Update on Hepatitis C Treatment

, Clinical Instructor, UCLA School of Medicine, Los Angeles, California, and , Medical Director, Liver Transplantation, Cedars-Sinai Medical Center, Associate Professor of Medicine, UCLA School of Medicine, Los Angeles, California

Disclosures

February 15, 2001

In This Article

Pegylated Interferon

Pharmacokinetic studies have provided a rationale for enhanced IFN dosing. The initial decline in serum HCV RNA levels seen after a single dose of IFN therapy is believed to reflect a direct antiviral effect, whereas the subsequent and more delayed decline in HCV RNA levels is due to destruction of infected hepatocytes.[22] An important limitation of the antiviral effect of standard IFN dosing is the rapid decline in circulating drug level with thrice-weekly administration. The short half-life of the drug and the rapid production of HCV virions diminish the efficacy of standard IFN therapy. In an effort to achieve more stable and efficacious IFN activity, pegylated formulations have been developed.

The production of a pegylated IFN involves the addition of a nontoxic long-acting formulation of interferon using the drug delivery system of pegylation. Polyethylene glycol molecules are added to IFN-alfa 2a (Pegasys, Hoffmann-La Roche) and IFN-alfa 2b (PEG-Intron, Schering-Plough). Pegylation is already used in the delivery of other drugs. Its attachment to IFN-alfa permits once-weekly dosing.

In a recent report, Zeuzem and colleagues[23] indicate that at week 72, the SR was 39% after 48 weeks of therapy at a dose of 180 mcg with pegylated IFN alfa-2a compared with a 19% SR in control patients. Drug discontinuation in these treatment-naive patients and frequency of dose reduction were similar in the 2 treatment arms. Heathcote and colleagues[24] have also reported on the use of pegylated IFN alfa-2a in a controlled trial in cirrhotic patients. SR was 30% following 48 weeks of therapy with 180 mcg, compared with 8% for patients treated with standard alfa IFN, again without a significant increase in side effects with the pegylated product.

Trepo and colleagues[25] have also reported, in abstract form, initial studies with pegylated IFN-alfa 2b. Virologic SR for the unmodified IFN-alfa 2b (3 million units, thrice weekly for 48 weeks) was 12%, whereas the SR for the pegylated IFN-alfa 2b was 18%, 25%, and 23% with 0.5 mcg/kg, 1.0 mcg/kg, and 1.5 mcg/kg, respectively, administered weekly in treatment-naive patients.

As with standard IFN-alfa monotherapy, ribavirin may augment response rates when combined with the pegylated IFNs.[26,27] Recent trials will help evaluate further the role of ribavirin in augmenting the efficacy of pegylated IFN (see Figure).

Initial antiviral therapy against hepatitis C virus.*
* Abbreviations: IFN = interferon; CSN = consensus interferon; IFN/RIB = interferon + ribavirin; PEG = pegylated interferon; PEG/RIB = pegylated interferon + ribavirin.

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