Scientists may have figured out why some people infected with liver-destroying hepatitis C essentially cure themselves: Their genes seem to unleash a faster immune attack.
The research, reported Thursday in the journal Science, may point to new ways to prevent or treat hepatitis C, widely considered the most serious of a family of liver viruses.
About 20 percent of people infected with hepatitis C somehow clear the virus from their bodies without treatment. But about 3 million Americans and 180 million people worldwide remain chronically infected, at risk of eventually developing liver cancer or failure. The virus claims 10,000 to 12,000 U.S. lives annually.
Doctors have long hoped that learning why some people are lucky enough to spontaneously recover might help them create a vaccine to prevent hepatitis C.
Now research by a team of U.S. and British scientists suggests one key to that recovery is genes that take the brakes off the body’s front-line immune defense, so-called natural killer cells.
The work won’t benefit patients any time soon.
However, “It brings us closer to understanding how the virus works,” said Dr. Chloe Thio of Johns Hopkins University, who co-authored the study with researchers from Britain’s Southampton University and the U.S. National Cancer Institute.
“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 don’t 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.
But how would an immune-inhibiting system fight hepatitis?
Natural killer cells take action
When the body senses viral infection, it has to activate the natural killer cells by switching off inhibiting receptors, Thio explained. This KIR combination seems weak, “so it’s easier to overcome,” she said.
There’s a caveat: 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 here 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 noted that 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.