Researchers Develop Model To Test New Hepatitis B Treatments

By C. Rajan, contributing writer

MIT researchers have developed a new technique for studying the lifecycle of the hepatitis B virus, which could help in testing new treatments for the disease.

Sangeeta Bhatia, Howard Hughes Medical Institute investigator at MIT, and Charles Rice of Rockefeller University, used micro-fabricated cell cultures to sustain the hepatitis B virus in human liver cells, allowing them to study immune responses and drug treatments. The results are reported in a paper published this week in the journal Proceedings of the National Academy of Sciences.

The hepatitis B virus (HBV) infects about 400 million people globally and is a major global health problem. It can cause chronic liver disease, and lead to liver cirrhosis and liver cancer. According to the World Health Organization (WHO), nearly 800,000 people die every year due to the acute or chronic consequences of hepatitis B.

There is an effective hepatitis B vaccine available for preventing infection and its chronic consequences; however, only around 50 percent of people in some hepatitis B prevalent countries are vaccinated. Furthermore, the vaccine is not as effective once a person has already been infected. A complete cure for the disease is very rare in persons with chronic infection.

"Once a liver cell is infected, the viral genome persists inside the nucleus, and that can reactivate later," says Bhatia, who is also the John and Dorothy Wilson Professor of Health Sciences and Technology. "So although we have a vaccine, it's important to find a way to study this persistent form of the virus to try to identify treatments that could efficiently clear it."

In order to develop and test new treatments for HBV, scientists need to study the infected liver cells (hepatocytes), so they can understand how the virus interacts with them. The difficulty lies in keeping the infected hepatocytes alive long enough to study the virus. "That's because the hepatocyte — the main cell in the liver — is unstable," Bhatia says. "It's a very finicky cell, and when you isolate it from the liver and try to culture it under conventional conditions, it rapidly loses its repertoire of liver functions."

To keep the liver cells stable and functioning long enough to monitor their response to the virus and antiviral drugs, Bhatia and her team developed a technique where the hepatocytes are first patterned onto surfaces covered in dots of collagen and then are surrounded by connective tissue made up of stromal cells, which support the hepatocytes in carrying out their liver functions. When the researchers monitored the response of the cells to two existing drugs, they found that the infected cultures responded to the drugs in the same way that liver cells inside the body do.

With this model system, the researchers now plan to begin using it to investigate new treatments for HBV, and also to study liver cells' natural antiviral response in more detail.

This research follows another report earlier this year from German researchers who discovered a new mechanism of defense against HBV, which could also open up new treatment possibilities.