Chronic Hepatitis C: Current Disease Management

Basic Research

A major focus of hepatitis C research is developing a tissue culture system that will enable researchers to study HCV outside the human body. Animal models and molecular approaches to the study of HCV are also important. Understanding how the virus replicates and how it injures cells would be helpful in developing a means of controlling the virus and to screen for new drugs that would block the virus.

Diagnostic Tests

Reliable and inexpensive assays for measuring HCV RNA and antigens in the blood and liver are needed. Although current tests for anti-HCV are quite sensitive, a small percentage of patients with hepatitis C test negative for anti-HCV (false negative reaction), and a percentage of patients who test positive are not infected (false positive reaction). Also, there are patients who have resolved the infection but still test positive for anti-HCV. Convenient tests to measure HCV in serum and to detect HCV antigens in liver tissue would be helpful.

New Treatments

New therapies are needed for hepatitis C. Agents being evaluated include

• Other forms of alpha interferon.
• Beta interferon.
• Thymosin.
• Amantadine.
• Nucleoside analogs, including ribavirin.
• Combinations of alpha interferon and ribavirin.

Most information suggests that all forms of alpha and beta interferon give similar results, although the optimal dose for each preparation may be different. Nucleoside analogs are the major forms of antiviral medications used to treat AIDS and herpes virus infections. Most nucleoside analogs such as AZT and acyclovir act mostly on DNA viruses. Among nucleoside analogs currently being used, ribavirin has been shown to be potentially helpful in hepatitis C. Alone, ribavirin has limited efficacy. It lowers aminotransferases in 30 to 50 percent of patients, but it does not reduce the amount of virus, and virtually all patients relapse when treatment is ended. A more promising approach to therapy is the combination of alpha interferon and ribavirin, which in small studies appears to lead to a higher long-term response rate than alpha interferon alone.

Researchers are actively trying to develop new antiviral agents for hepatitis C. Most interesting will be specific inhibitors of HCV-derived enzymes such as protease and polymerase inhibitors. Molecular approaches to treating hepatitis C are also being investigated, such as using antisense oligonucleotides, which are small complementary segments of DNA that bind to viral RNA and inhibit viral replication. All of these approaches remain experimental and have not been applied to humans. The serious nature and the frequency of hepatitis C in the population make the search for new therapies of prime importance.

Prevention

At present, the only means of preventing new cases of hepatitis C are to screen the blood supply, encourage health professionals to take blood and body fluid precautions, and inform people about high-risk behaviors. Programs to promote needle exchange offer some hope in decreasing hepatitis C spread among injection drug users. Vaccines and immune globulin products do not exist for hepatitis C, and development in the near future seems unlikely because these products would require antibodies to all the genotypes and variants of hepatitis C. Nevertheless, advances in immunology and innovative approaches to immunization make it likely that some form of vaccine will eventually be developed for hepatitis C.

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