Bad Blood Print
Written by Justin Reedy   
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ImageThe rest, about 55 to 85 percent, have the “chronic” form of the virus, which can hang around for years without causing any conspicuous signs of infection. They may have fatigue, or rare nausea, or other vague symptoms that don’t point to a particular cause. If they're engaging in risky behavior, such as IV drug use, they may unknowingly pass the virus on to others, like someone who doesn't know they're HIV-positive having unprotected sex or sharing dirty needles.

“Many are diagnosed based on routine blood screening and are very surprised to know they’re infected,” Larson explains. “Some people are diagnosed because they reported to their doctor a history of risk factors—like transfusions before 1992, or IV drug use—or they were incidentally noted to have abnormal liver enzymes on routine lab tests.”

Some people may not realize they have the virus at all, and could carry it their entire lives without knowing. Of the estimated three million people in the United States with chronic hepatitis C infection, between 20 and 40 percent will eventually develop cirrhosis or scarring of the liver.

Medical experts believe that in the next decade, the burden of the disease on society will grow as more and more longtime carriers of the virus begin developing cirrhosis and liver disease.

But hepatitis C is not a death warrant. The disease is treatable, at least for most patients. The early-stage acute infection can be cured in most people, if it’s caught then. But even in patients with the chronic infection, such as Naomi Judd, there are treatment options that can eliminate the virus from their bodies entirely.

The artificial version of interferon, a compound made by the body to fight infection, can help hepatitis C patients by improving the body’s immune response against the virus. Since the virus makes billions and billions of copies of itself every few hours—a discovery made by Gretch and his UW colleagues—researchers have developed a time-release interferon treatment to deal with this rapid regeneration.

Now, most chronic hepatitis C patients receive a combination of interferon and ribavirin, a drug that interferes with virus reproduction. The combination therapy can cure many patients of the virus, depending on the type of hepatitis C they’re carrying.

Unfortunately, only about half of the patients with one strain of the virus will respond to the combination therapy. The others will continue to carry the virus, and some may eventually develop liver cirrhosis and end-stage liver disease.

The only known treatment at that point is a difficult yet potentially lifesaving one for patients: a liver transplant. UWMC is a regional center for liver transplants, and is one of only two such hospitals in the northwestern United States. UW doctors performed 124 liver transplants last year, and could have performed many more if there were more liver donors. About two thousand Americans die each year while waiting for a liver transplant.
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ImageNow that physicians have followed hepatitis C patients for decades, they have gained a good understanding of how the chronic disease affects people. But the virus itself remains mysterious in many ways.

“We know a lot about the disease itself—its symptoms, how it progresses and those sorts of things,” says Pathology Chair Nelson Fausto. “What we do not know are the real mechanisms through which the virus affects the liver and the immune system.”

Gretch and his colleagues are studying why the virus seems to act differently in different patients—those who get advanced liver disease, for instance, compared to those who carry the infection for years without major liver problems. 

In all chronic hepatitis C patients, the virus mutates very rapidly to adapt to the host’s immune system. But one out of every five people eventually reaches a point where their immune system stops affecting the virus at all. Like an escaping criminal fleeing from the law, the virus changes its disguise over and over again until it blends in perfectly and stays hidden from the immune system. The virus then quits mutating and becomes a “major variant.”

“At that point, the virus has adapted to become the best variant for that particular host,” Gretch explains. “In that 20 percent of cases, it goes bad for the host.”

Learning how the virus adapts to the point where it drops off the radar of the immune system may help scientists determine how to disrupt that process, and perhaps delay or even prevent the onset of advanced liver disease.

One significant difference between hepatitis C virus and its relatives is the lack of a vaccine—both hepatitis A and B can be prevented by protective vaccines. In fact, it was UW Geneticist Ben Hall who created a method in which yeast cells could be used as tiny biochemical “factories” for the replication of hepatitis B vaccine .