Worldwide, 257 million people (3.5% of the population) are chronically infected with hepatitis B virus (HBV) and, even though a prophylactic vaccine and effective antiviral therapies have been developed, there is no cure. While vaccination efforts are substantially slowing down incidence in most countries, HBV infections are still rising.

HBV kills more people than malaria, with chronic HBV (CHB) infection resulting in more than 880,000 deaths per year from cirrhosis and liver cancer. No cure for CHB exists due in part to the continued presence of a viral reservoir which is not targeted by current therapies. CHB persists despite the best treatment, and risks of liver cancer remain. Current treatments for CHB must generally be taken for life to remain effective and only 8 per cent of people who need treatment have access to them.

Despite the huge human and economic toll of chronic HBV infection, HBV research has been largely underfunded compared to other diseases. Enhanced investments could make a big difference, create important resources savings from treatment scale-up, and ensure that improved treatments prevent adverse outcomes in all patients.

Recent technological advances have led to the development of a cell culture model of persistent HBV infection. This makes it possible, for the first time since the discovery of HBV, to study the mechanisms that control the biogenesis, homeostasis and decay of its covalently closed circular DNA (cccDNA) transcriptional template, and to exploit that information to eradicate HBV from infected cells. Targeting this viral reservoir will be the key to curing CHB. We believe that given recent scientific progress in HBV research and the momentum created by hepatitis C cure discoveries, governments, foundations and other research sponsors should work together to accelerate HBV cure research now.

In 2016, a group of prominent scientists published a “call to arms” manuscript suggesting a coordinated global approach to HBV cure was urgently required. This generated substantial interest which led to the formation of the International Coalition to Eliminate Hepatitis B (ICE-HBV) in September 2016, ratified at the International HBV Meeting in Seoul.

Organisational structure of ICE-HBV and the international scientific working groups.

ICE-HBV aims to support the discovery of a safe, affordable, scalable and effective cure, available to all persons living with CHB. Modelled on the highly successful HIV cure initiative, ICE-HBV has established international working groups that are focusing on virology, immunology and the development of innovative tools. These groups identify research gaps and perform research that will hopefully lead to development of an HBV cure. Composed of leading basic and clinical science academic researchers from five continents, they are currently working together to identify and develop, among others:

• standardised protocols for quantitative cccDNA measurement;
• vulnerabilities in cccDNA biology that can be exploited for curative therapeutic purposes;
• curative immunobiological and direct antiviral strategies
• biomarkers of HBV immunopathogenesis, disease progression, treatment response and markers predictive of a durable cure.

Areas targeted for HBV cure research.

The first tangible outcome of ICE-HBV will be to publish a consensus statement that will be in effect a “road map” towards HBV cure to guide the field. Through engagement with key stakeholders, ICE-HBV will also drive changes in governmental policy to ensure more funds are channelled to HBV cure research and drug development. Through consultation with affected communities, ICE-HBV will appropriately answer the needs of patients. Through coordination with existing initiatives, such as the HBV Forum, ICE-HBV will engage with industry and regulatory agencies in the most collaborative and efficient manner. To learn more: www.ICE-HBV.org

By the ICE-HBV Governing Board:

Capucine Penicaud, MSc, MA, Australia (Program Manager, Ex-Officio)

Fabien Zoulim, MD, PhD, France (Deputy Chair)

Massimo Levrero, MD, Italy

T. Jake Liang, MD, United States

Stephen Locarnini, PhD, Australia

John Tavis, PhD, USA

Frank Chisari, MD, USA (Honorary President)

Peter Revill, PhD, Australia (Chair)