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Cure for Hepatitis B Pushed

— Disease affecting 257 million people needs better treatment

MedpageToday

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VIENNA – The International Liver Conference kicked off here today with a push to find a cure – not just maintenance treatment – for the one quarter billion people living with hepatitis B virus (HBV) infection, but researchers said that finding a cure could be elusive, and it certainly won't come quickly.

"I think we are still at least 3 years away from starting a Phase III clinical trial that would probably include a combination therapy," said Massimo Levrero, PhD, a member of the governing body of the International Coalition to Eliminate HBV (ICE-HBV) and director of the Cancer Research Centre of Lyon in France.

Levrero, one of several participants in a press conference at the start of the 5-day annual meeting of the European Association for the Study of the Liver, told app that there are numerous drug treatment candidates being tested to attack various structures of the virus, but he compared HBV to HIV rather than hepatitis C virus – for which an 8-week functional cure is now available.

"Hepatitis B is very different than hepatitis C, and it is very difficult to eradicate, as is HIV," he said.

While HIV eradication is very rare – with only two known and verified cures worldwide, hepatitis B has been cured by various methods – but in less than 10% of cases, said Peter Revill, PhD, senior medical scientist at the Victorian Infectious Diseases Reference Laboratory in Melbourne, Australia. At the press conference, Revill suggested that as many as one million people in the world have been cured of hepatitis B – but there are an estimated 257 million people living with hepatitis B infection.

Revill said that more than 887,000 deaths are caused by the virus every year. Chronic HBV causes almost 40% of cases of hepatocellular carcinoma, which is the second leading cause of cancer-related mortality worldwide. The most affected areas of the world for hepatitis B infection are Africa and Asia, but the disease is found throughout the world.

He noted that antivirals can suppress the virus but do not affect the risk of causing liver cancer. Levrero said that when people have to take drugs for long periods of time – sometimes decades in the case of HBV treatment – there is a waning of compliance, which makes the need for a cure more imperative.

The ICE-HBV initiative was the subject of a think tank discussion as well as the press briefing; the conference was expected to attract 8,000 physicians, researchers, scientists, and allied healthcare professionals. Along with its presentation, the strategy was published simultaneously online in .

'Global Public Health Challenge'

"Chronic HBV infection is a global public health challenge on the same scale as tuberculosis, HIV, and malaria," Revill and colleagues said. "ICE-HBV is a coalition of experts dedicated to accelerating the discovery of a cure for chronic hepatitis B. Following extensive consultation with more than 50 scientists from across the globe, as well as key stakeholders including people affected by HBV, we have identified gaps in our current knowledge and new strategies and tools that are required to achieve HBV cure."

"We believe that research must focus on the discovery of interventional strategies that will permanently reduce the number of productively infected cells or permanently silence the covalently closed circular DNA in those cells, and that will stimulate HBV-specific host immune responses which mimic spontaneous resolution of HBV infection," the team continued. "There is also a pressing need for the establishment of repositories of standardized HBV reagents and protocols that can be accessed by all HBV researchers throughout the world."

Revill noted that although vaccination against HBV is effective, vaccination cannot eradicate the disease in people who are already infected: "Once chronic infection is established, patients are exposed to significant risk of liver disease including chronic hepatitis, cirrhosis, and hepatocellular carcinoma," he said. "The natural history of chronic HBV infection usually consists of up to five stages, which differ in the level of viral replication, viral antigen expression, and inflammatory activity in the liver."

The investigators concluded: "The time for development and implementation of a safe, affordable, widely available cure for chronic hepatitis B virus infection is now. HBV research funding has for too long been woefully inadequate; this must be addressed. ICE-HBV seeks to achieve its goals by fostering collaborative partnerships with researchers (both within the HBV field and outside), clinicians, the pharmaceutical industry, and a range of stakeholders, including communities affected by chronic hepatitis B; we invite these groups to join forces with ICE-HBV in a global effort to discover, develop, test, and implement HBV cure strategies, to help ensure that the WHO goal of HBV elimination as a public health threat by 2030 is achieved."

Disclosures

The research was supported by the Australian Academy of Science, France Recherche (ANRS), and the Peter Doherty Institute for Infection and Immunity, and supported in part by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases.

Revill disclosed relevant relationships with Gilead Sciences; Levrero reported relevant relationships with Bristol-Myers Squibb, ContraVir, Galapagos, Arbutus, Gilead, Janssen, Roche, and MSD.

Primary Source

The Lancet Gastroenterology & Hepatology

Revill P, et al "A global scientific strategy to cure hepatitis B" Lancet Gastroenterol Hepatol 2019; DOI: 10.1016/S2468-1253(19)30119-0.