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A Good AASLD Meeting Summary

November 25, 2005

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This is a terrific overview article regarding the AASLD meeting. Liz Highleyman did a fantastic job of condensing the key aspects and announcements.

One of the most interesting updates/corrections of known information is the upward measurement of the number of infected persons in the USA. It could be one million more than most commonly estimated.

Hepatitis research reported at liver disease meeting

Liz Highleyman

Treatments for hepatitis B and C continue to improve, with refinements to approved regimens and new experimental agents in the development pipeline, researchers reported at the 56th annual meeting of the American Association for the Study of Liver Diseases, held November 11-15 in San Francisco.

Hepatitis B and C are viral diseases that can cause long-term liver damage including cirrhosis and cancer. The Centers for Disease Control and Prevention estimates that some 75,000 people in the U.S. are newly infected with hepatitis B each year – a number that has declined dramatically since the advent of routine childhood vaccination.

Unlike hepatitis A and B, there is not yet a vaccine for hepatitis C. The National Health and Nutrition Examination Survey found that about 3.9 million people in the U.S. had contracted hepatitis C, but Dr. Brian Edlin from Cornell University presented evidence suggesting this is an underestimate. As a household survey, Edlin said, NHANES does not count several groups that have higher rates of hepatitis C than the general population. These include prisoners (nearly 2 million, with an estimated hepatitis C rate of 32 percent), the homeless (more than 800,000, with an estimated rate of 35 percent), patients in hospitals and nursing homes, and members of the military. Taking these groups together, Edlin estimated that about 1 million more people have hepatitis C than usually reported, for a total of 5 million. Basing public health projections on the lower figure, he warned, "may underestimate the burden of liver disease we will see in coming decades."

Hepatitis C
The hepatitis C virus is spread primarily through contact with blood, and rates are highest among injection drug users. Several studies have shown that sexual transmission between monogamous heterosexual partners is rare, but it appears more common among men who have sex with men and people coinfected with HIV. While outbreaks of sexually transmitted hepatitis C have not been reported in North America, a cluster of more than 200 such cases among gay HIV-positive men in the United Kingdom raises concern.

According to a presentation by Dr. Mark Danta from the Royal Free and University College Medical School in London, a variety of factors related to sexual activity and drug use have contributed to the recent English epidemic. In a case-control study comparing 60 HIV-positive gay men with acute (recently acquired) hepatitis C and 130 matched HIV-positive men without HCV, Danta's team found that the HCV-infected men were significantly more likely to have engaged in unprotected receptive or insertive anal intercourse, fisting, analingus (rimming), use of sex toys, SM, and group sex. Further, the men with hepatitis C were more likely to meet partners in sex clubs, bathhouses, or on the Internet; had more sex partners overall; were more likely to have ever had a sexually transmitted disease; and more often used club drugs including crystal methamphetamine.

While all these factors are linked to higher rates of hepatitis C, Danta said it is "difficult to tease out" how each specifically contributes. He recommended that education about safe sex and drug-sharing practices should be the focus of public health interventions for this population.

At a satellite symposium, HIV specialist Dr. Paul Volberding from the University of California, San Francisco joined several hepatitis experts to discuss similarities and differences between the HIV and HCV viruses and their treatment. Research on hepatitis C is some five to 10 years behind HIV research, Volberding estimated. Hepatitis C researchers are at a disadvantage because HCV cannot be grown in the laboratory, which is important for understanding the virus life cycle and early drug testing (instead, various model systems are used). But patients with hepatitis C enjoy a big advantage: HCV can essentially be eradicated, while HIV persists indefinitely in long-lived memory T-cells.

Current standard treatment for hepatitis C is based on interferon, an injected cytokine (cell messenger chemical) that stimulates the immune response, but future therapies under study directly target HCV. Like current HIV drugs, these new agents will likely be used in combination, since HCV – like HIV – can mutate rapidly and develop drug resistance. But because hepatitis C can be cured in a matter of months or years, there is less concern about long-term side effects such as lipodystrophy.

"This field is getting very lively and will become even more competitive," predicted hepatology researcher Dr. John McHutchinson of Duke University Medical Center in North Carolina.

Indeed, researchers at AASLD presented data on several new candidate hepatitis C drugs. Those furthest along in the pipeline include Idenix Pharmaceuticals' nucleoside analog valopicitabine (NM283) and two HCV protease inhibitors, Shering Plough's SCH503034 and Vertex Pharmaceuticals' VX-950.

Presenting the first data from a phase II trial of valopicitabine, Dr. Christopher O'Brien from the University of Miami reported that 50 percent to 70 percent (depending on dose) of patients with genotype 1 HCV – the hardest type to treat – who did not respond to previous interferon therapy saw an early reduction in HCV viral load after 12 weeks of treatment with the new drug plus pegylated interferon.

"These are promising results, particularly for the many treatment-refractory patients in urgent need of new therapeutic options," O'Brien said.

Dr. Stefan Zeuzem from Germany reported that in a small 14-day study of patients who did not respond to standard treatment with interferon, 60 percent of those receiving the highest dose of SCH503034 three times daily experienced a substantial (at least two logs) reduction in HCV viral load. SCH503034 also showed promising activity when combined with pegylated interferon.

As reported by Dr. Henk Reesink from Amsterdam, in a small early study, all participants with genotype 1 HCV who received VX-950 saw at least a two-log drop in HCV viral load. "As far as I know, this is the most rapid and dramatic response that has been seen with a single agent," he stated.

All three pipeline drugs appear safe, with no serious side effects seen in clinical trials so far. This is reassuring since research on an earlier HCV protease inhibitor, BILN-2061, had to be stopped when it was linked to heart problems in animals. It is too soon to say whether these agents will ultimately produce a cure for hepatitis C (sustained virological response, or continued undetectable HCV viral load six months after the end of treatment). Most experts agree, however, that combinations of antiviral drugs are the wave of the future for hepatitis C therapy.

Posted by Ralph at November 25, 2005 6:16 PM