Virtual ICE-HBV Workshop On Serum Biomarkers Session 2
ICE-HBV is organizing an virtual and interactive workshop on HBV biomarkers endorsed by the International HBV Meeting. The event is aimed at scientists, clinicians, pharmaceutical and diagnostic industry representatives. The workshop, chaired by Anna Kramvis and Peter Revill, is put together by the ICE-HBV serum biomarkers working group. Both classic and future biomarkers will be discussed. The workshop will lead to a consensus statement on promising serum biomarkers.
The workshop will be divided in two sessions, held on Monday Oct 5 and Monday Oct 12, 2020, via Zoom. Both sessions will start at 12PM GMT, go for approximately 2.5 hours each, and will be recorded. More information here.
Free registration is open here.
October 12th - 140 Minutes Total - Time in GMT
Session Co-Chairs: Christian Bréchot & Ourania M. Andrisani
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Christian Bréchot, MD, PhD joined the USF Health Morsani College of Medicine part time as Senior Associate Dean for Research in Global Affairs, Associate Vice President for International Partnerships and Innovation, and Professor in the Division of Infectious Disease, Department of Internal Medicine Since 2017, Dr. Brechot has served as President of the Global Virus Network, a network of 48 research centers worldwide, headquartered in Baltimore.
Before serving as president of the Pasteur Institute from 2013 to 2017, Dr. Bréchot was vice president of medical and scientific affairs at Institut-Merieux, a company that develops new approaches to fight infectious diseases and cancers. He also served as the general director of Inserm, the French national agency for biomedical research from 2002 to 2007. As professor of hepatology and cell biology at Necker School of Medicine, Paris Descartes University, he led the clinical department of liver diseases at Necker-Enfants Maldes Hospital from 1997 to 2001.
Authoring more than 400 articles in medical and scientific journals, Dr. Bréchot was ranked by the Institute for Scientific Information as the 4th most cited author on the topic of hepatitis C. He has been recognized as an inventor on 18 patents, and helped create three biotechnology companies: Rarecells, ALFACT Innovation, and The Healthy Aging Company.
Dr. Bréchot’s research activities have focused on viral hepatitis: hepatitis B (HBV) and C (HCV), particularly with regard to their role in liver cancer (Hepatocellular carcinoma: HCC) and to the molecular mechanisms that drive liver regeneration and cancer (in particular, cell cycle deregulation and the impact of oxidative stress). He has been the member of numerous scientific committees and societies and has received prestigious awards.
Ourania Andrisani, Ph.D., Distinguished Professor of Basic Medical Sciences, Purdue University, Program Leader, Purdue Center for Cancer Research. Ourania Andrisani is a molecular biologist with research interests and expertise on molecular mechanisms of transcriptional regulation, epigenetics, and signal transduction involved in cell growth control, cellular differentiation and cancer pathogenesis. Her laboratory studies epigenetic mechanisms involved both in Hepatitis B virus (HBV) biosynthesis and virus-mediated hepatocarcinogenesis. Her laboratory aims to identify essential mechanisms that can be targeted to suppress both HBV infection and HBV-mediated liver cancer. She is Program Leader for the Purdue Center of Cancer Research (2018-present), co-organizer of the International Conference on the Molecular Biology of Hepatitis B viruses for 2020/21, and has been actively involved in graduate education and training. She has served as permanent member of the Endocrinology (NIDDK) and the Molecular Oncogenesis (NCI) study sections, and continues to serve as reviewer of other NIH study sections, international funding agencies, and high impact journals.
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Noon Housekeeping Rules Capucine Penicaud 12:00-12:10pm
Welcome by Peter Revill & Fabien Zoulim – ICE-HBV Chairmanship Handover.
Introduction of Session Chairs Christian Bréchot and Ouriana M. Andrisani.
Biomarkers of HBV cccDNA expression + Q&As
See AbstractTitle: Biomarkers of HBV cccDNA expression Date of presentation: October 12th, 2020 Authors: Maura Dandri Affiliation: Research Group Viral Hepatitis, Center for Internal Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany Abstract Body: Chronic hepatitis B virus infection cannot be completed eliminated due to the persistence of the covalently closed circular (cccDNA), the template of HBV transcription in infected hepatocytes. Since assessment of cccDNA amounts and activity requires an invasive procedure, there is an urgent need for serum biomarkers that can accurately correlate with cccDNA expression in the liver. Different types of HBV serum biomarkers have been proposed, which include classical markers, such as HBsAg, and newer markers such as HBV RNA and core related antigen. However, their function, events that may affect their production and clinical relevance in chronic HBV infection is not fully understood. This presentation will focus on the cccDNA as producer of HBV serological biomarkers, giving emphasis on how distinct therapeutic approaches may affect the levels of virological markers, in particularly HBV RNA in serum, and to which extent such changes can provide information about the amounts and activity of intrahepatic cccDNA. Current gaps of knowledge, caveats and open questions will be discussed.
See BioMaura Dandri is full Professor at the University Medical Center Hamburg-Eppendorf, where she leads the research group Viral Hepatitis. She received her B.S. in Natural Science and PhD in Microbiology and Immunology at the University of Trieste, Italy; was Post-doctoral Fellow at Albert Einstein College of Medicine, New York, and at Heinrich-Pette-Institute, Hamburg, Germany (EMBO Fellowship). The German Research Foundation awarded her with a Heisenberg Professorship. Her research focuses on developing infection models to study interactions between hepatitis viruses, human hepatocytes and immune cells. She also investigates the potential of HBV/HDV therapeutic strategies using humanized mice and patient sample analyses.
Biomarkers of Occult HBV infection + Q&As
See AbstractTitle: Biomarkers of Occult HBV infection Date of presentation: Oct 12, 2020 Authors: Teresa Pollicino Affiliation: University Hospital of Messina, Italy Abstract Body: Occult HBV infection (OBI) is defined as the presence of replication-competent HBV DNA (cccDNA) in the liver and/or HBV DNA in the blood of people who test negative for HBsAg. Intrahepatic HBV DNA is the gold standard diagnostic biomarker for OBI. However, liver tissue is not always available, and there is no standardized assay. A more common (but less sensitive) approach to diagnose OBI is the detection of HBV DNA in the blood. Because serum HBV DNA is usually present in low concentrations and may only be intermittently detected in OBI, analyzing serially collected blood samples, and testing DNA extracts from no less than 1 ml of serum/plasma is recommended for OBI diagnosis. Anti-HBc may be used as a surrogate marker to identify OBI in blood/organ donors and people who will receive immunosuppressive therapies. However, the absence of anti-HBc does not rule out OBI.
See BioTeresa Pollicino MD is a Professor of Molecular Medicine and Pathophysiology and Head of the Molecular Hepatology Laboratory of the Division of Clinical and Molecular Hepatology, University Hospital of Messina, Italy. In 1990, she received her MD in Medicine and Surgery at the of Messina, where she completed her residency in Hematology and Internal Medicine. Dr. Pollicino has worked in numerous international research centers including: 1996-1998, “Unité de Recombinaison et Expression Génétique”, Institut Pasteur, Paris, France 2002-2003, Laboratory of Gene Expression, Regina Elena Institute, Rome 2015-2016, Hepatic Pathogenesis section, Laboratory of Infectious Diseases, NIH, Bethesda, MA, US.
Biomarkers of liver cancer +Q&As
Title: Biomarkers of Liver Cancer
Date of presentation: October 12, 2020
Author: Patrizia Farci, MD
Affiliation: Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, NIH
HCC is the seventh most common human cancer and the second leading cause of cancer-related death globally. HBV is the leading cause of HCC worldwide. The prognosis of HCC is poor and, as a result, the incidence and mortality rates are roughly equivalent. The complexity of HCC is rarely seen in other cancers, and the lack of early diagnostics and effective treatments has made this cancer one of the most challenging. Patients with cirrhosis are at highest risk for developing HCC. The current surveillance strategies in high-risk populations using ultrasound imaging with or without serum alpha-fetoprotein (AFP) are suboptimal for the early detection of HCC, which is critical for a better prognosis. Although a series of HCC biomarkers are under clinical evaluation, including novel biomarkers derived from Omic technologies, their clinical validation is still in the early phases. Only AFP has completed the 5 phases required for routine clinical use, but there are limitations with its sensitivity and specificity. In my presentation, I will discuss the current state of HCC surveillance, the present challenges, and the areas of future research.
Patrizia Farci, M.D.
Chief Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, NIH
Patrizia Farci earned her M.D. at the University of Cagliari Medical School, Italy, and then became a board-certified specialist in Infectious Diseases and in Gastroenterology at the same University. She did her postdoctoral training at the Molinette Hospital in Turin under Dr. Mario Rizzetto and at the Royal Free Hospital School of Medicine in London under Prof. Sheila Sherlock. In 1989, she joined the laboratory of Dr. Robert H. Purcell at the NIH as a Visiting Scientist. In 1992, she became Associate Professor of Medicine and, in 2000, Full Professor of Medicine and Director of the Liver Unit at the University of Cagliari, Italy. In 2007, she returned to the NIH, where in 2010 she become the Chief of Hepatic Pathogenesis Section in the LID, NIAID.
Point of Care Testing - an unmet and urgent need + Q&As
See AbstractTitle: Point of Care Testing- an unmet and urgent need Date of presentation: October 12, 2020 Authors: Daryl Lau, MD, MPH Affiliation: Harvard Medical School Abstract Body: Current access to HBV care is suboptimal in the resources limited settings. The inaccessibility of diagnostic tests poses an obstacle for effective HBV screening and treatment programs. There is an urgent need for reliable and affordable point-of-care (POC) tests that can be applied to provide the best quality of care within available resources. A comprehensive and practical HBV management guidance applying such POC tests to meet the acceptable health standards and prepare the health systems to adapt to the evolving hepatitis B treatment advances is essential in the resources limited settings.
See BioDaryl Lau, MD, MPH is an associate professor of medicine in Harvard Medical School. Her major research interest has been the clinical and translational investigation of liver disease and in particularly viral hepatitis. She has conducted studies on the natural history, therapeutic trials and new diagnostic assays on hepatitis B, hepatitis C and delta hepatitis. Currently, she serves as the program director of the NIH sponsored Harvard hepatitis B Consortium to advance the diagnosis, understanding of the pathogenesis and treatment of chronic hepatitis B and its complications.
Bench to Bed: Relevance of biomarkers used in in vitro and in vivo model systems to the clinic + QAs
See BioInstitute of Medical Virology, Justus Liebig University Giessen, National Reference Centre for Hepatitis B Viruses and Hepatitis D viruses Head: Prof. Dieter Glebe, PhD.
Major Research Interest: The overall aim of his research is focused on understanding the evolutionary background and molecular mechanism involved in infectivity, persistence and neutralization of hepatitis B and D viruses. In the past, he discovered and characterized a new species of hepatitis delta-like viruses and various hepadnaviruses from mammals, including hepadnaviruses from primates, bats and shrews that could serve as animal models for HBV and HDV. He is also interested in HBV vaccines and analysed efficiency of neutralising antibodies against HBV surface proteins. During the last years, D. Glebe has devoted substantial parts of his research to the understanding of processes that constitute current genetic diversity, infectivity and pathogenicity of hepatitis B viruses, hepatitis D viruses and related animal viruses.
Panel Co-Chairs: Fabien Zoulim and Mala Maini
See Panel Chair BiosFabien Zoulim obtained his M.D. in Gastroenterology and Hepatology in Lyon Medical School in 1991. He has also obtained a PhD in Molecular and Cellular Biology and was trained as a post-doctoral researcher at Fox Chase Cancer Center in Philadelphia. He is Professor of Medicine at Lyon I University since 1997. He is currently Medical Director of the Hepatology Department at the Hospices Civils de Lyon, and Scientific Director of the Department of Immunology and Virology of INSERM Unit 1052 where he is leading the team on ‘Antiviral therapy of viral hepatitis’. Dr Zoulim has served as an Associate Editor for Journal of Hepatology and is currently Associate Editor for Gut. He also served as an expert in the microbiology study section of the INSERM and is currently head of the clinical viral hepatitis study section at ANRS. He served as a Governing Board member of the European Association for the Study of the Liver (EASL). Dr Zoulim received the William Prusoff award of the International Society for Antiviral Research. Furthermore, he has been the scientific coordinator of a European community-funded Network of Excellence on the management of antiviral drug resistance, and is currently head of the ANRS “HBV cure” program in France. Fabien Zoulim is a recognised expert in the field of viral hepatitis and antiviral therapy. He has published more than 350 articles (H index 63, Web of Science).
Mala Maini is a Professor of Viral Immunology in the Division of Infection and Immunity at UCL, London and also works as a Consultant Physician in the viral hepatitis clinic. Her lab researches liver immunity and immunopathology, focusing on cellular interactions and metabolic constraints. By dissecting the immune correlates of viral persistence and liver damage, the Maini lab aims to contribute to the development of novel immunotherapeutic strategies for hepatitis B and hepatocellular carcinoma. Their work is funded by the Wellcome Trust, Cancer Research UK, Medical Research Foundation, NIHR, EU, UKRI, British Infection Association.
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1:30-2:20pm Industry Panel Discussion: What are the most clinically relevant biomarkers?
Participants: Gavin Cloherty, Jenny Yang, Oliver Lenz, Bill Delaney and Henry Chan
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Gavin A. Cloherty, Ph.D., is head of Infectious Disease Research for Abbott’s diagnostics business. He provides scientific leadership in the area of infectious disease diagnostics by conducting groundbreaking clinical studies on hepatitis and HIV and developing new tests. As one of the top experts in the field, his innovative research is changing the way infectious diseases are being diagnosed to help improve patient outcomes.
Gavin has more than 20 years of experience with Abbott and leads a team of scientists in the study of the viral diversity of HIV and hepatitis. His expertise is sought after globally through his established partnerships with commercial organizations, ministries of health, government agencies and academic institutions, such as the Centers for Disease Control and Prevention (CDC) and National Institutes of Health’s AIDS Clinical Trial Group (ACTG) and Hepatitis B Research Network (HBRN). He has worked with the Republic of Georgia to help eradicate hepatitis C in the country, and is looking to expand these efforts to other regions of the world severely impacted by this disease.
Jenny Yang, PharmD is a Senior Director of Clinical Research at Gilead Sciences. After working on the global development and registration of Gilead’s HCV marketed products including Sovaldi®, Harvoni®, and Vosevi®, she now leads the HBV Cure clinical development program at Gilead. Prior to her 13-year experience in drug development at Gilead and Novartis, she completed her PharmD at the University at Buffalo, School of Pharmacy and Pharmaceutical Sciences.
Oliver Lenz, PhD is Scientific Director Clinical Microbiology and Immunology at Janssen Infectious Diseases, part of the Janssen Pharmaceutical Companies of Johnson & Johnson. He is the global virology lead for the development of HBV therapeutics from pre-clinical through clinical development. Prior to his work in HBV he was involved in the discovery of the HCV protease inhibitor simeprevir which he supported subsequently through clinical development until registration. Oliver Lenz completed his PhD at the University of Marburg, Germany, mainly working on hemorrhagic fever viruses and did a postdoctoral fellowship at the European Molecular Biology Laboratory (EMBL) at Grenoble, France, on HIV GP41 structural biology. He is author of 70 peer reviewed papers and co-chair of the HBV Forum surrogate endpoints working group.
William Delaney, PhD joined Assembly Biosciences as Chief Scientific Officer, Virology in May 2020. Prior to joining Assembly, he most served as Executive Director, Biology at Gilead. During his 20-year career at the Gilead, he headed the Viral Hepatitis & Herpes Discovery Biology Groups and served as the Research Therapeutic Area Head for HBV. He began his career as a Research Scientist, Clinical Virology at Gilead and later transitioned into Drug Discovery where he held positions of increasing responsibility. Over the course of his career, he has contributed to the development of several marketed products, including Hepsera®, Viread®, and Vemlidy® for HBV and Sovaldi®, Harvoni®, Epclusa®, and Vosevi® for HCV. He earned a BS in Biotechnology from the University of Delaware and a PhD in Cell and Molecular Biology from the Penn State College of Medicine. In addition, he was a Postdoctoral Fellow at the Victorian Infectious Diseases Reference Laboratory (VIDRL), Department of Research & Molecular Development.
Professor Henry Lik Yuen Chan is Professor of Medicine and Associate Dean (External Affairs) of Faculty of Medicine, The Chinese University of Hong Kong. He is a world-renowned expert in viral hepatitis B, and is chairman of the Strategic Technical Advisory Committee on Viral Hepatitis for the Western Pacific Regional Office of World Health Organization. He has published over 450 papers in peer-reviewed journals, and is awarded Highly Cited Researcher by Clarivate Analytics in 2018 and 2019 for producing multiple top 1% cited papers under Web of Science.
2:20-2:30pm Concluding remarks and next steps Anna Kramvis