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Pegylated interferon in the treatment of chronic hepatitis C virus infection

INTRODUCTION

Pegylated interferon (peginterferon) in combination with ribavirin represents the current standard of care for patients with chronic hepatitis C who are considered to be eligible for treatment. This topic review will summarize clinical trials of peginterferon in the treatment of hepatitis C. General recommendations for care of patients with hepatitis C are provided separately. (See "Treatment of chronic hepatitis C virus infection: Recommendations for adults".)

This topic is also discussed in a guideline issued by the American Association for the Study of Liver Diseases. The AASLD guideline for the diagnosis, management, and treatment of hepatitis C [1], as well as other AASLD guidelines, can be accessed through the AASLD web site at http://www.aasld.org/practiceguidelines/Pages/default.aspx.

RATIONALE FOR PEGYLATION

The attachment of polyethylene glycol to a protein (pegylation) reduces its rate of absorption following subcutaneous injection, reduces renal and cellular clearance, and decreases the immunogenicity of the protein. All of these effects tend to enhance the half-life of the pegylated versus the native protein. On the other hand, pegylation may also interfere with the ability of a protein to bind to its receptor, thereby decreasing its biologic effect. Thus, the true biologic effect of the pegylated protein is determined by the balance of these competing properties [2-6].

The potentially favorable effects of pegylation provide the rationale for the development of pegylated interferons for the treatment of hepatitis C. The higher steady-state concentrations that could be achieved with pegylated interferons were predicted to have favorable therapeutic effects based upon viral kinetic studies, a hypothesis that has been supported by the results of controlled clinical trials [7-10].

Two formulations of pegylated interferon have been developed: peginterferon alfa-2a (Pegasys, Roche Pharmaceuticals), and peginterferon alfa-2b (Peg-Intron, Schering-Plough Corporation). Both are approved for treatment of HCV and are available in combination therapy with ribavirin.
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