By Peter Jaret CONSUMER HEALTH INTERACTIVEBelow: • New and more effective treatments • New ways to study hepatitis C • More accurate diagnostic tests • A vaccine against hepatitis C • Staying informed in a fast-changing field

It has been less than 20 years since the hepatitis C virus was first identified. In that time, an extraordinary amount of progress has been made in the fight against this virus. Still, much needs to be done. Improved diagnostic tests are needed to identify people infected with HCV more precisely and less expensively than is possible today. Better ways to prevent transmission are urgently needed. With an astonishing 3 percent of the world's population infected with HCV, the most intense research is being done in the area of treatment. Current treatments eliminate the virus in only a little more than half of all patients. The drugs also have unwanted side effects that make it difficult or impossible for some patients to take them. In all these areas, rapid progress is being made. Here’s an overview from several fronts in the battle against HCV: New and more effective treatments Intense research efforts around the world are focused on developing new and more effective treatments to eliminate or control the hepatitis C virus. Scientists are improving existing drugs in significant ways. The development of pegylated interferon, or peginterferon, has significantly increased interferon's effectiveness. By combining peginterferon with ribavirin, doctors are achieving even better results. Two new versions of ribavirin, called viramidine and levovirin, are currently being evaluated for possible approval. Both are hoped to be more effective in fighting the virus and to trigger fewer side effects, including anemia, than the original ribavirin. Meanwhile, entirely new drugs are also being developed to fight HCV. Researchers hope to use the same model that has proved so successful in developing HIV/AIDS therapies -- targeting enzymes that the virus needs to reproduce. The specific drugs that fight HIV don't work against HCV, because the two viruses use different kinds of enzymes, but the same strategies are likely to work in conquering them. The three most likely targets include three different classes of enzymes: proteases, helicases, and polymerases. Advances are being made against all three. For example, in 2003, researchers announced the identification of a protease enzyme that HCV uses to evade the immune system. The enzyme, labeled NS3/4A, inhibits a key immune system molecule that regulates interferon. The scientists used a protease inhibitor that prevented the virus from making NS3/4A. The experimental drug restored the immune system's ability to respond to the virus. "Now that we know NS3/4 inhibition essentially restores the host's immune response to the virus, we can assess hepatitis drug candidates for this ability as well," says Michael Gale Jr., PhD, of the University of Texas Southwestern Medical Center at Dallas, on behalf of the National Institute for Allergy and Infectious Diseases. In other news, experts report encouraging findings from drugs called antisense oligonucleotides, which block a virus's ability to reproduce. One candidate drug, called ISIS 14803, dramatically reduced HCV levels in patients in a small study reported in 2002. Studies of the experimental medication are ongoing. Extensive testing remains to be done before these and other new antiviral drugs are approved. Still, the fact that so many are in the pipeline is encouraging, experts say. As new drugs become available, doctors will be able to create "cocktails" of treatments, much as they do for HIV-infected patients today. By individualizing therapy, doctors will be able to treat patients more effectively and with fewer side effects. New ways to study hepatitis C Although HCV grows quickly in the human liver, researchers have struggled to find ways to grow the virus in the laboratory. Recently, scientists have developed strains of mice that can be infected with HCV, an advance that should help speed progress in understanding the virus and developing treatments. The ultimate goal is to create tissue cultures for hepatitis C -- living cells that can be infected with the virus in the laboratory. Tissue cultures would make it possible to rapidly test new drug candidates to see if they work against the virus. More accurate diagnostic tests Although existing tests to detect and measure HCV are highly sensitive and specific, they are not perfect. In some cases the tests fail to detect infections (false negatives). In other cases they show positive readings in people not infected, or in people whose bodies have actually eliminated the virus (false positives). Tests that measure the amount of virus in the blood, or viral load, vary widely in quality. Researchers are working on developing more reliable tests that would reduce false negatives and false positives. Another goal is to develop less expensive tests, for use in poorer countries, where cost can make testing prohibitive. A vaccine against hepatitis C The transmission of HCV through blood transfusions and organ transplants has been largely stopped, thanks to increasingly sophisticated screening tests. Now more must be done to prevent its spread among drug users. Needle exchange programs and counseling on safe methods to handle syringes could help. Ultimately, the gold standard for disease prevention is a vaccine. Vaccines "prime" the immune system to detect and destroy invading germs before they can gain a foothold. Some vaccines can even be used to treat people already infected with a virus by boosting their immune response. Unfortunately, experts are still far from developing a hepatitis C vaccine. The biggest challenge is the fact that hepatitis C virus is constantly changing its shape to elude immune detection. For this reason a vaccine that protects against one form of the virus may not protect against others. Still, the scientific community is making progress in identifying stable regions of the virus that do not change, and is exploring a variety of new approaches for developing vaccines. Staying informed in a fast-changing field The swift progress being made on many fronts offers encouragement to everyone infected with HCV. But rapid developments in medicine can also cause confusion and frustration. Preliminary results often make headlines years before new drugs are available. Popular articles may highlight positive results from studies and then fail to follow up when subsequent tests show problems with a new drug or treatment. Sorting through all the information in a fast-changing field like HCV research can be daunting. Two strategies can help you stay abreast of new developments without becoming overwhelmed: First, find a few reliable sources of information and stick with them. Web sites sponsored by federal health agencies like the National Institutes of Health are a good place to start, as they are frequently updated and experts carefully screen the information posted. Here are a few recommended sites: The National Institute for Allergy and Infectious Diseases: http://www.niaid.nih.gov/dmid/hepatitis/ National Institute of Diabetes and Digestive and Kidney Diseases http://www.digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/index.htm National Center for Complementary and Alternative Medicine http://www.nccam.nih.gov/health/hepatitisc/ Second, talk to your doctor. Most doctors want patients to be informed and to ask questions. What's more, your doctor can help you evaluate new findings and put them in the context of other research on hepatitis C. -- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.
References Pietschmann, T. Tissue culture and animal models for hepatitis C. Clinical Liver Disease, Feb 2003, pp 23-43
Frick, D.N. Helicases as antiviral drug targets. Drug News Perspectives, July-Aug 2003, pp 355-62
Foy, E. et al. Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science, Apr 17, 2003
Lechmann, M. et al. Vaccine development for hepatitis C. Liver Diseases Section, NIDDK, National Institutes of Health, Seminars in Liver Disease, Medscape
Watson, J. Prospects for hepatitis C virus therapeutics: levovirin and viramidine as improved derivatives of ribavirin. Curr Opin Investig Drugs, May 2002, pp 680-3
HCV Advocate. HCV Reports from the Retrovirus Conference, Apr 2003
HCV Advocate. Bayer Receives Viral Load Test Approval, May 2003
The National Institute for Allergy and Infectious Diseases.
http://www.niaid.nih.gov/dmid/hepatitis/
National Institute of Diabetes and Digestive and Kidney Diseases http://www.digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/index.htm
National Center for Complementary and Alternative Medicine http://www.nccam.nih.gov/health/hepatitisc/
Reviewed by Alexander Monto, MD, a hepatologist at the Veterans Administration Medical Center in San Francisco.
First published October 28, 2003
Last updated August 24, 2007
Copyright © 2003 Consumer Health Interactive
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