September 12, 2012

Hepatitis C fight - 'watershed moment'

Erin Allday
Published 5:16 p.m., Tuesday, September 11, 2012

Earlier this year, an editorial in the New England Journal of Medicine declared that the world was in a "watershed moment" in the history of treatment for hepatitis C, a virus that is believed to infect roughly 180 million people globally. Dr. Warner Greene, director of the Gladstone Institute of Virology and Immunology in San Francisco, agrees wholeheartedly - and believes that with recent advances in treatments and a cure, the world could be on the cusp of nearly wiping out the virus.

Q: What does the hepatitis C virus do to the body?

A: This is an RNA virus that infects hepatocytes, cells in the liver. That's why you ultimately get hepatitis, or inflammation in the liver, and that can progress on to cirrhosis. About 20 percent of people spontaneously clear the hepatitis C virus, and of the rest, about 20 to 25 percent will progress to cirrhosis, and eventually end-stage liver disease. Hepatitis C is the leading reason behind liver transplants in the United States.

Q: For many years, hepatitis C has been treated with interferon. What is interferon?

A: Interferon is a type of protein called cytokine. It normally triggers an antiviral response in the body. It inhibits key steps in the (hepatitis C) virus life cycle that allow it to replicate. But it's doing it at a cost. Cytokine is pretty toxic. It makes patients very sick.

Q: Last year the Food and Drug Administration approved new drugs to treat hepatitis C. How do they work?

A: It's just like with HIV - you're attacking multiple, key proteins needed for the hepatitis C virus lifecycle. Now you have these small molecules that are attacking the virus itself, as opposed to trying to induce an antiviral response, like with interferon.

These drugs are proving to be just dynamite. We're very close to being able to cure everybody of hepatitis C. The natural history of hepatitis C virus infection has been fundamentally changed.

Q: Why has hepatitis C been so hard to treat historically?

A: One thing that limited progress was the lack of an infectious molecular clone to use in the laboratory to test drugs. It was only in the last few years that an infectious molecular clone came out of Japan. Before that, none of them fully replicated (in the lab). When the molecular clones came along progress just took off at light speed.

Then the blueprint for working on HIV became very informative - protease inhibitors, polymerase inhibitors, they were all targeted very quickly, by multiple pharmaceuticals. Many of the pharmaceuticals just moved their HIV discovery teams into HCV. Progress has been made so rapidly here because the trail had been blazed by all of the HIV drugs.

Q: Will we be able to wipe out hepatitis C entirely?

A: In contrast to HIV, we do have the capability of doing that - essentially curing everyone who got infected. While we have made tremendous progress against HIV, we still don't have a cure, we still don't have a vaccine. The situation for HCV is dramatically different. A cure is achievable. Someday soon, the cure using an interferon-free cocktail is going to be routine.

Then it becomes more of an implementation issue - how you distribute these drugs, what you charge for them. There are 180 million people infected worldwide, five to six times the size of the HIV epidemic, and many are living in resource-poor settings. We're going to have to figure out how to deal with the developing world.

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