S-Adenosyl-Methionine and Betaine Improve Early Virological Response in Chronic Hepatitis C Patients with Previous Nonresponse

Magdalena Filipowicz,Francois H T Duong,Markus H Heim,Luigi Terracciano,Christine Bernsmeier,John E Tavis

doi:10.1371/journal.pone.0015492

Magdalena Filipowicz, Francois H T Duong + Show 4 more

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https://doi.org/10.1371/journal.pone.0015492

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Journal: PloS one	Publication Date: Nov 8, 2010
Citations: 31	License type: CC BY 4.0

Affiliation: University Hospital of Basel

Abstract

Background/AimsTreatment of chronic hepatitis C (CHC) with pegylated interferon α (pegIFNα) and ribavirin results in a sustained response in approximately half of patients. Viral interference with IFNα signal transduction through the Jak-STAT pathway might be an important factor underlying treatment failure. S-adenosyl-L-methionine (SAMe) and betaine potentiate IFNα signaling in cultured cells that express hepatitis C virus (HCV) proteins, and enhance the inhibitory effect of IFNα 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 pegIFNα/ribavirin.MethodsIn this open-label pilot study, 29 patients with CHC who failed previous therapy with (peg)IFNα/ribavirin were treated with SAMe, betaine, pegIFNα2b 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.Results29 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 pegIFNα/ribavirin.ConclusionThe addition of SAMe and betaine to pegIFNα/ribavirin improves early virological response in CHC.Trial RegistrationClinicalTrials.gov NCT00310336

Highlights

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide [1]
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 pegylated IFNa (pegIFNa)/ribavirin, and only 14% achieved early virological response (EVR) to the previous treatment
SAMe and betaine were found to be safe when used with pegIFNa/ribavirin

Summary

Introduction

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide [1]. Chronic hepatitis C (CHC) may lead to liver cirrhosis and hepatocellular carcinoma. Type I interferons (IFNs), IFNa and IFNb, are crucial and potent components of the early host response against virus infection [2] and recombinant (pegylated) IFNa2a and IFNa2b are widely used for the treatment of CHC and chronic hepatitis B. The current standard treatment of CHC with pegylated IFNa (pegIFNa) and ribavirin leads to cure in about 50% of patients [3,4]. The cause of treatment failure in the remaining half of the patients is poorly understood. Viral interference with IFNa signal transduction from the cell surface to the nucleus is considered an important mechanism behind ineffective treatment responses

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Results

Conclusion