Which medications in the drug class Antiviral agents are used in the treatment of Pediatric Hepatitis C?

Updated: May 10, 2019
  • Author: Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP; Chief Editor: Russell W Steele, MD  more...
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Answer

Antiviral agents

Interferons (IFNs) are synthetically derived from a class of proteins that is produced and released by cells after viral invasion. They stimulate the production of another protein that inhibits viral replication. The nucleoside analogue ribavirin has some antiviral activity against hepatitis C virus, although improvements are not typically sustained after monotherapy is discontinued. However, the use of ribavirin in combination with IFN alpha is more effective than either drug alone and provides sustained responses.

Ribavirin (Rebetol, Copegus)

Ribavirin inhibits viral replication by inhibiting DNA and RNA synthesis. It is administered as combination therapy with IFN alpha-2b. Ribavirin may potentiate the effects of IFN alpha, improving sustained-response rates with HCV.

Peginterferon alfa-2a (Pegasys)

Pegylated IFN is used in combination with ribavirin to treat patients with chronic HCV infection who have compensated liver disease and have not previously received IFN alfa. Pegasys consists of IFN alfa-2a attached to a 40-kd branched PEG molecule (alfa-2b has a smaller 12-kd PEG molecule and is made from IFN alpha-2b). It is predominantly metabolized by the liver.

Several recent small clinical trials have shown that PEG-IFN used in combination with ribavirin is superior to standard IFN therapy. Which populations these recommendations can be extended to (the trials involved mostly HIV/HCV coinfected individuals) and whether alfa-2a is better than alfa-2b or vice versa is not yet clear.

It is indicated as part of a combination regimen with other HCV antiviral drugs in children aged >5 y with compensated liver disease.

Peginterferon alfa-2b (PEG Intron)

E coli recombinant product. Used to treat chronic hepatitis C in patients not previously treated with interferon alfa who have compensated liver disease. Exert cellular activities by binding to specific membrane receptors on cell surface, which in turn may suppress cell proliferation and may enhance phagocytic activity of macrophages. May also increase cytotoxicity of lymphocytes for target cells, and inhibit virus replication in virus-infected cells.

It is indicated combination with ribavirin in children aged ≥3-17 y with compensated liver disease.

Interferon alfa-2b (Intron A)

INF alfa-2b is a protein product manufactured with recombinant DNA technology. Its mechanism of antiviral activity is not clearly understood. However, modulation of host immune responses enhances cytolytic T-cell activity, stimulates natural killer cell activity, and amplifies HLA class I protein on infected cells. Its direct antiviral activity activates viral ribonucleases, inhibits viral entry to cells, and inhibits viral replication. A direct antifibrotic effect has been postulated.

Prior to initiation of therapy, perform tests to quantitate peripheral blood hemoglobin, platelets, granulocytes, hairy cells, and bone marrow hairy cells; monitor periodically (eg, monthly) during treatment to determine response to treatment; if patient does not respond within 4 mo, discontinue treatment. If a response occurs (as measured by clinical improvement, a reduction in HCV viral load, or histologic improvement on liver biopsy), continue treatment until no further improvement is observed.

Whether continued treatment after that time is beneficial remains unknown. Some studies have found some salvage regimens with PEG-IFN to be of benefit.

It is indicated in combination with ribavirin for treatment of chronic hepatitis C in children aged ≥3 y with compensated liver disease previously untreated with alpha interferon therapy and in patients aged ≥18 y who have relapsed following alpha interferon therapy.


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