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This combination therapy was evaluated in a Phase 2/3 open-label pilot study (NCT00310336) conducted by the University Hospital, Basel, for the treatment of chronic hepatitis C in patients who failed previous interferon-based therapy. The regimen consists of pegylated interferon alpha-2b, a biologic that activates the Jak-STAT signaling pathway to induce an antiviral state, and ribavirin, a nucleoside analog that interferes with viral RNA synthesis. To enhance the efficacy of this standard-of-care combination, S-adenosyl-L-methionine (AdoMet) and betaine were added as methyl donors. The rationale for this addition is that the hepatitis C virus (HCV) inhibits interferon signaling by impairing STAT1 methylation; providing AdoMet and betaine is intended to restore STAT1 methylation, thereby improving the virological response in previously non-responsive patients.
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