Larger gains sought in hepatitis C treatment
■ Despite some success, the viral disease is still the most common chronic bloodborne infection in the United States.
By Susan J. Landers — Posted Feb. 14, 2005
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Washington -- There are still gains to be made in the treatment of hepatitis C, and a recent congressional hearing on the disease as well as a National Institutes of Health workshop to discuss a vaccine to fight this liver-ravaging condition hold out hope for more progress.
"In the last 10 years, we've quadrupled the treatment response rate," said Michael Bernstein, MD, director of the Hepatitis Clinic at Coney Island Hospital in Brooklyn, N.Y.
There is now an overall success rate of about 55%, researchers say. Treatment with long-acting interferon or a combination of interferon and other antiviral drugs has made the difference.
"We are still, however, left with those unfortunate 45% who don't respond," said Adrian M. DiBisceglie, MD, chief of hepatology at Saint Louis University School of Medicine.
And that's a lot of people. Hepatitis C is the most common chronic bloodborne infection in the United States. About 4 million Americans are chronically infected, and most are not even aware of this threat to their health.
Primary care physicians have a major role to play in diagnosing the infection, so that those who can benefit from treatment will receive it in time to prevent extensive liver damage, Dr. Bernstein said. The AMA and the Centers for Disease Control and Prevention have collaborated on materials targeted to doctors and patients to help with early diagnosis.
"Hepatitis C was only identified 15 years ago, so we still have much to learn about this disease," said Rep. Tom Davis, (R, Va.), chair of the House Committee on Government Reform. Davis held a hearing on hepatitis C Dec. 14, 2004.
An NIH workshop on vaccine development was scheduled for Feb. 1 and 2.
Early warning system
Hepatitis C infection often presents no warning symptoms, and many people could have unknowingly become infected from intravenous drug use years earlier or from contaminated blood or blood products received before widespread screening for the virus began in the early 1990s.
The virus is sometimes only discovered after a patient exhibits signs of serious liver disease, such as cirrhosis or liver cancer, Davis said.
Still, the forward march of treatment has resulted in substantial gains for many of those infected. "We started out treating patients with hepatitis C in the mid-80s with interferon," Dr. DiBisceglie said. At that stage, no more than 5% to 10% of patients had a sustained virologic response, he added.
Treatment refinements made since then include the use of combination therapy with pegylated interferon and ribavirin that extends the life of interferon, thus allowing it to fight the virus longer.
Today's positive outcomes jump even higher for those infected with one of the less common viral genotypes. For those infected with genotype 2 the success rate is probably 90%, and for genotype 3, it's about 70% to 80%, Dr. Bernstein said.
However, treating genotype 1 infections, the most common of the viral types, has not met with as much success. African-Americans, for whom the cure rate is the lowest, are most frequently infected with this genotype.
But it isn't just infection with genotype 1 that is making the difference in this population, Dr. DiBisceglie said. "Even if you account for genotype, the response rate is less than in whites," he said. While about 40% of whites with the genotype respond to treatment, the level drops to 30% to 40% for African-Americans. Studies are under way to examine the possible reasons for the poorer response rate.
A lesson can be drawn from this conundrum, said Stanley M. Lemon, MD, professor of microbiology and immunology at the University of Texas Medical Branch in Galveston and director of the Hepatitis Research Center there.
That lesson is to include all populations in clinical studies, he said. "If you have selected populations that don't really need to be treated by the drug, you are going to lose valuable information."
Work also has been ongoing to develop an effective vaccine, and some candidates are currently being tested. But the complex nature of the virus presents many obstacles.
"The problem is, like the AIDS virus, the envelope proteins you would likely target mutate very quickly," Dr. Bernstein said, which makes it much more difficult to design a vaccine. In contrast, proteins in hepatitis B, for which a successful vaccine has been developed, are much less variable.
Dr. Lemon finds promise in the development of small molecule antiviral inhibitors, which have been shown to cause a sharp drop in hepatitis C viral levels in a short time. Although studies of one such drug were halted because of high toxicity, others could meet with more success. "The importance of those studies, even if that drug never makes it to market, is that small molecule therapy, antivirals like we have for HIV and herpes, are nearing reality and have incredible potential," Dr. Lemon said.