Certain genes make it easier for some people to fight hepatitis C

Friday, August 6th 2004, 6:18 am

By: News On 6

WASHINGTON (AP) _ Genes that take the brakes off the immune system may help explain why some people essentially cure themselves of liver-destroying hepatitis C, research suggests.

Hepatitis C is widely considered the most serious of a family of liver viruses. Yet 20 percent of those infected clear it from their bodies without treatment.

Solving that mystery could point to new ways to treat hepatitis C or, more important, develop a vaccine to prevent it.

Research by a team of U.S. and British scientists suggests the key is being lucky enough to inherit a specific gene combination that lets the body more quickly unleash its front-line defense _ natural killer cells.

The research, published Thursday in the journal Science, will not immediately benefit the 3 million Americans and 180 million people worldwide who remain chronically infected with hepatitis C. The virus leaves them at risk of eventually developing liver cancer or failure, and claims 10,000 to 12,000 lives a year in the United States.

``It brings us closer to understanding how the virus works,'' said Dr. Chloe Thio of Johns Hopkins University, co-author of the study with researchers from Britain's Southampton University and the National Cancer Institute in the United States.

``In the long term, whether we can use this information to modulate the body's immune system to improve therapeutics or vaccine design _ that is the ultimate goal,'' she said.

Hepatitis C studies in chimpanzees suggested natural killer cells were more active in animals that recovered. To find the genes involved in that immune response, the researchers analyzed the DNA of 1,037 hepatitis C patients, 352 of whom spontaneously recovered.

Natural killer cells are continually poised to attack if a virus strikes. Inhibitory receptors called KIRs (pronounced ``keers'') keep them in check between infections, to ensure they do not attack healthy tissue.

The scientists discovered a particular gene combination that controls one KIR receptor, and the molecule attached to it was twice as common in recovered patients than in the still-infected.

How would an immune-inhibiting system fight hepatitis?

When the body senses viral infection, it has to activate the natural killer cells by switching off inhibiting receptors, Thio said. This KIR combination seems weak, ``so it's easier to overcome,'' she said.

The genetic protection was found only in patients thought to have received an initial low dose of hepatitis C because they were infected by contaminated drug or tattoo needles instead of a blood transfusion. It may be that the extra virus from tainted blood _ long a common cause of hepatitis C _ was simply too much for those patients' first-line defenses to handle, Thio said.

Since 1992, the U.S. blood supply has been strictly tested for hepatitis C, so new transfusion-related cases have plummeted. Today the disease is most commonly spread in the United States through injecting drug use.

Other factors also play a role in spontaneous hepatitis C recovery, Dr. Peter Parham of Stanford University said in an accompany editorial.

But he said doctors already help treat a type of leukemia by releasing natural killer cells from a different KIR receptor, so the question now is whether a similar strategy could be developed for hepatitis.