Day :
- Genetic and Metabolic Liver Diseases
Liver Disease Diagnosis
Liver Cancer
Non-Viral Hepatitis
Drug discovery for treatment of Hepatitis
Location: Salon II III
Session Introduction
Remy Andre-Jean
Perpignan Hospital, France
Title: Hepatitis mobile team: A new concept for benefit toward drugs users and precarious people with hepatitis C in France
Time : 11:45-12:15
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: Although highest European screening rate is in France, 44% of patients are not aware of hepatitis C because they were not diagnosed. Drug injection was main contamination route of hepatitis C virus (HCV) in France and Western Europe since 1990. French guidelines were to treat all inmates and drug users, even fibrosis level. Access of HCV screening, care and treatment in drugs users, prisoners and homeless was low in France, less than 20% and 33% of HCV patients were under diagnosed. They were considered as difficult to treat populations. All these patients need support especially psycho-educative interventions. Hepatitis Mobile Team (HMT) was created in July 2013 to increase screening care and treatment of hepatitis B and C patients. We proposed 15 services: 1. Screening by Dried Blood Spot (DBS) HIV HBV HCV 2. Mobile Fibroscan in different sites 3. Social screening and diagnosis (EPICES score) 4. Outreach center with specific health care workers 5 days/7 5. Free blood tests in primary care if no social insurance 6. Advanced on-site specialist consultation 7. Access to obligatory pre-treatment commissions. 8. Individual psycho-educative sessions 9. Collective educative workshops 10. Staff training 11. Drug users prevention 12. Peer to peer program 13.Low cost specific patients mobile phones 14.Specific one day hospitalizations before and after antiviral treatment 15. Green thread: outside DBS and FIBROSCAN* in specific converted truck.
Objective: Increase screening care treatment access and cure for target population.
Patients & Methods: Target population was drugs users, prisoners, homeless, precarious people, migrants and psychiatric patients. We proposed part or all of our services to our medical and social partners. They choose only services what they need.
Results: From 2013 July to 2015 December, we did 2056 DBS for 1485 people (944 HCV DBS). Our HCV active file was 244 patients, 18% of new patients screened by DBS; 83% realized all blood tests and FibroScan; 59% need treatment according to French recommendations; 50% started treatment and 49% have been cured. Quality of program for patient were free access, closeness (outside hospital), speed (of the results) and availability (of nurse and social workers).
Conclusions: Specific screening, follow up and support of these difficult to treat populations are essential for increase medical management and cure of HCV patients. HMT offered complement services and not substitution of existing services. It was new useful tool to screen, diagnose and treat these patients by outside pathway of care. French Health Ministry announces treatment for all HCV patients in June 2016 and HMT was a cost efficient program to treat every patient.
Fragomeli V
Nepean Hospital, Australia
Title: Treating patients with hepatitis C genotype 1 using Viekira Pakâ„¢ in the real world: An Australian nursing perspective
Time : 12:15-12:45
Biography:
Vince Fragomeli is a Clinical Nurse Consultant at Department of Gastroenterology and Hepatology in Nepean Hospital, Australia.
Abstract:
Introduction: Viekira Pak™ (paritaprevir/ritonavir/ombitasvir, dasabuvir) +/- ribavirin was provided to patients with hepatitis C genotype 1 via a Special Access Scheme (SAS) in Australia prior to Pharmaceutical Benefit Scheme listing. Published data demonstrated good safety and efficacy in clinical trials with SVR (sustained virological response) rates above 90%.
Aim: The aim of this nurse-led study is to assess the efficacy and safety of Viekira Pak™ in a “real world” clinical setting and to gain insight into nursing perspectives as Australia progresses towards an interferon free era. To the authors’ best knowledge, this is the first study of its kind examining SVR rates in the “real world” from a nursing perspective.
Methods: Data was collected from 140 patients across eight Australian Liver Clinics. Baseline characteristics, pathology results, adherence, compliance, treatment outcomes and adverse events were recorded and analyzed using an approved data collection template.
Results: Mean age 56 years, mean weight 84.4 kg, 65.0% male, 95.0% Caucasian, 2.9% Indigenous Australian, 2.1% Asian. 64.3% had genotype 1a, 50.7% treatment naive, 18.6% prior null-response, 77.9% had cirrhosis. Sustained virological response (SVR12) rate 95.0% (n=133). 6 patients did not achieve an SVR12 due to virological failure (n=1), relapse (n=1), lost to follow-up (n=1) premature discontinuation (n=4). 126 (90.0%) patients reported adverse events, mainly mild to moderate fatigue, nausea and headache. Bilirubin elevation was observed in 47.9% of patients; grade 4 in 3 patients (2.1%). Serious adverse events in 19 (13.6%) participants, hyperbilirubinemia (n=8), decompensation (n=2) and anemia (n=1), resulting in hospitalization, no deaths reported. One potential drug-drug interaction was identified resulting in lithium toxicity. Patients were predominantly reviewed by nurses with an average (mean) of 5.1 clinic visits from week 1 to week 12 post treatment. 85.0% of patients attended all scheduled visits. 85.0% of patients reported 100% adherence to medication.
Conclusion: This “real world” analysis of Viekira Pak™ demonstrated high SVR rates similar to those achieved in clinical trials. Participants reported excellent treatment adherence, compliance and tolerability of Viekira Pak™. Reported adverse events were mainly mild to moderate intensity and serious adverse events were rare. The potential for drug-drug interactions (DDI’s) highlight the need for adequate monitoring of patients whilst on treatment. This study supports the implementation and utilization of a nursing model of care to treat patients with chronic HCV in the Direct Acting Antiviral (DAA) era. The implementation of a nursing model of care has a far reaching impact in the global ability to reduce the worldwide burden of HCV by facilitating the rapid and safe treatment uptake for HCV patients undergoing HCV therapy.
Eman El-Ahwany
Theodor Bilharz Research Institute, Egypt
Title: New insights into the roadmap of pathogenesis of liver fibrosis
Time : 12:45-13:15
Biography:
Eman El-Ahwany is a Professor of Immunology, Immunology and Drug Evaluation Department, Theodor Bilharz Research Institute (TBRI), Egypt. She was graduated from Faculty of Science, Cairo University in 1991. She has received her PhD in Immunology in 2001 and worked as a Teaching Assistant and Faculty part-time in the Biology Department, the American University in Cairo (1999-2014). She is a Member in the TBRI technical office and the TBRI Internal Research Projects Committee since 2011. She is a Member in the European Association of Liver Diseases (EASL). Her field of interest is miRNAs and the epigenetic changes as non-invasive diagnostic and therapeutic tools in HCV-induced liver fibrosis and HCC. She has shared and worked as participant, Co-PI and PI in 20 research projects sponsored by international and national agencies, published 35 research articles in peer reviewed international journals, presented several abstracts in 30 international conferences and supervised 15 MSc and PhD theses. She has been awarded the TBRI excellence award in 2014. She is the Coordinator of MOU between TBRI and Basque University in Spain (2016). She has received Post doctorate Fellowships in Germany (2007) and France (2014).
Abstract:
Liver fibrosis is a wound healing scar response following acute and chronic liver diseases including chronic hepatitis B and C, autoimmune hepatitis, non-alcoholic steatohepatitis and alcoholic liver disease. The patho-histological findings of liver cirrhosis, the end-stage of liver fibrosis, show hepatocellular death, a lobular inflammatory cell infiltrate, excessive deposition of ECM proteins, and the appearance of regenerative nodules that may result in liver failure, portal hypertension and hepatocellular carcinoma. The pathophysiology of liver injury has attracted the interest of experimentalists and clinicians over many centuries. With the discovery of liver-HSC, the insight into the cellular and molecular pathobiology of liver fibrosis has evolved and the pivotal role of HSC as a precursor cell-type for ECM-producing myofibroblasts has been established. Although activation and trans-differentiation of HSC to myofibroblasts (MFs) is still regarded as the pathogenetic key mechanism of fibrogenesis, recent studies point to a prominent heterogeneity of the origin of myofibroblasts. The newly discovered pathways supplement the concept of HSC activation to MFs, point to fibrosis as a systemic response involving extrahepatic organs (lung and kidney) and reactions and offer innovative approaches for the development of non-invasive biomarkers and anti-fibrotic agents.
Makki H Fayadh
Advanced Center for Day Care Surgery, UAE
Title: 40 years observation in liver diseases in the Middle East
Time : 14:45-15:15
Biography:
Makki Hummadi Fayadh is a senior consultant Physician & Gastroenterologist- Hepatologist & Endoscopist both in Iraq & UAE . He was graduated from the Medical College University of Baghdad and completed his Post graduate studies in Medicine & Gastroenterology in UK-London. Became a member of MRCP UK and worked in Saint Bartholomew’s hospital in London in the Gastroenterology department with Sir A.M.Dawson, during that time trained in endoscopic techniques and did research on malabsorption especially celiac disease, colitis, bile stone dissolution inflammatory bowel diseases & gastrointestinal lymphomas. He joined
in Advanced Center for Day care surgery-ACDS as a consultant physician gastroenterologist & Medical director.
Abstract:
Gastrointestinal and liver diseases are major causes of death and disability in Middle East and North Africa. Diarrheal diseases have been replaced by gastrointestinal cancers and cirrhosis in most countries in the region. In the Gulf GCC countries, Jordan & Iraq, GIT cancers are increasing. Gastrointestinal and liver diseases show variability in the pattern of their prevalence, incidence, mortality and the final burden they impose. Some countries such as Afghanistan and Pakistan are still facing gastrointestinal infectious diseases; other countries with better economy in the region have experienced the obvious transition from communicable to non-communicable diseases. Liver cirrhosis is among the top four causes of death in all countries in our area. The death rate caused by cirrhosis in Egypt is by far the highest in the world, followed by Pakistan, Afghanistan, Yemen and Morocco. Pakistan is specifically experiencing an epidemic of cirrhosis. Liver cancer is among the top four causes of death in 18 countries. In Iraq chronic liver diseases are very prevalent and account for 2/3rd of the admissions, the important causes is in the following order, hepatitis B, alcohol, hepatitis C, immune hepatitis and metabolic diseases. The prevalence of non-alcoholic fatty liver disease is rapidly increasing and non-alcoholic steatohepatitis has become a leading indication for liver transplantation. Diarrheal diseases have been replaced by gastrointestinal cancers and cirrhosis in most countries in the region. In the Gulf GCC countries, Jordan & Iraq cancers are increasing. Chronic hepatitis B and C are the main causes of liver cirrhosis and progression to hepatocellular carcinoma. Gastrointestinal and liver diseases show variability in the pattern of their prevalence, incidence, mortality and the final burden they impose. There is marked difference in prevalence of liver disease in our area. Diarrheal diseases have been replaced by gastrointestinal cancers and cirrhosis in most countries in the region. Liver cirrhosis is among the top four causes of death in all countries in our area.
Biography:
Osama Hasan Othman has completed his MBChB in Mosul Medical College in 1980, gained DM, CABM Baghdad in 1992, MRCP1in1988 and FRCP London in 2012. He is currently a Chief of Department of Medicine, previously Sub-Dean of Scientific Affairs in Medical College. He shares in most of scientific activities in the college and Azadi Teaching Hospital and has published many papers and editorials.
Abstract:
Hepatitis itself is not a genetic disease. Hepatitis B virus got genetic diversity. HBV is DNA virus which replicates by RNA intermediate as its DNA polymerase has reverse-transcriptase RT. The mutation rate for HBV is high. HVB classified on base of genomic sequencing, antigenic subtypes of glycoprotein surface antigen HBsAg. Genotype-subtype has geographical distribution related to population movement and significant events. Mutation and mutant selection occurred among all HBV variants. They have relevant medical and public health implications. Pre-core (pre-C) defective variant has less susceptibility to Interferon with high failure rate to other antiviral drugs related to selection of resistant variants mutation in genome encoding viral RT activity. As RT overlaps HBsAg molecule code, selection of drug resistant variants indirectly leads to selection of HBsAg variants commonly encountered in chronic HBV carriers. The significance of this emerges under the pressure of neutralizing antibody response leading to resistance to both vaccination and immunotherapy noted often among liver transplant recipients and babies born to HBV-carrier. HBsAg variants also associated with false negative results in diagnosis of new infections, detection of chronic carriers, screening for blood donation and manufacture of therapeutic blood products.
Ali Mahzari
RMIT University, Australia
Title: Matrine eliminates hepatosteatosis and glucose intolerance in high fructose-fed mice by suppressing ER stress associated de novo lipogenesis in the liver
Time : 15:45-16:15
Biography:
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.
Abstract:
Matrine is a small molecule (MW: 248) isolated from a natural product and used as a prescribed hepatoprotective drug in humans with little adverse effect. Our recent work shows that matrine can reduce glucose intolerance in mice caused by excess lipid intake directly from diet. Here, we investigated whether matrine may also be efficacious for hepatosteatosis and glucose intolerance due to hepatic de novo lipogenesis from high carbohydrate. This study was performed in high fructose-fed mice for 8 weeks with matrine treatment (100 mg/kg/d) administered in the last 2 weeks. We found that matrine markedly reduced hepatosteatosis (100% reduction in triglyceride content, p<0.01 vs. untreated group) and glucose intolerance (ACU: HFru+HuM1 vs. untreated, P<0.05) without affecting caloric intake. Fructose-induced increases in SREBP1c (by 66%) and SCD1 (by 72%) in the hepatic lipogenic pathway were all suppressed by the treatment with matrine (all p<0.05). As our earlier work revealed ER stress as a mechanism of fructose-induced de novo lipogenesis, we examined hepatic ER stress following matrine treatment. Indeed, matrine significantly decreased IRE1 by 2 fold (p<0.01 vs. untreated group) in the ER stress pathway. These results together suggest that matrine eliminates hepatosteatosis and glucose intolerance by suppressing ER stress associated lipogenesis in the liver. To further assess the implications of these findings to the glycaemic control for diabetes, we generated a type-2 diabetes model in mice by high fat feeding (to produce insulin resistance) plus low doses of streptozotocin (to decrease plasma insulin by 50%). Consistent with the effects in high fructose-fed mice, matrine reduced hepatic triglyceride content (by 60%) and SREBP1c level (by 57%, p<0.05) in the liver and significantly lowered the hyperglycaemia. Collectively, our findings indicate that the hepatoprotective drug matrine may be repurposed for the treatment of hepatosteatosis and type-2 diabetes associated de novo lipogenesis in the liver.
Biography:
Salem Awadh is a Consultant Gastroenterologist at Advanced Center for Day Care Surgery LLC, UAE. He has published numerous research papers and articles in reputed journals and has various other achievements in the related studies. He has extended his valuable service towards the scientific community with his extensive research work.
Abstract:
UAE was a country of intermediate prevalence and now it is considered a low prevalence because of the policy of universal vaccination since 1992. The complete, sustained clearance of HBV among chronically infected patients, and the hope of eradicating HBV from our planet should be our dream and mission in the coming years. H BsAg have served as a qualitative serological marker of HBV infection for several decades. Since 2004, due to development of advanced quantitative assays for HBsAg level has led to much interest in its potential use to monitoring the status of chronic HBV infection and antiviral response. Baseline HBsAg level and its dynamic characteristics during therapy with nucleoside/tide analogues or interferon{ INF} have become very important predictors of antiviral response. HBsAg titres are not associated with ALT levels among most patients in the same phase. Genotypes are the most important determinants of HBsAg levels both for treatment-naïve and treated patients. Genotype A seems to have a higher probability of HBsAg loss in both the natural course of HBV infection and antiviral treatment. 10% of patients of affected patients have genotype A in UAE and the predominant genotype is genotype D which is difficult to treat and 25% seroconvert ion fron e antigen positive to e antigen negative after one year Serum HBsAg levels tend to be higher in; HBeAg positive, Genotype A. Special mutations of HBV S gene can lead to HBsAg variants which may be under estimated or undetectable by current assays. Clinicians should therefore pay attention to false loss of HBsAg for some patients with HBV s Ag variants. Achievement of HBsAg seroconversion does not always indicate HBV eradication during PEG-INFa therapy. Coinfection or superinfection of HBV with HCV, HDV, HAV, or HEV may lead to lower levels of HBsAg and HBV DNA than single HBV infection in the same natural phase. Different antiviral treatment protocols have different effects on HBsAg decline and HBsAg is highest in immunotolerant phase. “HBsAg level < 1500 IU/ml at week 12 of PEG-INFa therapy had a PPV of 33% for HBeAg seroconversion 24 weeks after EOT”. at week 24 HBsAg level : <300 IU/ml is SVR Predictor HBsAg loss is reached in 3-7% of patients. Patients with HBsAg titres > 20 000 IU/ml at weeks 12, 24 of PEG-INF-a were considered not to have achieved a post-treatment response , this could be used as a “stopping rule. PEG-INF-a -Patients with HBsAg < 1500 IU/ml at week 12 of PEG-INF attained an HBsAg clearance rate of 17.6% at 24 weeks after EOT. PEG-INF-a -In patients with : HBsAg Decline >1 log 10, and serum level < 300 IU/ml at 24 weeks during treatment achieved a SVR rate of 75% compared with only 15% those who did not have these criteria. PEG-INF-a -On treatment: HbsAg levels <1,500 IU/ml at 12 week,s could predict SVR 12 months after EOT. After HBeAg loss, serum HBsAg decline seems to somewhat underestimate the decline of cccDNA, and the decline of serum HBV DNA is much greater than the reduction of intrahepatic viral load.
- Dear Hepatitis 2016 attendees!
We would like to inform you that 3rd Day of the conference i.e., (October 12th, 2016) is scheduled for Business to Business Meeting, Networking with Keynotes, speakers, moderator and lunch will be provided from 12:00 -13:30.
We are very much glad to anticipate your presentation at networking and lunch session on 3rd day of the conference.
Thanks and Regards,
Joseph Raven
Hepatitis 2016
- Workshop
Location: Salon II III
Session Introduction
Nermeen Nabil Ashoush
The British University in Egypt, Egypt
Title: Economic evaluation of direct acting antivirals therapy in chronic hepatitis C
Biography:
Nermeen Nabil Ashoush has completed her PhD in 2015 from Ain Shams University in the field of Clinical Pharmacy and Pharmacy Practice. Also, in 2015 she has completed a Diploma in Health Economics and Outcome Research from the University of Washington. She is working as a Lecturer in Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, The British University in Egypt. She is also the Head of the Health Economics Unit, Center for Drug Research and Development, The British University in Egypt.
Abstract:
Hepatitis C is a chronic health problem affecting approximately 180 million people worldwide. Chronic hepatitis C is one of the main causes of end-stage liver disease and hepatocellular carcinoma that have a clinical and economic burden on hepatitis C virus (HCV) patients.
Over the past few years, new medicines for HCV infection have begun to transform the treatment landscape; the development of new regimens involving direct acting antivirals (DAAs) have been so successful that disease experts are heralding an era where all HCV patients of all genotypes can be cured, even debating whether eradication is possible.
These novel agents seem to facilitate the use of shortened courses of combination interferon-free therapy, which are associated with high (>95%) sustained response rates and relatively few toxicities. These regimens have also been successful in patients who were previously difficult to treat, including those with cirrhosis. The main drawback of these new agents is the huge price tag, which will make treatment out of reach for people in the developed and developing world. Understanding the balance between costs and efficacy is critical to making decisions about the optimal use of these new agents, especially for health-care systems constrained by rising costs. Our goal for this workshop is to facilitate an understanding of the importance of health economics and pharmacoeconomics evaluations in guiding policy decisions about the use of newly approved drugs as well as future therapies.
- Workshop
Location: Salon II III
Session Introduction
Bouchkira Hakim
Centre Hospitalier de Perpignan, France
Title: Increase of specific social score EPICES before and after direct antiviral agent treatment in HCV patients in France: Two years experience
Biography:
Hakim Bouchkira is a Nurse Coordinator of Mobile Hepatitis Team at Centre Hospitalier de Perpignan, France. He is working in Perpignan Hospital since 2006.
Abstract:
Introduction: Hepatitis C was most frequent in vulnerable people who were insecure and had multiple viral risk factors. Vulnerable people included inmates, migrants, drug users, homeless and psychiatric patients. Accessibility of health system was not so easy, most part for these populations because of social, psychiatric and addictive issues. In May 2014, French national experts rapport reported about connections between social vulnerability and hepatitis B and C incidence. That is was why vulnerable populations were particularly affected by HCV and HBV infections. Validated tools to evaluate this phenomenon were not sufficiently put to use social inequalities of healthcare must be taken in account in fight against HBV and HCV. This report recommended evaluating first social vulnerability situation, proposing best support and taking in account these factors with medical and social workers. Hepatitis Mobile Team (HMT) was created in July 2013 to increase screening care and treatment of hepatitis B and C patients. We proposed 15 services: Screening by Dried Blood Spot (DBS) HIV HBV HCV, Mobile Fibroscan* in different sites, social screening and diagnosis (EPICES score), outreach center with specific health care workers 5 days, free blood tests in primary care if no social insurance, advanced on-site specialist consultation, access to obligatory pre-treatment commissions, individual psycho-educative sessions, collective educative workshops, staff training, drug users prevention, peer to peer program, low cost specific patients mobile phones, specific one day hospitalizations before and after antiviral treatment and Green thread: outside DBS and FIBROSCAN* in specific converted truck.
Objective: Evaluation of modification of specific social score before and after direct antiviral agent HCV treatment in vulnerable people.
Methodology: We used specific social score called EPICES (evaluation of individuals’ factors affecting vulnerability in health exams centers) two times for every patient, in first contact and 3 months after treatment. EPICES score (14 questions) was created in 2004 and was demonstrated specific action to detect and quantify precarious people. EPICES score was positive for precarious situation at 48.5 value and maximum score was 100. All patients with value above 48 saw social worker for social evaluation.
Preliminary Results: HMT used EPICES score since September 2014 for all new HCV patients. In 2015, 36 EPICES scores were realized before AAD treatment with average value at 77. In 2016, 64 scores EPICES were realized before DAA treatment with average score at 70 and average post treatment value at 52. Difference between pre and post treatment values were significant (p<0.05).
Conclusion: Hepatitis Mobile Team was an innovative concept that promotes return of known HCV patients and new diagnosis patients in circuit of care by facilitating access to screening and FIBROSCAN* but also for social worker and hepatologist consultation. Training and coaching people with precarious situation, investment and adherence to project of our partners, increase number HCV patients supported treated and cured.
- Hepatitis Care and Cure
Hepatitis B
Hepatitis C
Hepatitis Vaccination
Liver Diseases
Location: Salon II III
Session Introduction
Arnolfo Petruzziello
IRCCS, Italy
Title: Hepatitis C Virus (HCV) genotype 1b as a risk factor for hepatocellular carcinoma development in chronic HCV positive patients in Southern Italy
Time : 12:00-12:30
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
Fatma Abdelaziz Amer
Zagazig University, Egypt
Title: Direct acting antivirals; are they truely the last nails in the coffin of HCV ??
Time : 12:30-13:00
Biography:
Fatma Abdelaziz Amer has worked as the Head of Medical Microbiology and Immunology and is currently a Supervisor of the Infection Control Program, Zagazig Faculty of Medicine, Egypt. She has obtained her MSc degree in Infection Control and is the President of the Arab Alliance for the Prudent use of Antimicrobials and the Hepatitis Working Group, International Society for Chemotherapy. She has published more than 35 papers in national and international journals. She has developed two parts of infection control books. She has attended more than 50 conferences all over the world and has been aiding as a Reviewer, Editorial Board Member and Co-Editor in many national and international journals.
Abstract:
Nearly, 170 million people worldwide are suffering from chronic HCV infection. The introduction of the direct acting antivirals (DAAs) for the treatment has revolutionized the management of this major health problem. In addition to the currently available DAAs agents, recent drugs in the anti-HCV pipeline have enhanced capacity, as well as improved tolerance and safety profiles. High rates of sustained virologic response (SVR) are produced by DAAs in clinical trials (90%- 95%); nevertheless, treatment failure in real-life cohorts sometimes occurs. Treatment failure may present with null- response, breakthrough, partial response or relapse. In a given host, HCV population is a heterogeneous mixture of closely related genomes composed of the wild type plus other strains present at lower frequencies (HCV quasipecies). Under selective pressure of exposure to DAAs certain genetic variants which are normally present before start of treatment, can proliferate and become the dominant variant leading to treatment failure. These resistance associated mutations depend on the class of DAAs used and also vary between HCV genotypes and subtypes.
Breakthrough mutations have already been reported for NS3/4A protease inhibitors (O80K, V36AM, T54A/S, R1556K/T, A156S/T, D168N), for NS5A inhibitors (M28, Q30, L31V, Y93H), and for NS5B inhibitors (S282T, V321l, L159F). Emerging mutants can be detected by genotypic assays; population sequencing, clonal analysis and ultradeep sequencing. Phenotypic assays can also be used for the determination of drug susceptibility and cross-resistance profile / replicon system.
All efforts should be directed towards optimizing anti-HCV regimens to maximize SVR and minimize resistance.
Andrew Vaillant
Replicor Inc., Canada
Title: Nucleic acid polymers: Application in the treatment of chronic HBV and HBV/HDV infection and potentiating the effects of immunotherapy
Time : 13:45-14:15
Biography:
Andrew Vaillant is the inventor of Replicor’s NAP technology and has more than 15 years of experience in viral biology, antiviral drug development and nucleic acid chemistry. He has authored numerous publications and patents on the development and use of NAPs as agents to treat infectious diseases. He previously held positions at two Montreal-area biotechnology companies. He was a Postdoctoral Fellow at the Montreal Neurological Institute and holds a PhD in Cell Biology from the University of Ottawa, Canada.
Abstract:
Nucleic acid polymers (NAPs) have the unique ability to block the release of the hepatitis B surface antigen (HBsAg) from infected hepatocytes and clear HBsAg from the blood of human patients, a critical step in achieving a functional cure in HBV and HBV/HDV infection. Recent data will be presented from the ongoing REP 301 clincal trial (NCT02233075) which is assessing the safety and efficacy of the NAP REP 2139 when used in combination with pegylated interferon alpha 2a in patients with chronic HBV/HDV co-infection. These clinical data demonstrate the unique ability of NAPs to clear circulating HBsAg and HDV in patients. Clearance of HBsAg is accompanied by important immunological impacts: The appearance of anti-HBs, a synergistic improvement in the effiacy of pegylated interferon and the ability to achieve complete control of HBV and HDV infection with a finite course of treatment.
Ligita Jancoriene
Vilnius University Hospital Santariskiu Klinikos, Lithuania
Title: Direct-acting antivirals Ombitasvir/Paritaprevir/Ritonavir+Dasabuvir with or without Ribavirin in HCV genotype 1-infected treatment-naive or treatment-experienced patients with or without cirrhosis
Time : 14:15-14:45
Biography:
Ligita Jancoriene was graduated from Vilnius University Medical Faculty in 1989 and completed her Residency in Gastroenterology (1993). During her PhD studies she received Clinical Training in Infectious Diseases at Karolinska Institutet, Huddinge University Hospital, Sweden (1999-2003) and defended PhD thesis in a field of Infectious Diseases and Hepatology on the Management of Chronic Viral Hepatitis C (2003). She is working at the Department of Infectious diseases of Vilnius University since 1997 and also working as a Specialist of Infectious diseases and Gastroenterology at the Centre of Infectious diseases in the Vilnius University Hospital Santarisiu Klinikos since 1996. Currently, she is a Professor at the Department of Infectious, Chest diseases, Dermatovenerology and Allergology of Vilnius University and Head of the Department for Consultation and Immunoprophylaxis at the Centre of Infectious diseases in the Vilnius University Hospital Santariškių Klinikos. She is a Member of the European Association of the Study of the Liver and International Society of Travel Medicine. She is a Board Member of the Lithuanian Society of Infectious Diseases and Baltic Immunoprophylaxis Association. She is a co-author of scientific papers in peer-reviewed journals on vaccination and treatment of chronic viral hepatitis C. She was a Principal Investigator in more than 20 clinical trials on viral hepatitis and influenza treatment and vaccination.
Abstract:
The aim of multicenter, international, real-life study was to evaluate efficacy and safety of Ombitasvir/Paritaprevir/Ritonavir+Dasabuvir±Ribavirin in treatment-naive and treatment-experienced GT1-infected patients, who failed previous PEG-INF/RBV±first generation protease inhibitor therapy. 114 (54 males) GT1-infected (102-GT1b) patients, aged 54.4±10.6 years, were included. 28.1% were treatment-naive, 71.9% treatment-experienced. 21 patients failed previous triple therapy with telaprevir or boceprevir. 57% were cirrhotics. Treatment was scheduled for 12 weeks in 112, 24 weeks in 2 patients. RBV was administered to 89 patients. Sustained virologic response (SVR12) was assessed by HCV-RNA undetectability 12 weeks after the end of treatment (EOT). 111 patients completed therapy and had undetectable HCV-RNA at the EOT. 73 patients with available follow-up evaluation achieved SVR12. The average reduction in alpha-fetoprotein (16.3 versus 4.9, p<0.001) and hepatic fibrosis (17.3 versus 15.5, p<0.001) was demonstrated at the end of follow-up. RBV was reduced in 18, discontinued in 11 patients. The most frequent adverse events were asthenia (25.4%), fatigue (15.8%), itching (13.2%) and dyspepsia (11.4%). Treatment was disontinued in 3 patients due to exacerbation of psoriasis (day 3), depression (week 5) and elevation of ALT, AST (week 9). 10 liver transplant patients recieved 24 weeks treatment(4 males, 50.7±8.0 years, 9-GT1b, 8-treatment-experienced). RBV was administred to 9, reduced in 3, discontinued in 2 patients. All patients completed therapy and had undetectable HCV-RNR at the EOT. 9 patients with available follow-up evaluation achieved SVR12. In conclusion, treatment with Ombitasvir/Paritaprevir/Ritonavir+Dasabuvir±Ribavirin achieved 100% SVR12. Adverse events were mostly mild and related to RBV administration.
Asad Izziddin Dajani
Arab Doctors Specialist, UAE
Title: Current therapeutic approaches to NAFLD treatment
Time : 14:45-15:15
Biography:
Asad Izziddin Dajani has obtained his Medical degree Cum Laude from Cairo University. He pursued his Postgraduate studies in Internal Medicine in UK and Austria. He has 32 years’ experience at hospitals in Egypt, Kuwait, Austria and UAE, gaining wide experience in his field. In 1984, he relocated to UAE, where he was instrumental in establishing endoscopy service at Kuwait and Al Qassimi Hospitals in Sharjah. He regularly attends and participates in local, regional and international conferences. He is regularly invited as a guest lecturer to medical conventions, institutes and pharmaceutical events. He has many publications to his credit in reputed local and international journals.
Abstract:
Nonalcoholic fatty liver disease (NAFLD) is the commonest liver disease; its prevalence had increased over the past 10 years. The treatment of NAFLD is of prime concern due to the mortality and morbidity it implies and that standard of care medications remain experimental. Treatment is focused on lifestyle modification and managing the comorbid diseases with a possible role for hepatic protective agents. Weight reduction by dietary control, physical exercise, orlistat or surgery is a pivotal step in treating NAFLD. Insulin sensitizers: Metformin and pioglitazone were used alone or in combinations with other remedies to treat NAFLD. Pioglitazone induced a convincing effect; however relapse was common which raised concern about complications. DPP-IV inhibitors and GLP-1 agonists reduced Hepatocyte Steatosis and improved hepatocyte survival. Reduction of blood lipids: Statins and Ezetimibe have good effect when used for NASH with dyslipidemia. Antioxidants: Vitamin-E, alone and with vitamin-C, EPL, sylimarin and metformin revealed limited effects. A metanalysis demonstrated that high dose vitamin-E increased all cause mortality. Pentoxiphylline targeting fibrosis showed antioxidant and antifibrotic effects. UDCA had inconsistent results and was not recommended for the treatment of NAFLD/NASH. Probiotics research had shown encouraging results and indicated that they could be an emerging therapeutic option. Investigational medicines like obeticholic acid, ARBs, elafibranor (GFT 505), and simtuzumab are being evaluated; some of them seem to be promising. Medicines in pipeline preclinical studies revealed good results with DUR-928, GR-MD-02, Aramchol, RG-125 and Cenicriviroc. A decade of clinical trials did not reveal an intervention that improved all outcomes for NASH but research indicates promising prospects.
Prapan Jutavijittum
Chiang Mai University, Thailand
Title: Hepatitis B revaccination to students whom firstly demonstrated anti-HBs negative or titer <10 mIU/ml
Time : 15:15-15:45
Biography:
Prapan Jutavijittum has obtained Board of General Pathology (Anatomic and Clinical Pathology) certificate in Thailand in 1990. He is currently an Assocate Professor at Department of Pathology, Faculty of Medicine, Chiang Mai University, Thailand. He has published more than 20 papers in reputed journals.
Abstract:
In 2013, first year medical students and nurse students of Chiang Mai University were tested for the presence of HBsAg and quantitative levels of anti-HBs. The students whom tested negative for HBsAg and anti-HBs negative or titer <10.0 mIU/ml were called back for 3-dose course of hepatitis B (HB) revaccination. Blood samples were taken at 8-10 months after the 1st dose of HB revaccination. Of 408 subjects, 3 (0.7%) were HBsAg-positive and 332 (81.4%) were anti-HBs negative or titer <10 mIU/ml and 76 (18.6%) were anti-HBs titer ≥10 mIU/ml. 2/248 (0.8%) of the students were test positive for anti-HBc. Among persons who born short after adoption of universal neonatal HB immunization in Thailand; at least 0.8% were infected and recovered from HBV infection, 0.7% became HBsAg carriers and at age 17-19 year-old 81.4% were anti-HBs negative or titer <10 mIU/ml. The young adults whom firstly demonstrated anti-HBs negative or titer <10 mIU/ml required at least 2-dose course of HB vaccination to achieve protective levels of anti-HBs. Among the complete 3-dose course of HB revaccinated subjects, only 5/236 (2.1%) have failure to raise anti-HBs ≥10 mIU/ml. Our data support the need of pre-booster check and HB revaccination to whom received neonatal HB vaccination if long time after that they have opportunities for HBV exposure, e.g., joining healthcare disciplines.
Nermeen Nabil Ashoush
The British University in Egypt, Egypt
Title: Therapeutic trial to assess the efficacy and safety of folic acid and/or vitamin B complex on hepatitis C infected patients treated with pegylated interferon and ribavirin
Time : 16:05-16:35
Biography:
Nermeen Nabil Ashoush has completed her PhD in 2015 from Ain Shams University in the field of Clinical Pharmacy and Pharmacy Practice. Also, in 2015 she finished a Diploma in Health Economics and Outcome Research from the University of Washington. She is working as a Lecturer in Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, The British University in Egypt. She is also the Head of the Health Economics Unit, Center for Drug Research and Development, The British University in Egypt.
Abstract:
Background & Aims: Pegylated-interferon α-2a and ribavirin (PIFN/RBV), the current standard treatment for hepatitis C virus (HCV) infection in Egypt is frequently associated with hematological adverse effects, leading to high treatment discontinuation rates. The objective of the present study is to explore the effectiveness of intervening with folic acid (F) and/or vitamin B complex (B) compared with placebo (C) in HCV treatment Egyptian patients for the management of treatment induced deterioration of health related quality of life (HRQOL) as well as hematological parameter. Methods: In a randomized controlled trial, one hundred and sixty subjects were randomly assigned to receive PIFN/RBV in addition to BF, B, F or C. Blood samples were collected at different time points during 48 weeks and at 12 and 24 weeks post treatment for complete blood count and for HCV RNA real time PCR. Short form SF 36V2 questionnaire were used to assess HRQOL at various time during and post treatment. Results: Egyptian HCV patients treated with PIFN/RBV showed deterioration of HRQOL which were correlated with deterioration in the measured hematological parameter. Supplementation with vitamin B complex plus folic acid significantly (P<0.001) decreased the deterioration observed in physical and mental health as well as complete blood count. Supplementation with either vitamin B complex or folic acid were also effective but with lower potency than their combination. Conclusion: BF supplementation can reduce adverse effects of PIFN/RBV therapy in chronic hepatitis C patients, which may improve patients’ HRQOL and their adherence to combination antiviral therapy.
Mahmoud Fahmi Elsebai
Mansoura University, Egypt
Title: Potent and broad spectrum medicinal drugs against all genotypes of hepatitis C virus (HCV)
Time : 16:35-17:05
Biography:
Dr Mahmoud Elsebai has completed his PhD in 2011 from Bonn University (Germany) and postdoctoral studies from Oulu Uni (Finland) and Nice Uni (France). He has published more than 20 publications (including patent applicaations) in reputed journals such as J Virology, Med Chem Letters, European J Org Chem and Nat Prod Reports. He is working on chasing hepatitis c virus using ntural compounds and recently in 2016 he has discovered potent and broad spectrum compounds against HCV which published in J Virology. He is a reviewer in many international journals.
Abstract:
As many as 200 million people worldwide are infected with hepatitis C virus (HCV). About 3-4 million people are infected per year and more than 350,000 people die yearly from hepatitis C-related diseases. In the present study, the water extract of the leaves of the wild Egyptian artichoke (WEA) showed improvement of HCV infection symptoms. Therefore, our study was divided into two main strategies: The clinical investigation of WEA extract on some infected Egyptian patients. The results showed outstanding activity against HCV and its complications such as ascites and jaundice by measuring the PCR and liver functions such as ALT and AST. The phytochemistry of the WEA extract and its subsequent evaluation of inhibition capacity in vitro using cell-culture derived HCV: The chemical investigation of the WEA extract resulted in the identification of six compounds. Importantly, all compounds inhibited HCV infection; compounds cynaropicrin and grosheimol were the most potent among the six. The EC50 were estimated at 1.03 μM, 1.27 μM and 299 μM for compounds 1, 2 and WEA extract, respectively, by using a luciferase-carrying reporter virus. Time-of-addition experiments revealed that they inhibit HCV virus at a time-point during entry. Furthermore, compounds 1 and 2, apart from cell-free infection inhibited HCV cell-cell transmission. Finally, the results showed that compounds 1 and 2 inhibited HCV particles from genotypes 1a, 1b, 2b, 3a, 4a, 5a, 6a and 7a indicating that these compounds inhibit HCV cell entry independently of viral genotype or subtype. Thus, these compounds are promising candidates for the development of new pangenotypic entry inhibitors for the HCV infection. All of these results were applied for patenting.
Eman El-Ahwany
Theodor Bilharz Research Institute, Egypt
Title: Circulating microRNAs as non-invasive biomarkers for the detection of different stages of liver fibrosis in Egyptian HCV patients
Biography:
Eman El-Ahwany (PhD) is a Professor of Immunology, Immunology and Drug Evaluation Department, Theodor Bilharz Research Institute (TBRI). She was graduated from Faculty of Science, Cairo University in 1991. She has received her PhD in Immunology in 2001. She has worked as Teaching Assistant and Faculty (part-time) in the Biology Department, the American University in Cairo (1999-2014). She is a Member in the TBRI Technical Office and the TBRI Internal Research Projects Committee since 2011. She is a Member in the European Association of Liver Diseases (EASL). Her field of interest is miRNAs and the epigenetic changes as non-invasive diagnostic and therapeutic tools in HCV-induced liver fibrosis and HCC. She has shared and worked as participant, Co-PI and PI in 20 research projects sponsored by international and national agencies, published 35 research articles in peer reviewed international journals, presented several abstracts in 30 international conferences and supervised 15 MSc and PhD thesis. She has been awarded the TBRI excellence award in 2014. She is the Coordinator of MOU between TBRI and Basque University in Spain (2016). She has obtained Post doctorate fellowships in Germany (2007) and France (2014). She has been awarded the TBRI excellence award in 2014.
Abstract:
Background: In liver fibrosis, miRNAs play an essential role in activating HSCs proliferation, differentiation and migration. To study regulation of genes at the miRNA level is a huge advantage as gene expression, is regulated at an epigenetic level before even proteins get formed. Aim: The aim of the study is to develop a non-invasive diagnostic tool based on measuring the serum levels of different miRNAs in order to detect HCV-induced liver fibrosis at the early stages of the disease. Patients & Methods: Subjects of the current study included 66 cases of chronic hepatitis C (CHC) with early stage of fibrosis, 65 cases of CHC with stage 4 of fibrosis admitted to department of hepato-gastroenterology, TBRI. 35 subjects were included as normal controls. Five main miRNAs (miR-214, miR-221/222, miR-9, miR-125b and miR-128) were measured using real-time reverse transcription-polymerase chain reaction. Results: Circulating levels of miR-214, miR-221/222, miR-9, miR-125b and miR-128 were significantly increased (P<0.01) in cases of both CHC with early stage of fibrosis and CHC with stage 4 compared to control group. Also, there was a significant increase (p<0.01) in CHC with stage 4 of fibrosis group versus CHC with early fibrosis group. Conclusions: Our data suggest that circulating miRNAs could serve as novel biomarkers for the detection and assessment of liver fibrosis.
Muhammed Alaa Hammad
Mansoura University, Egypt
Title: Exploring victims of needle stick injuries among health-workers in Mansoura University Hospitals and assessing the knowledge of medical students of Mansoura Faculty of Medicine for the different types of hepatitis (A, B & C) those are common in Egypt
Biography:
Muhammed Alaa Hammad is currently working as an eminent faculty member at Mansoura University, Egypt. He has extended his valuable service towards the scientific community with his extensive research work.
Abstract:
Background: Hepatitis A, B and C have been encroaching into Egypt's cities in the recent years. Thus, appropriate preventive measures should be taken into consideration. Objective: Clinical level-Knowing all health-workers who have been struck by needle stick injury in the year 2015 in Mansoura University Hospitals and whether they received proper vaccination for Hepatitis B: 140 health-workers were involved. Later, a general awareness talk is done to ensure they are updated on management of possible hepatitis B affliction. Academic level: Awareness has been done to medical students and healthcare workers on 3 major hepatitis in Egypt A, B and C with a total of 903 surveyors. Methods: Clinical level: A survey is given to a health-worker where we ensure confidentiality if struck by a needle and then we aware them of hepatitis B. Academic Level: A pre-survey is given to a medical student/health worker assessing his/her knowledge of hepatitis A, B and C. A general talk targeting certain basic info needed to be known by students and clinicians is then given. A post survey is then given to assess the talk and if it added any of the target's knowledge. Results: 53% of 140 health-workers got injured by a needle stick in the past 12 months only. 68% injured due to individual carelessness besides 81% did not file incident report. Out of 140, 90 were not vaccinated for Hepatitis B and 96% did not receive training in prevention or treatment of needle stick injury. Out of 903 surveyors for general info on Hepatitis 40% answered all questions right in the pre-survey and 90% answered them right on the post-survey. Conclusions: More focus is needed to be put on informing health-workers and medical students on how to prevent needle stick injury and they in general need to be aware of the common types of hepatitis.
- Video Presentation
Location: Salon II III
Session Introduction
Gerard E Mullin
Johns Hopkins Hospital, USA
Title: Vitamin D status predicts outcome of chronic liver disease
Biography:
Gerard E Mullin is a board-certified Internist, Gastroenterologist and Nutritionist. He is an Associate Professor of Medicine and Director of Integrative GI Nutrition Services at The Johns Hopkins Hospital. He is as an authority in nutrition and gastroenterology. He teaches medical professionals at international conferences on the role of nutrition and lifestyle and the gut microbiome in digestive health outcomes. He is the author of several professional desk references and trade books including The Gastrointestinal and Liver Disease Desk Reference.
Abstract:
Vitamin D and its role in immunity, inflammation and chronic disease pathogenesis has been the subject of many scientific investigations. The progression of the chronic liver disease (CLD) to cirrhosis is the result of an imbalance between the production and dissolution of the extracellular matrix. Development of liver fibrosis in the setting of chronic hepatic inflammation and injury is orchestrated by many cell types, including hepatic stellate cells (HSCs). The significance of vitamin D deficiency in CLD and cirrhosis is emerging in the literature. We systematically evaluated the literature for the relationship of vitamin D to fibrogenic liver disease by utilizing PubMed, SCOPUS, Embase, Cochrane Database, OVID and Lilacs as part of a search protocol. Low vitamin D status predicts progression of non-alcohol fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) and then to cirrhosis and appears to predict survival. Low vitamin D status contributes to resistance to anti-viral therapy for viral hepatitis with improved response rates in those having vitamin D sufficiency. This session will review the literature, the putative mechanisms for vitamin D’s apparent effect on CLD outcome and the importance of monitoring of serum 25-hydroxyvitamin D levels for prognostication and intervention.