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Peginterferon alfa-2a + ribavirin is a combination therapy formerly used as the standard of care for chronic hepatitis C virus (HCV) infection. The regimen consists of peginterferon alfa-2a, a pegylated recombinant interferon, and ribavirin, a synthetic guanosine analog. Peginterferon alfa-2a binds to the cell surface interferon-alpha receptors (IFNAR1 and IFNAR2), activating the JAK-STAT signaling pathway and inducing the expression of interferon-stimulated genes that establish an antiviral state. Ribavirin is a broad-spectrum antiviral that likely exerts its effects through multiple mechanisms, including the inhibition of viral RNA-dependent RNA polymerase, induction of lethal mutagenesis in the viral genome, and inhibition of host inosine monophosphate dehydrogenase (IMPDH), which depletes intracellular guanosine triphosphate pools. While highly effective compared to non-pegylated interferon, this combination has largely been replaced by direct-acting antiviral (DAA) regimens due to superior efficacy and a more favorable side-effect profile.
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