World Hepatitis Day: Interview with Fabien Zoulim and Focus on Julie Lucifora’s Research
On the occasion of World Hepatitis Day, Fabien Zoulim, Professor of Medicine at University of Lyon, head of the Hepatology Department of Hospices Civils de Lyon, head of the Inserm Viral Hepatitis Research Unit (U1052), coordinator of the European project IP-cure-B, the university hospital research project CirB-RNA and the ANRS HBV Cure Task Force, presents the key takeaways from the ANRS HBV Cure 2022 workshop.
• Advances in the understanding of HBV persistence mechanisms
Recent data on the viral reservoir (HBV cccDNA) were presented at this edition of the HBV Cure workshop. The researchers discussed how this reservoir is formed and regulated during chronic infection and how it could be targeted, particularly through new "genetic scissors" approaches.
The researchers also presented recent data on the immunological mechanisms involved in patient immune response defects in order to better understand and effectively restore them and thus enable control or elimination of the virus, particularly through new approaches such as therapeutic vaccines.
• New technologies for evaluating the infection site (hepatic compartment), viral reservoir, and hepatic immune response
Virological and immune evaluation of the hepatic reservoir is important as it will determine the impact of the new therapeutic approaches that are currently being evaluated in clinical trials on the viral reservoir and the antiviral immune responses.
The experts discussed new approaches to analyzing the hepatic compartment, less invasive than liver biopsy, such as fine needle aspiration. New PCR and immunology technologies would also make it possible to study the viral reservoir and intrahepatic immune responses on this type of specimen in clinical trials, thereby generating information crucial to the development of novel therapeutic approaches.
• Overview of the therapeutic advances in hepatitis B and HBV-HDV co-infections
A review of the most recent clinical trials was carried out, showing that this field of research is very dynamic. Numerous antiviral molecules and several immunotherapy strategies are in the phase II clinical trial stage, most often in the form of combination therapy: either with direct antivirals or with direct antivirals plus immunotherapy.
Major advances have been made on certain classes of molecules, such as capsid inhibitors and strategies targeting viral RNA (with siRNA or antisense nucleotides).
Regarding hepatitis Delta, a virus entry inhibitor (bulevirtide) has received conditional approval by the European Medicines Agency (EMA) – given that so far no treatment has been available for this form of hepatitis. The modes of administration are being developed pending the results of the phase III clinical trials. Other antiviral molecules are also being studied in various clinical trials.
In therapeutic research on hepatitis B and Delta, ANRS | Emerging Infectious Diseases is sponsoring and funding the cohort study BuléDelta (follow-up of patients on bulevirtide) which has already recruited 193 patients in 30 centers. It is also sponsoring IP-cure-B, a clinical trial funded by Europe that aims to stimulate antiviral immune responses with a TLR8 agonist (selgantolimod) and has already recruited six patients in France.
Next on the HBV and HDV research meeting agenda: the International HBV Meeting
The next International HBV Meeting will take place in Paris, France, from September 18 to 22, 2022. It will bring together researchers studying the biology of the hepatitis B and Delta viruses and its co-organizers are David Durantel (Inserm) and Hélène Strick-Marchand (Institut Pasteur).
Julie Lucifora is an Inserm researcher working at the International Center for Research on Infectious Diseases (CIRI) in Lyon (Inserm, CNRS, ENS de Lyon, Lyon 1 University) within the HepVir laboratory led by David Durantel. She is also a board member of AC42, the group overseeing fundamental research on viral hepatitis within the agency. As part of World Hepatitis Day, we met with her to find out more about her research.
I developed a passion for virology early on in my studies; then I did an internship in Fabien Zoulim’s team which was working on hepatitis and which led me to make it the focus of my career.
In HepVir, we are working on hepatitis viruses in order to further our understanding of how they interact with their host cells and to identify new therapeutic targets for testing new molecules and developing new antivirals.
In recent years, I have mainly worked on the interaction between the hepatitis B (HBV) and Delta (HDV) viruses. HDV is a satellite of HBV and co-infection with these two viruses can induce one of the most aggressive forms of chronic viral hepatitis with an increased risk of and faster progression to cirrhosis or cancer of the liver. The precise reasons for the worsening of liver disease are poorly understood. Although HDV needs HBV in order to spread throughout the body and from one individual to another, it was noted that in most HBV/HDV co-infected patients, HBV viral loads are lower than in HBV mono-infected patients. To improve the medical treatment of these co-infections, it is important to better understand the modes of interaction between the two viruses and the cells of the liver. My work is about understanding, from a molecular point of view, the mechanisms that lead to HBV inhibition by HDV. We hope that this will allow us to better understand the worsening of HBV-induced liver disease by HDV and to develop new treatments for patients.
In my opinion, two major challenges remain to be addressed. The first being the necessity to find strategies to eliminate HBV and HDV, and the second being the need to find a vaccine for the hepatitis C virus because, although a treatment exists, it remains relatively costly and therefore not always accessible.
Links to the rest of the kit produced as part of World Hepatitis Day 2022:
- Focus on ICONE, a project to reduce hepatitis C among drug users: https://www.anrs.fr/en/actualites/1123/world-hepatitis-day-focus-icone-project
- Focus on TA-PROHM, a project to limit mother-child transmission of the hepatitis B virus in Cambodia: https://www.anrs.fr/en/actualites/1126/world-hepatitis-day-focus-ta-prohm-project
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