S-adenosyl-methionine and betaine improve early virological response in chronic hepatitis C patients with previous nonresponse

Abstract

Background/Aims: Treatment of chronic hepatitis C (CHC) with pegylated interferon a (pegIFNa) and ribavirin results in a sustained response in approximately half of patients. Viral interference with IFNa signal transduction through the Jak-STAT pathway might be an important factor underlying treatment failure. S-adenosyl-L-methionine (SAMe) and betaine potentiate IFNa signaling in cultured cells that express hepatitis C virus (HCV) proteins, and enhance the inhibitory effect of IFNa on HCV replicons. We have performed a clinical study with the aim to evaluate efficacy and safety of the addition of SAMe and betaine to treatment of CHC with pegIFNa/ribavirin. Methods: In this open-label pilot study, 29 patients with CHC who failed previous therapy with (peg)IFNα/ribavirin were treated with SAMe, betaine, pegIFNa2b and ribavirin. Treatment duration was 6 or 12 months, depending on genotype, and the protocol comprised a stopping rule at week 12 if early virological response (EVR) was not achieved. Virological and biochemical response and safety were assessed throughout the treatment. Results: 29 patients were enrolled and treated according to the study protocol. 79% of the patients were infected with genotype 1, 72% had advanced fibrosis, 76% had previously received pegIFNα/ribavirin, and only 14% achieved EVR to the previous treatment. When treated with the study medications, 17 patients (59%) showed an EVR, only 3 (10%) however achieved a sustained virological response (SVR). SAMe and betaine were found to be safe when used with pegIFNa/ribavirin. Conclusion: The addition of SAMe and betaine to pegIFNα/ribavirin improves early virological response in CHC. Trial Registration: ClinicalTrials.gov NCT00310336. © 2010 Filipowicz et al.