The Forum is an annual public awareness event co-hosted by the Hepatitis B Foundation and ICE-HBV to provide a powerful conclusion to the International HBV Meeting.
Paris, Sept. 22, 2022 – The perspectives of the almost 300 million people living with hepatitis B is critical as scientists and clinicians continue working toward hepatitis B cure and elimination, which was the focus of a special session that concluded the 2022 International HBV Meeting.
The largest global meeting focused solely on the science of hepatitis B, the HBV Meeting was held this week (Sept. 18-22) in Paris. The Community Forum provided an opportunity for the researchers, physicians and others engaged with hepatitis B to understand the needs of the greater hepatitis B community. Just as important, it allowed those living with hepatitis B to learn about the disease and progress in treatment and a cure directly from the scientists who have made this their life’s work.
This year’s Community Forum focused on the European Union, where many hurdles exist in terms of health care inequality, leading to unequal access to hepatitis B screening and treatment, health disparities, stigma and lack of prioritization to eliminate hepatitis B.
Following Marinela Debu from ELPA, the European Liver Patients’ Association, organizers and partners “call for equitable access to care in the European Union, so that when the cure comes, it benefits everyone.”
The Community Forum was co-hosted by the Hepatitis B Foundation and the International Coalition to Eliminate HBV (ICE-HBV). Foundation President Chari A. Cohen, DrPH, MPH, said: “We truly believe in the concept of ‘nothing about us without us.’ Finding a functional cure for hepatitis B will only be beneficial if we address the structural challenges already faced by people living with hepatitis B.”
Fabien Zoulim, MD, PhD, chair of ICE-HBV said, “The forum has become an integral part of the annual international meeting. Inclusion of this audience is pivotal to the success of any progress, which is why the just concluded Community Forum is an essential part of the HBV meeting.”
Findings from this year’s Community Forum highlight that, while there is much progress being made towards finding therapies that could lead to functional cure for many people living with hepatitis B, there is still much work to be done to accomplish equitable care. Improved screening systems will be required to ensure an equitable access to cure.
We are proud to let you know that we are official endorsers of the Conference on Liver Disease in Africa (COLDA) 2022! This workshop will take place on 29 September – 1 October as a hybrid workshop in the Doubletree by Hilton Cape Town Upper Eastside hotel in Cape Town, South Africa.
How close are we to finding hepatitis B’s kryptonite?
VaccinesWork spoke to virologist Dr John Tavis about an approaching arsenal of therapies.
As far as viral villains go, hepatitis B virus (HBV) is among the most wanted. Claiming the lives of two people per minute, this ferocious disease has a hit rate on par with HIV/AIDS.
Seeping into the body through contact with the bodily fluids of an infected person, HBV latches onto cells in the liver, injects its DNA and hijacks the cell’s machinery to power its own replication. HBV is a silent assassin. It can hide out for decades, causing potentially life-threatening damage to the liver and spreading to new victims before any symptoms show – claiming the lives of more than 800, 000 people each year.
“It’s great we’ve got [these therapies] but it’s not where we need to be,” he says. “One class [of drugs] is hard to take, the other you need to take forever.”
HBV’s assault on the liver causes a disease called Hepatitis B (hepB). Most adults with hepB recover within one to three months after symptoms start, but when the infection persists longer than six months it’s considered chronic. As the virus attacks the liver cells, it leaves behind nasty scars called fibrosis. In up to one-third of the patients the scars become severe (cirrhosis), eventually resulting in liver failure or liver cancer. While hepB can be fatal, it is treatable, but it is also easily prevented to a degree of 95% through routine, safe, immunisation.
Upscaling vaccination, screening and treatment is the best way to keep this viral criminal at bay. New developments or scientific breakthroughs in any of these three areas is bad news for HBV, but good news for us. So, when scientists on the frontline say this deadly disease is about to meet its match, it’s great news.
Current treatment
Current HBV treatments interfere with a specific part of the viral lifecycle – stopping the virus from replicating and spreading. None of the current therapies stop viral replication completely, but they are able to slow down replication enough to reduce the risk of liver cancer and other diseases caused by HBV infection.
When no HBV DNA or proteins can be detected in the blood months after treatment stops, the patient is considered “functionally cured”, but small amounts of the virus can still lie dormant in the body. These “sleeping” viruses can still be “woken up” by medications that suppress the immune system.
There are two types of treatment. One uses nucleot(s)ide analogues: molecules that block the viral DNA from replicating inside the host cells. The other involves flooding the body with proteins called interferons, which switch on the body’s natural immune defences against the virus.
A patient receiving interferon treatment must have a dose injected each week for a year. Unfortunately, this treatment is taxing on the body, causing flu-like symptoms for days after it’s been administered, which can have crippling ramifications for work, social and family life.
Nucleot(s)ide analogue therapies are a much easier pill to swallow – literally. Taken in tablet form once a day, this treatment is preferred over interferon treatment because it has fewer side effects. However, nucleot(s)ide analogue therapy must be administered for long periods of time and is indefinite for most. This prolonged use of nucleot(s)ide analogue treatment can also lead to side effects like bone loss and kidney problems for some of the drugs.
Professor of Molecular Virology at the Saint Louis University School of Medicine, John Tavis, said only 5-10% of patients achieve a functional cure when using these treatments. This doesn’t mean the other 90% of people aren’t greatly helped by the treatments, but the extent to which the treatments reduce the presence of HBV in the body is not high enough to consider the patients functionally cured.
“It’s great we’ve got [these therapies] but it’s not where we need to be,” he says. “One class [of drugs] is hard to take, the other you need to take forever.”
Dr John Tavis
The future of treatment
Chairman of the Scientific Advisory Council for the annual International Hepatitis B Virus Meeting and the Incoming Chair of the International Coalition to Eliminate HBV, Dr Tavis works on the front line of researching new developments in HBV treatments.
Dr Tavis says the cure to HBV is coming. “The feeling within the scientific community is that major improvements will happen somewhere in the next five to 10 years… [but] it isn’t going to be one optimal combination at first.”
“The best way to cure any disease is the one-two-punch,” Dr Tavis says. “It’s always better to stop a problem before it starts… [then] the drugs are needed as a mop-up crew.”
Instead of the cure being a singular treatment or a singular element, like the kryptonite that threatens to destroy Superman, Dr Tavis says the cure to HBV will likely be a collection of powerful tools that together will have the strength to take on the virus.
Scientists all over the world are making huge advancements in new treatments that can “attack the virus from every angle”, he explains.
Like a squadron of disease-demolishing superheroes, some of the therapies in development focus on blocking the virus entering the cell in the first place, whilst others deactivate the DNA. There is one therapy that will distort the shell of the virus so HBV becomes inactive and unable to survive. Another will lock itself to the genetic material of the virus and either cause it to fall apart or stop it from working.
Clinical trials are underway to investigate how these various treatments can be combined to work safely and effectively with one another, so healthcare professionals will be able to pick from a “toolbox” of therapies to deliver patient-specific treatment. One pharmaceutical company, Replicor, is already doing it. Using a three-part combination of drugs, Replicor is achieving a functional cure rate of 35% in early clinical trials.
“The one-two-punch”
Dr Tavis feels excitement about the advancing therapies and intense gratitude toward his colleagues and the scientific community. To keep this momentum, he said funding must continue to be pushed toward HBV research, so scientists on the home stretch can get to the finish line.
“There’s hope,” he said. “We need to push hard, and we need advocacy… we need to keep the motivation and support from governments and foundations around the world.”
Despite the excitement about the prospect of finding an HBV cure, vaccinating against HBV remains the single best way of vanquishing the virus, since the treatment is largely inaccessible for most HBV sufferers.
“The best way to cure any disease is the one-two-punch,” Dr Tavis says. “It’s always better to stop a problem before it starts… [then] the drugs are needed as a mop-up crew.”
More than two-thirds of the now 6.3 million children below the age of five with hepB live in 47 African countries. This is especially concerning since hepB becomes chronic in nearly 95% of infants and children who contract the virus, compared to only 5% of newly infected adults. In these countries, mother-to-child transmission – or vertical transmission – is the most common mode of way hepB is passed on.
To reduce vertical transmission of the virus, a dose of hepB vaccination is recommended within 24 hours of birth. In 2021, less than 20% of newborns across Africa received this birth dose of vaccination and only 14 countries in the region had national policies for hepB birth dose vaccination.
Earlier studies from Asia and North America have shown that the birth dose vaccination can reduce vertical transmission, however a lack of data from Africa on the effectiveness of birth dose vaccination contributes its low uptake in the region, where the epidemiological characteristics are different.
As a father of two sons who both grew up to become scientists themselves, Dr Tavis feels a personal connection to the importance of making HBV vaccines accessible to every child. Recalling the feeling of holding his sons as babies, and the parental instinct to protect their delicate human lives, he says, “You just want to put a force field around them to protect them, and that’s essentially what a vaccine does.”
“We need to go pedal to the metal on this. It needs to be 100% delivery.”
The HepVir team, which has been working on various hepatotropic viruses (mainly HBV and HDV, but also HEV and HCV) for many years, has recently obtained a grant from MSD-Avenir France to reinforce a thematic of research on “HBV RNA biogenesis: from understanding to therapeutic applications.”
Two positions (for one “experienced” post-doctoral fellow and a starting doctoral fellow), each funded for 36 months, are therefore available in the team to work on this program, together with a 100%-involved engineer, and in link with other members of the team. Details on the program will be given upon exchanges with us. In short, unbiased methodologies will be applied to identify host factors involved in the regulation of HBV RNA biogenesis during the natural course of infection and also after therapeutic intervention.
For more information on the position and how to apply, please download the position description by clicking on the button below.
The urgent need for improved Hepatitis B virus (HBV) biomarkers – indicators found in blood, bodily fluids or tissue used to measure disease progression and response to treatment – has been considered in a seminal roadmap publication ahead of World Hepatitis Day this Thursday, 28 July.
Published in Nature Reviews – Gastroenterology & Hepatology, the roadmap authored by 29 world-leading experts in HBV research, clinical practice, the pharmaceutical and biotech industries, analyses the strengths, weaknesses and opportunities of serum HBV biomarkers.
Roadmap co-lead author University of Melbourne Professor Peter Revill, a lab head at the Victorian Infectious Diseases Reference Laboratory (VIDRL), Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity (Doherty Institute) said new biomarkers are needed to better follow HBV infection in patients.
“As promising new drugs for treating hepatitis B become available, we urgently need new biomarkers to reliably monitor the effectiveness of these treatments in our patients,” Professor Revill said.
“This roadmap – the first of its kind in the academic literature on HBV – has identified the path forward for academia, clinicians and industry to secure better serum biomarkers.”
296 million people are infected with HBV globally and about one million people die each year from HBV-related causes, including liver cancer. While a preventative vaccine and antiviral therapies to suppress HBV are available, there is no cure.
All member states of the World Health Organization have committed to the goal of eliminating viral hepatitis as a public health threat by 2030.
In October 2020, as the global COVID-19 pandemic restricted travel worldwide and threatened to stymie the promising progress from the previous year’s International HBV meeting in Melbourne, Australia, the International Coalition to Eliminate Hepatitis B Virus (ICE-HBV) held virtual interactive workshops on HBV biomarkers.
HBV experts from academia, clinical practice and the pharmaceutical industry participated in webinars and panels, discussing the usefulness of both classic and emerging viral and immunological serum biomarkers to monitor HBV infections, disease progression and responses to current and new treatments.
“Crucially, HBV has a reservoir of covalently closed circular DNA (cccDNA, a mini-chromosome) in the nucleus – and this reservoir is not targeted by current therapies,” Professor Revill explained.
“This poses a real challenge, as the only means of analysing this reservoir is to subject our patients to liver biopsy.”
The roadmap recognises that liver biopsies will be increasingly difficult to undertake, and serum biomarkers are necessary as surrogate markers of activity in the liver.
Roadmap co-lead author, University of the Witwatersrand Professor Anna Kramvis, Director of the Hepatitis Virus Diversity Research Unit, School of Clinical Medicine at University of the Witwatersrand, said that challenges and opportunities, including increasing demand on healthcare systems, patient hesitancy, promising immune response enhancing treatments and future disruptions like the COVID-19 pandemic, underscore the urgent need for alternative HBV biomarkers.
“Emerging treatments to improve patients’ immune responses to fight HBV will require better serum biomarkers in order to reduce dependence on liver biopsies” Professor Kramvis said.
“Hepatitis B is an immune mediated disease and people living with chronic HBV experience a reduced immune response to the virus and infected cells. As the pharmaceutical industry explores treatments to enhance this suppressed immune response, we will need serum biomarkers to observe the effectiveness of these treatments more easily.”
Developing alternative methods, to analyse serum biomarkers and to monitor cccDNA in the liver, would assist pharmaceutical producers and clinicians in monitoring the effectiveness of new treatments to induce functional cure, defined as the loss of HBV surface antigen, which allows a patient’s immune system to fight and reduce HBV in the body.
The roadmap also considers the promise of emerging technologies to replace existing liver biopsy methods.
“Fine needle aspirants (FNA’s) use an even smaller needle than those used for current liver biopsies, that are much easier to administer – far less impactful and invasive on the patient,” Professor Revill said.
“Immunologists have discovered that you can get a lot of useful information about HBV from these FNA’s.”
The roadmap also notes the importance of working closely with the HBV-affected community to develop cure strategies for patients.
Engagement with the HBV-affected community worldwide is critical to ensure equitable access to new therapies for all who need them, Professors Revill and Kramvis agree.
Professors Revill and Kramvis are grateful for the input of their fellow roadmap authors, who presented papers, chaired sessions, and participated in panel discussions at the workshop.
“The roadmap demonstrates a truly collaborative global effort to summarise our knowledge on current biomarkers, emerging biomarkers, and identifying what the field of HBV research and treatment needs to move forward as we work toward our shared goal of eliminating viral hepatitis in the foreseeable future.”
Register to attend the International HBV Meeting by Friday, August 26, 2022.
Registrations: This year’s meeting will take place both onsite in Paris, and online. Be sure to register before the final registration deadline of August 26. Payments are accepted via credit card, check, and wire transfer.
Accommodations:
Special conference accommodation rates at the Novotel Paris Centre Tour Eiffel have been negotiated for delegates and are only available when booked through the Registration Portal. To reserve accommodations at the Novotel Paris Eiffel Tour Hotel please click here.
Due to extremely high demand, the deadline to reserve hotel accommodations via the HBV Meeting website is now Friday, August 12 at 3 p.m. EDT.
Please note – payment via credit card is due at the time of booking. Payments via wire transfer or US check are due within 7 days of making the reservation.
Social Event:
Please join us for a night of dinner cruise and dancing on the river Seine on Wednesday, September 21! Please purchase tickets for this event directly on the registration form. If you did not purchase a ticket for the dinner cruise during the registration process, but would like to purchase a ticket for you, or a guest, please email info@hbvmeeting.org. Boarding will begin at 7:30pm. The cruise will be 2.5 hours from 8:30 pm – 11:00pm. You won’t want to miss it!
We are delighted to share our HBV Serum Biomarkers manuscriptm, recently published online at Nature Reviews Gastroenterology and Hepatology. This publication is an important review, which culminates almost 2 years work since the ICE-HBV Serum Biomarkers workshops online in 2020.
Globally, 296 million people are infected with hepatitis B virus (HBV), and approximately one million people die annually from HBV-related causes, including liver cancer. Although thereis a preventative vaccine and antiviral therapies suppressing HBV replication, there is no cure.Intensive efforts are under way to develop curative HBV therapies. Currently, only a few biomarkersare available for monitoring or predicting HBV disease progression and treatment response. Asnew therapies become available, new biomarkers to monitor viral and host responses are urgentlyneeded. In October 2020, the International Coalition to Eliminate Hepatitis B Virus (ICE-HBV) helda virtual and interactive workshop on HBV biomarkers endorsed by the International HBV Meeting.Various stakeholders from academia, clinical practice and the pharmaceutical industry, withcomplementary expertise, presented and participated in panel discussions. The clinical utility ofboth classic and emerging viral and immunological serum biomarkers with respect to the courseof infection, disease progression, and response to current and emerging treatments was appraised.The latest advances were discussed, and knowledge gaps in understanding and interpretationof HBV biomarkers were identified. This Roadmap summarizes the strengths, weaknesses,opportunities and challenges of HBV biomarkers.
has been involved for nearly ten years in research programs aimed at curing hepatitis B virus (HBV) and Delta virus (HDV) infections. Every year, the ANRS HBV Cure Task Force organizes a workshop bringing together international experts to discuss the recent advances in our understanding of chronic hepatitis B and Delta, and to present the progress in the discovery of new therapeutic targets and advances in clinical development. On the occasion of World Hepatitis Day on July 28th 2022, Fabien Zoulim, professor of medicine in Lyon, coordinator of the European project “IP-cure-B”, the RHU project “CirB-RNA”, the ANRS Task Force “HBV Cure” and current chair of ICE-HBV presents the take home messages from the 9th HBV cure workshop held in Lyon on July 5th, 2022.
Background: Despite the fact that an effective vaccine is available, hepatitis B still represents a major global public health problem today. According to the WHO, there were still 296 million chronic carriers of the virus worldwide in 2019; this disease is also the leading cause of liver cancer. HBV and its complications contributed to 820,000 deaths in 2019. Co-infection with HDV worsens the disease and increases the risk of developing cirrhosis or liver cancer. There are currently no curative treatments for these two types of hepatitis.
Advances in understanding the mechanisms of HBV persistence
Virological aspects. Recent data concerning the viral reservoir (HBV cccDNA) were presented during the workshop. Recent data were presented on how this reservoir is formed and regulated during chronic infection, and how it could be targeted, in particular by using new “genetic scissors” approaches.
Immunological aspects. Recent data were discussed on the mechanisms involved in the defects in the immune responses of patients to discover novel pathways to restore them to effectively control or eliminate the virus. In particular, new approaches such as therapeutic vaccines were discussed.
New technologies to assess the site of infection (hepatic compartment), the viral reservoir and the hepatic immune response
The evaluation of the hepatic compartment at the virological and immune levels is critical to determine the impact of the new therapeutic approaches on the viral reservoir and on the antiviral immune responses in the site of infection. Experts have studied new approaches to analyze the liver compartment, which are less invasive than liver biopsy, such as fine needle aspirations. New PCR and immunology technologies allow now to investigate the viral reservoir and immune responses on FNA samples in proof of concept clinical trials. This should generate crucial information for the development of new therapeutic approaches.
Overview of advanced therapies in the field of hepatitis B and HBV-HDV co-infections
A comprehensive review of the most recent clinical trials was presented and has shown that this field of research is very dynamic: many antiviral molecules and several immunotherapy strategies are in phase II clinical trials, most often in combination therapy, either with direct antivirals or with direct antivirals and immunotherapy. Great advances have been made on certain classes of molecules such as capsid assembly modulators and on strategies targeting viral RNAs (siRNAs or antisense oligonucleotides).
For hepatitis Delta, a virus entry inhibitor (bulevirtide) has been conditionally approved by the European Medicines Agency (EMA) in July 2020- taking into account that so far no treatment was available for this disease. The modalities of administration are being developed pending the results of phase III clinical trials. Other antiviral molecules are also being studied in various clinical trials.
The ANRS | Emerging infectious diseases sponsors and funds a Delta cohort study, ANRS HD EP01 BuleDelta, (monitoring of HDV patients on bulevirtide) which has already included 193 patients in 30 centers. It is also sponsoring the IP-Cure-B study (ANRS HB07 IP-Cure-B ), an European-funded randomized clinical trial which aims to stimulate antiviral immune responses by a TLR8 agonist (Selgantolimod) and which has already included 6 patients in France.
ICE-HBV is working on an international collaborative research review project about HBV management in resource-limited settings (RLS), led by Daryl Lau and Manal El Sayed. The main objective of the project is to improve access to/quality of HBV care in RLS and reduce HBV mortality and incidence.
We are therefore inviting individuals and organizations working on HBV in resource-limited settings to complete a surveydeveloped to elaborate improved Point-of-Care models for HBV management in RLS. Your input will inform our work on this pressing topic. The survey should take around 15-20 minutes and can be found in the links below:
