Hepatitis C Treatments

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At the 2012 meeting of the American Association for the Study of Liver Disease in Boston, the results of many trials of new drugs were presented that suggest that it soon may be possible to eradicate hepatitis C virus in almost all infected patients with fewer side effects from drugs and with shorter durations of treatment. The prevention of infection with hepatitis C virus ultimately will require the development of a vaccine to prevent spread of infection; however, the development of a vaccine has been difficult to realize.

Chronic infection with hepatitis C virus is a serious problem. Hepatitis C virus will become a chronic infection in up to 85% of persons infected with the virus. Although the number of new cases of chronic infection with hepatitis C virus has decreased from a high of 200,000 to 7,000 yearly, over the past 10 to 15 years a large pool of chronically infected patients--approximately three million in the U.S.--has developed that needs treatment. Chronic infection leads to cirrhosis of the liver and ultimately to failure of the liver, liver cancer, and life-threatening gastrointestinal bleeding. At these later stages, the only effective treatment has been transplantation of the liver, and hepatitis C virus has become the leading reason for transplantation of the liver in the U.S.

Treatment of chronic hepatitis C virus until now has utilized two types of drugs in combination. One type, interferon, targets an infected person's immune system, stimulating the immune system to attack the virus. The second type of drug, ribavirin (Rebetol, Copegus), interferes with the production of the ribonucleic acid (RNA) that makes up the genetic material of hepatitis C virus. The genetic material of hepatitis C virus is responsible for taking over the infected human cells and directing the cells to produce more virus, at the same time interfering with normal function of the cells. If the genetic material cannot be reproduced, no new virus forms, and the spread of virus to other cells in the body is halted. Unfortunately, however, existing virus remains. (The patient still is infected.)

There have been several problems with combination treatment with interferon and ribavirin. Treatment is effective in no more than 50% of patients who are eligible for treatment, and many patients have not been eligible for treatment due to concerns about side effects. There are many subgroups of patients for whom treatment is not very effective, for example, patients with cirrhosis. Both interferon and ribavirin target systems in the body that are important to everyday health--the immune system and the production of new cells (which is the same system that hepatitis C virus uses to reproduce in the body). As a result, serious, even life-threatening side effects have occurred with treatment. Finally, treatment frequently has required 24 to 48 weeks.

The types of drugs available for treating chronic hepatitis C virus are undergoing a radical change. The genetic material of hepatitis C virus (its RNA) has been sequenced, and most of the virus' genes are now known. Some genes direct the manufacture of enzymes that are crucial to the production of new hepatitis C virus. Others are crucial for production of new hepatitis C virus, but their exact functions are unknown. Knowing the nature of the hepatitis C virus genetic material and its products, it has been possible to develop drugs that target portions of the genetic material or its products and prevent their actions. These drugs are referred to as direct acting anti-viral drugs. The newer drugs target systems that are unique to hepatitis C virus, in contrast to interferon and ribavirin that target systems that are important to everyday health as well as to production of new hepatitis C virus. This shift in focus of treatment to systems that are necessary for survival of the virus, but unimportant to patients results in fewer side effects. In addition, it turns out that the direct acting antiviral drugs are much more effective in eradicating hepatitis C virus - in upwards of 85% of patients - in even those patients who have had poor responses to interferon and ribavirin. There are also hints that treatment is likely to be shorter.

Drugs for treating hepatitis C of a second type, referred to as host-targeted agents, also are being developed. These drugs target proteins that are part of healthy liver cells' machinery but are used by hepatitis C virus to survive and reproduce. It is possible to prevent the virus from using the liver cells' machinery without seriously affecting the health of the liver cell.

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