Health Sciences University, Tepecik Training and Research Hospital, Surgery Department, Izmir, Turkey
Abstract:
A lot of surgeons may not do liver resection for malignancy in their surgical practice but they may have to operate liver because of traumatic injuries of liver. Such operations can be changed from simple suturing to resection. So, all of the surgeons must know liver anatomy and surgical operation techniques.
Liver injuries may occur after blunt or penetrating injuries. Clinical presentation may change from silent symptoms to shock symptoms. There are two liver injuries cases are presented except for another all of our liver injuries cases.
Some imaging modalities can be used that ultrasonography, CT, MRI as a noninvasive. Diagnostic peritoneal lavage and laparoscopy can be chosen such as invasive techniques.
Treatment of this lacerations can be divided into medical and surgical. Parenteral replacement of liquid, erythrocyte, thrombocyte and fresh frozen plasma are in the medical treatment options of the liver lacerations. Surgical management of the liver varies from patient to patient.
Abdel Rahman A Al Manasra
Jordan University of Science and Technology, Jordan
Title: Associate Professor of General Surgery. Health Sciences University, Tepecik Training and Research Hospital, Surgery Department, Izmir, Turkey
Biography:
Jordan University of Science and Technology, Jordan
Abstract:
Introduction & Aim: Fungal organisms can be found in biliary cultures of patients on prolonged antibiotics treatment and have stents; however, fungal masses, or balls, are rarely encountered and extremely difficult to eradicate. The aim of this study is to share our experience in fungal cholangitis complicating malignant bile duct obstruction and to reviews reports previously published concerning management of the recurrent obstruction secondary to Candida infections and its correlation with biliary malignancies.
Methods: We present our experience with 3 patients who complained of obstructive jaundice. All patients had multiple episodes of fungal cholangitis. Bile samples were obtained during percutaneous trans-hepatic cholangiogram (PTC). Two patients were diagnosed with cholangiocarcinoma and one with adenocarcinoma of the head of the pancreas.
Results: Persistent biliary candidiasis may carry a higher morbidity when it rises on the background of biliary malignancy, due to the prolonged course of medical treatment and patient hospitalization, recurrent obstruction with fungus balls, frequent needs to intervene with invasive procedures such as ERCP and PTC and the delay in initiation of chemotherapy.
Conclusion: Patients with positive fungal cultures of bile samples obtained by PTC may have coincidental cancers; similar to cholangiocarcinoma, peri-ampullary tumors and gallbladder cancer, therefore, screening with tumor markers, cytology samples and imaging studies is recommended. Aggressive sensitivity-based treatment with systemic antifungals along with external biliary drainage and irrigation with anti-fungals may be necessary for eradication of infection.
- Liver Diseases
Session Introduction
Jong Won Kim
Chonbuk National University, South Korea
Title: Inhibition of glutathione peroxidase-4 alleviates non-alcoholic steatohepatitis by suppressing lipid peroxidation in mice
Biography:
Jong-Won Kim is a Ph, D at the Chonbuk National University where he researches pathogenesis of several non-infectious diseases including acute or chronic hepatitis. He holds a B.S. degree in molecular biology and a Doctor of Veterinary pathology from the same university. He has his expertise and tries to clarify the mechanism of non-infectious diseases and contributes to the development of new therapeutic strategies.
Abstract:
Reactive oxygen species (ROS) plays a key role in non-alcoholic steatohepatitis (NASH). Inactivation of glutathione peroxidase-4 (GPX4) induces ferroptosis, which is an iron dependent and lipid peroxidation-mediated non-apoptotic form of cell death. The aim of this study was to investigate the impact of GPX4 on the progression of NASH at an early stage. C57BL6/J mice were fed a methionine and choline-deficient (MCD) diet for 10 days to induce NASH. To determine the role of GPX4 on NASH progression, the inhibitor (RSL-3) and the activator (sodium selenite) of GPX4, the inhibitor of ferroptosis (Liproxstatin-1, Lip-1) and an iron chelator (deferoxamine mesylate salt, DFO) were used in current experiments. RSL-3 treatment showed decreased hepatic expression of GPX4, 12/15-lipoxygenase and apoptosis inducing factor, indicating that GPX4 plays, a key role in NASH-related lipid peroxidation and its-associated cell death. Consistently, serum biochemical analysis showed increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in MCD-fed mice with RSL-3 treatment. In line with these results, NASH-related hepatic steatosis, inflammation and apoptosis were also increased in MCD-fed mice with RSL-3 treatment. However, sodium selenite treatment showed an opposite and protective effect on NASH progression in MCD-fed mice. Administration of DFO showed significantly lowered NASH severity and abolished the harmful effects of RSL-3-mediated GPX4 inhibition in MCD-fed mice. Finally, Lip-1 treatment showed repressed hepatic lipid peroxidation and its associated cell death resulting in decreased NASH severity. Consistent with in vivo findings, similar results were observed in palmitic acid-induced in vitro NASH condition. Taken together, we conclude that ferroptosis might play a major role in development of NASH. These results suggest that modulation of iron-mediated ferroptotic cell death might pave the way for a new strategy in treating NASH.
Rays H Y Jiang
University of South Florida, USA
Title: Using single cell omics to decode liver heterogeneity in development and cancers
Biography:
Rays H Y Jiang takes on a pioneer role in establishing a viable research program of genomics in University of South Florida, USA. She has published in high profile journals such as Cell, Science, Nature Communications and Genome Research and secured diverse funding sources from NIH, NSF and Gates’ foundations.
Abstract:
The human liver is the largest internal organ that performs over 500 physiological functions. We used single cell omics to study thousands of primary hepatocytes from human donors with healthy and pathological livers. We also developed specialized computational methods to decode single hepatocyte spatial and temporal information in livers. Our single cell RNAseq analysis revealed enormous transcriptional and biochemical heterogeneity within a single donor liver. We discovered that the principle of essential configuration of maximally incompatible biochemical pathways governs complex liver physiology in the liver lobules. We also studied hepatocyte heterogeneity at single cell level in developmental and cancer livers of humans. Within a hepatocyte cellular carcinoma biopsy sample, there is a continuum of oncogenic transformation degree of hepatocytes, which mirrors the embryonic liver developmental process with the exception of erythropoiesis function. The majority of the tumor derived hepatocytes show properties similar to that of healthy donors, albeit with reduced primary liver functions. Importantly, we found a small group of liver cancer stem cell like progenitors, expressing arrays of embryonic markers such as SOX4, HMGA1 and CXCR1, indicating enhanced onco-genic proliferation potential. Our single cell omics study revealed important temporal and spatial heterogeneity related to liver functions and oncogenic-transformation in humans.
Zhuo Wang
Southern University of Science and Technology, China
Title: Stat3 tyrosine phosphorylation is critical for hepatocellular carcinoma proliferation, survival and angiogenesis in response to lipopolysaccharide
Biography:
Zhuo Wang is a well-qualified, highly skilled and motivated person with more than 8-year work experience in liver disease. She has completed her PhD degree from Hong Kong Polytechnic University in 2014 and currently she is working at Southern University of Science and Technology. Her research focuses on liver fibrosis and liver cancer recently these years.
Abstract:
Hepatocellular carcinoma (HCC) is a long-term sequence of chronic inflammatory liver injury and hepatic injury is associated with a defective intestinal barrier and increased hepatic exposure to bacterial products including lipopolysaccharide (LPS), which promotes hepatocarcinogenesis. Despite its clinical signiï¬cance, mediators responsible for the high risk of inflammation to develop HCC in the chronically injured liver remain to be clarified. Here, we report a novel mechanism by which LPS/signal transducer and activator of transcription 3 (STAT3) signaling promotes the angiogenesis in HCC both in vitro and in vivo. STAT3 activated by LPS increases the production of vascular endothelial growth factor (VEGF) by tumor cells, which in turn stimulates the migration and tubulogenesis of endothelial cells through STAT3 activation and hence promotes angiogenesis in HCC. Moreover, our data suggested that hypoxia-induced VEGF expression, which also contributes to angiogenesis in HCC, was in a STAT3-dependent pathway. Our findings not only provide a potential mechanism by which bacterial infection enhances HCC oncogenesis through promoting the angiogenesis in liver, but also suggest that targeting STAT3 might be an effective therapeutic strategy in HCC treatment considering the dual roles of STAT3 in angiogenesis.
Claudio Agustino
Faculty of Medicine University of Indonesia , Indonesia
Title: Comparison between Albumin, Prothrombin Time, and Fibrinogen Profile in Staging of Liver Cirrhosis based on APRI Score Classification
Biography:
Claudio A is a medical student from University Indonesia. He has won several competitions such as
Scientific Poster in Tarumanegara Medical Competition held by Tarumanegara University and
emergency medical responder held by the National Medical First Responder Team Organization.
He also active in several organization such as First Responder Team in Faculty of Medicine
University of Indonesia and Student Council Organization. As a medical student, he also made a
research and wrote Evidence Based Case Report about Hepatology and interested in that field.
Abstract:
Cirrhosis is an end stage of chronic inflammatory disease with the destruction of liver tissue and
fibrosis that impairs its function to synthesis albumin, prothrombin, and fibrinogen. Cirrhosis can be
detected and classified into 3 groups with non-invasive diagnostic technique by using APRI score.
This study aims to find out the significant difference between albumin, prothrombin time, and
fibrinogen profile within cirrhosis stages based on classification from APRI score. Design of the
study is cross sectional with 60 patients which meet the criteria from the medical records in the
Clinical Pathology Laboratory and center of medical record of RSCM.: The results of the study
were analyzed with Kolmogorov Smirnov test showed albumin level, prothrombin time, and
fibrinogen (median 2.91, 11.8, and mean 273.7117) , Anova or Kruskal Wallis test showed
significant difference between these three components based on score APRI classification. ( all
p<0.05).Then, Post hoc test (Bonferroni for Anova, Mann Whitney for Kruskal Wallis) of
albumin’s profile showed significant difference for comparison between group APRI score less than
0.5 and more than 2. Post hoc test of prothrombin time showed significant difference from all
comparisons. Post hoc test of fibrinogen profile showed significant difference from comparison
between group APRI less than 0.5 and more than 2 ; APRI less 0.5 – 2 and more than 2. As a
results, there are significant difference from comparison between albumin, prothrombin time, and
fibrinogen profile in staging of liver cirrhosis based on classification from APRI score.