Digging into a decades-old hepatitis B mystery suggests a new potential treatment

In their effort to answer a decades-old biological question about how the hepatitis B virus (HBV) is able to establish infection of liver cells, research led by Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center (MSK) and The Rockefeller University identified a vulnerability that opens the door to new treatments.

The team successfully disrupted the virus’s ability to infect human liver cells in the laboratory using a compound already in clinical trials against cancer — laying the groundwork for animal model studies and potential drug development based on their insights, according to findings published Feb. 20 in Cell.

Hepatitis B is a liver infection that affects almost 5% of the world’s population. It causes long-term damage to liver cells and is one of the leading causes of liver cancer. More than 250 million people worldwide have chronic HBV infections and the virus causes more than 1 million deaths a year, making it the second most deadly infection worldwide, according to the World Health Organization.

The research was led by hepatologist and virologist Dr. Robert Schwartz at Weill Cornell Medicine, chemical biologist Dr. Yael David at MSK and Dr. Viviana Risca at The Rockefeller University.

“This project started from our fundamental interest in how the virus’s chromosomes might look and function and led to unexpected discoveries of how the viral infection is established in human cells,” Dr. David said.

Study first author Dr. Nicholas Prescott, pursued the research in the David Lab as his graduate thesis. “This is a great example of how investment in ‘basic science’ and investigation of fundamental biological questions can open the door to medical advances,” he said. “I always thought I’d be working on questions that decades later someone might cite in a paper when they come up with a cure for some disease. Never in a million years did I expect to lead a project that identified such a strong candidate for drug development for a global scourge like hepatitis B.”

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MORE HEPATITIS B RESEARCH UPDATES:

• OHSU scientists develop first transgenic model for hepatitis B research

Researchers at Oregon Health & Science University have developed the first transgenic nonhuman primate model — genetically modified to carry a human gene — for studying hepatitis B virus. The breakthrough could lead to the development of new treatments for the disease, which affects about 250 million people globally and results in nearly 1 million deaths annually.

The findings were published in the Proceedings of the National Academy of Sciences.