$24M US grant to back global team working toward hepatitis B cure
Scientists from Johns Hopkins Medicine to lead multinational consortium
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Backed by millions in U.S. funding, scientists from Johns Hopkins Medicine in Baltimore will be leading a new international consortium working to find a cure for hepatitis B — a viral infection that can set the stage for serious complications, such as liver failure or liver cancer — the university announced.
“The World Health Organization estimates that some 300 million people worldwide are already infected with hepatitis B virus, with more than a million new cases added each year — strong evidence that the efforts of our consortium are greatly needed,” Chloe Thio, MD, an infectious disease expert and leader of the consortium at Johns Hopkins, said in a university news story.
The newly-formed consortium was awarded a five-year, $24 million grant from the National Institute of Allergy and Infectious Diseases, a branch of the National Institutes of Health (NIH). The team will involve scientists in the U.S. as well as Brazil, India, Senegal, and Uganda.
The hepatitis B virus, known as HBV for short, is spread by contact with bodily fluids and infects the liver, leading to liver inflammation or hepatitis. In some individuals, especially people infected as children, HBV infection leads to a long-lasting or chronic infection that causes ongoing liver damage, setting the stage for life-threatening complications that include liver cancer.
“Although hepatitis B can be prevented by a safe and effective vaccine given shortly after birth, it’s still a major health problem worldwide, especially in areas such as the Western Pacific and Africa, where access to the birth-dose vaccine is more limited,” Thio said.
The scientists noted that, once the chronic infection is established, there is no way to cure it.
First goal: Enroll patients with chronic hepatitis B
The first major goal of the newly formed consortium is to enroll two groups of patients: 225 with chronic hepatitis B, and 450 who are chronically infected with not only the HBV, but the human immunodeficiency virus (HIV).
Both viruses have overlapping transmission routes, and as many as 10% of people living with HIV infection around the world are estimated to also have hepatitis B. Coinfection accelerates the progression to advanced liver disease and increases the risk of liver-related death.
The 675 total participants will serve as the pool for the consortium’s studies, which will involve the collection of samples, such as liver tissue, blood, and circulating immune cells.
“Once the first aim of the consortium — building the [patient groups] and establishing the HBV clinical and specimen repository — is completed, the second aim will be to begin studying these specimens to advance an HBV cure,” Thio said. “Such studies also involve building research capacity at each of the collaborating centers and training early-stage investigators, providing a pipeline of researchers focused on finding an HBV cure.”
Once all of these resources are in place, the third goal of the consortium will be to better understand, using new techniques, how HBV infects liver cells, integrates its genetic information into the cells’ DNA, and persists in the liver.
This [work] could provide crucial information needed to develop a functional [hepatitis B virus] cure, and in people living with HBV and HIV, inform how HIV affects such an HBV cure.
Then, building off findings from all these efforts, the researchers will analyze data collectively to characterize how both the virus and the body’s immune system behave during HBV infection.
“The focus will be on identifying people with good control during treatment by looking at blood levels of hepatitis B surface antigen [HBsAg], a protein on the surface of the HBV used to diagnose active infections and monitor response to therapy,” Thio said.
The consortium’s researchers will span seven broad components. For example, the multiomics core will conduct genetic sequencing and comprehensive protein analyses, while the immunology core will focus on immune responses during treatment. The translational core, meanwhile, will focus on viral activity in response to treatment.
Thio is heading up the virology core, which aims to identify markers to track HBV growth and activity. By combining these new markers with changes in HBsAg levels during treatment, the researchers expect to build a multi-layered mechanistic model to control HBV infection.
“This could provide crucial information needed to develop a functional HBV cure, and in people living with HBV and HIV, inform how HIV affects such an HBV cure,” Thio said.
