New Advances in Hepatitis C Research

It has been only several decades 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

The Food and Drug Administration has approved a new two-drug combo named Harvoni, which combines sofosbuvir and another antiviral drug called ledipasvir, which offers a cure for hepatitis C in as little as eight weeks. Patients taking the new drug run a much lower risk of serious side effects associated with the standard treatment for hepatitis C. Unfortunately, the high cost of the medicine means that some patients who need it may not be eligible for it, but it has been hailed as a major breakthrough in hepatitis C treatment.

Scientists are also improving existing drugs in significant ways. The development of pegylated interferon, or peginterferon, significantly increased interferon's effectiveness. By combining peginterferon with ribavirin, doctors are achieving even better results. A new version of ribavirin called viramidine (taribavirin) is under investigation and at least one study has shown that it triggers fewer side effects, including anemia, than the original ribavirin. It has not yet been approved by the Food and Drug Administration, but has shown some promise in clinical trials.

Research on a hepatitis C-specific protease inhibitor called telaprevir also forecasts a new era in treatment. The New England Journal of Medicine reported on a study that showed significant improvement in the chances of being cured when telaprevir was added to the current standard therapy, and treatment took only half the time. Telaprevir is marketed under the names Incivek and Incivo.

Another drug that shows promise in clinical trials is the anti-cholesterol medication fluvastatin. A small study of veterans in 2008 found that fluvastatin may help to temporarily reduce hepatitis C levels. Now researchers will look at combining it with standard therapy in an effort to improve cure rates.

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.

Extensive testing remains to be done before some of these 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 developed strains of mice that can be infected with HCV, an advance that should help speed progress in understanding the virus and developing treatments. And scientists at the University of California, San Diego announced that they had succeeded in developing the first tissue culture of normal human liver cells that can be infected with the virus in the laboratory. This should facilitate more rapid testing of new drug candidates in the future.

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 of Allergy and Infectious Diseases
https://www.niaid.nih.gov/diseases-conditions/hepatitis-research

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.

References

Pietschmann, T. Tissue culture and animal models for hepatitis C. Clinical Liver Disease, 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,pp 680-3.

HCV Advocate. HCV Reports from the Retrovirus Conference.

HCV Advocate. Bayer Receives Viral Load Test Approval.

The National Institute for Allergy and Infectious Diseases. Hepatitis C. http://www.niaid.nih.gov/topics/hepatitis/hepatitisc

McHutchison JG, Manns MP, Longo DL. Definition and management of anemia in patients infected with hepatitis c virus. Liver International. Vol. 26(4): 389-98.

Bader T et al. Fluvastatin inhibits hepatitis C replication in humans. American Journal of Gastroenterology. Vol. 103(6): 1390-92.

Buck M. Direct infection and replication of naturally occurring hepatitis C virus genotypes 1, 2, 3, and 4 in normal human hepatocyte cultures. PLoS One, Vol. 3(7).

Marcellin, P et al. Safety and efficacy of viramidine versus ribavirin in VISER2: Randomized, double-blind study in therapy-nave hepatitis C patients. Journal of Hepatology. October 2009.

McHutchison, JG et al. Telaprevir with peginterferon and ribavirin for chronic HCV Genotype 1 infection. New England Journal of Medicine. April 2009.

Duke Medicine. New Biomarker Predicts Response to Hepatitis C Treatment. August 16, 2009. http://www.dukehealth.org/HealthLibrary/News/new_biomarker_predicts_response_to_hepatitis_c_treatment

National Institute of Allergy and Infectious Diseases. Viral Hepatitis. 2009. http://www.niaid.nih.gov/dmid/hepatitis/

National Institute of Diabetes and Digestive and Kidney Diseases. Chronic Hepatitis C: Current Disease Management. January 2010. http://www.digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/index.htm

National Center for Complementary and Alternative Medicine. CAM and Hepatitis C: A Focus on Herbal Supplements. October 2009. http://www.nccam.nih.gov/health/hepatitisc/

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