But this remarkably successful approach has several drawbacks. Of the six distinct genotypes of the hepatitis C virus, genotypes 2 and 3 are the most responsive, with a cure rate of about 80%. But genotype 1, which accounts for 70% of cases in the United States and northern Europe, is more resistant. Moreover, many people don’t tolerate the treatment well. Interferon is usually described as causing “flulike” symptoms, and they can persist for the year it takes to achieve a cure. “Imagine having flu for a year,” says virologist Earl Brown of the University of Ottawa.
Another daunting obstacle is the expense of the therapy, which costs between $15,000 and $20,000 a year. While that may not be prohibitive for some patients in the West, it sharply limits access in the developing world, where the virus continues to spread through a contaminated blood supply and infected needles. In one tragic instance in Libya, hundreds of children in the same hospital were infected with both HIV and HCV through the re-use of improperly sterilized needles. Even more disturbing, some 15% of the Egyptian population, and half of those older than age 50—more than 5 million people—are thought to be chronically infected with type 4 hepatitis C, as the result of contaminated needles used during a massive antischistosomiasis campaign in the mid-1960s.
Though it wouldn’t help those already infected, a vaccine could slow the spread of hepatitis C and perhaps eventually eliminate HCV as a threat to public health. The vaccine for hepatitis B, introduced in 1982, has greatly reduced the prevalence of that disease. But the protean hepatitis C virus presents special challenges. Once one of the six genotypes establishes a chronic infection in a human host, it keeps mutating, producing what scientists call quasi-species, a swarm of strains that try to outwit the immune system.
Not all portions of the viral genome are equally variable, however. Natural selection has kept some parts quite stable, but others mutate wildly. One such hypervariable region is found in protein E2, part of the envelope around the virus. To study that region and to track the evolution of hepatitis C in a human host, Earl Brown and Yu-Wen Hu of the University of Ottawa have repeatedly tested a patient who, in the beginning, had the virus in his blood but had not yet developed antibodies, which typically show up only after about seven weeks of infection.
Brown and Hu discovered that after the acute phase of the infection, the patient’s immune system had cleared about 95% of the virus. But the remaining 5%, a swarm of viral strains with similar surface proteins, produced a chronic infection. Over time, the surface proteins diverged more and more from those of the original strains, particularly in the hypervariable region of the E2 protein.
Normally, immune cells track down and destroy invading bacteria and virus-infected cells by recognizing them as alien and therefore dangerous. The immune cells “remember” what a particular infection looks like so they can attack if it enters the host again. But with hepatitis C, that doesn’t always happen. Brown and Hu found that in this patient, as viral strains mutated, they came to resemble the host’s own immune proteins and were able to hide from the patient’s immune system. So the body left them alone, and the chronic infection took hold. A Novartis (formerly Chiron) vaccine has been effective in protecting chimpanzees from the disease and was recently studied in a Phase 1 clinical trial at St. Louis University. If such a vaccine shows promise, scientists will need to vaccinate people in high-risk populations—for example, large numbers of intravenous drug users—to see whether they develop hepatitis C less often than do those in a control group.
If this or another vaccine proves safe and effective, it could have its greatest impact in countries of the developing world, particularly in Africa and Asia. But even in the West, and regardless of how soon a vaccine arrives, the impact of the disease will be felt for years to come. People who may have received a blood transfusion before 1992 or injected drugs once at a party 30 years ago could find themselves facing a sometimes untreatable and possibly fatal condition they never knew they had. How much more suffering this rising wave of disease will inflict is still unknown. Two decades of scientific progress has put hepatitis C on the ropes, but the fight continues. 
 Dossier
1. “Epidemiology of Hepatitis C Virus (HCV) Infection,” by Theodore Sy and M. Mazen Jamal, International Journal of Medical Sciences, April 2006. An overview of the virus’s worldwide distribution and its various subtypes, as well as a cogent discussion of the risk factors associated with spread of the disease.
2. “Immunoglobulin mimicry by hepatitis C virus envelope protein E2,” by Yu-Wen Hu et al., Virology, Jan. 12, 2005. This article presents a novel way of understanding how hepatitis C infects: Through a process called molecular mimicry, the virus tricks the immune system by producing proteins that resemble human immune chemicals.
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