In the last few weeks there have been several alarming reports of hepatitis A exposure at St. Louis restaurants. A virus transmitted by improper sanitation (typically, failure to wash hands after defecating), hepatitis A is no joke. But you are only sick for a few weeks, and infection is a rare event. By the end of October, a total of 72 cases had been reported in St Louis City and County this year.

I worry far more about another kind of hepatitis, a silent killer called hepatitis C.

Many readers may not be aware that our country is in the midst of an epidemic of this potentially fatal liver disease. Almost 4 million Americans are infected with the hepatitis C virus, most of them without knowing it. Some 9000 people will die this year in the U.S. from liver cancer and chronic liver failure brought on by the virus, and the number is expected to triple in the next decade. In the next few years, the number of annual U.S. deaths caused by hepatitis C is predicted to overtake deaths caused by AIDS.

Hepatitis is inflammation of the liver. There are three common forms. One, called infectious hepatitis or hepatitis A, is transmitted by contact with feces from infected individuals. This is the form apparantly carried by several St. Louis restaurant workers. A second form of hepatitis, called serum hepatitis or hepatitis B, is passed only through the blood. Both cause a brief, intense infection and then are done. Hepatitis A, for example, typically lasts a few weeks.

The third form, hepatitis C, is unlike hepatitis A and B in a very important respect: it causes chronic disease. 90% of people with hepatitis C have it for years, many of them for decades.

All during these long years of infection, damage is being done to the liver. Cells of the immune system called cytotoxic T cells recognize hepatitis C virus proteins on the surface of liver cells, and kill the infected cells. Over the years, many dead liver cells accumulate, and in response the cells around them begin to secrete collagen and other proteins to cover the mess. This eventually produces protein fibers interlacing the liver, fibers which disrupt the flow of materials through the liver's many internal passages. Imagine dropping bricks and rubble on a highway -- it gets more and more difficult for traffic to move as the rubble accumulates.

If this fibrosis progresses far enough, it results in complete blockage, cirrhosis, a serious condition which may induce fatal liver failure, and which often induces primary liver cancer. About 20% of patients develop cirrhosis within 20 years of infection. Until then, few experience any symptoms at all. In all this time, individuals are fully infectious.

Luckily, hepatitis C is a very difficult virus to transmit. Direct blood contact is the only known path of direct transmission. Sexual transmission does not seem likely, although the possibility is still being investigated. Married partners of infected individuals rarely get the virus, and its incidence among promiscuous gay men is no higher than among the population at large.

Why not move vigorously to produce a vaccine directed against hepatitis C? This turns out to be particularly difficult for this virus. Infected individuals produce antibodies directed against the virus, but the antibodies don't protect them. Hepatitis C virus evades our antibody defenses by high mutation rates, just as the AIDS virus does. By the time antibodies are being produced against one version of the virus, some of the viruses have already mutated to a different form that the antibody does not recognize. Like chasing a burglar who is constantly changing his disguise, the antibodies never learn to recognize the newest version of the virus.

Attempts to find a hepatitis C vaccine are instead focused on the part of our immune system that attacks infected liver cells. Unlike the ineffective antibody defense, our bodies' cytotoxic T cells clearly are able to detect and attack cells carrying hepatitis C proteins. A vaccine that stimulates these cytotoxic T cells might enable them to eliminate all infected cells at the start of an infection, stopping the disease in its tracks before it got started. A serious effort is being made to develop such a vaccine.

It doesn't look like an effective vaccine is going to be available anytime soon. In the meantime, public concern is beginning to be felt in Washington. The NIH has increased funding for hepatitis C research to $33.6 million for next year. However, this is a paltry amount compared to the $1.8 billion to be spent on AIDS virus research. As the death rates from hepatitis C exceed those for AIDS in the next few years, we can hope NIH will further intensify its efforts.

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