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

PLoS One. 2010 Nov 8;5(11):e15492. doi: 10.1371/journal.pone.0015492.

Abstract

Background/aims: Treatment 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.

Methods: In 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.

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 pegIFNα/ribavirin.

Conclusion: The addition of SAMe and betaine to pegIFNα/ribavirin improves early virological response in CHC.

Trial registration: ClinicalTrials.gov NCT00310336.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use
  • Arthralgia / chemically induced
  • Betaine / adverse effects
  • Betaine / therapeutic use*
  • Diarrhea / chemically induced
  • Drug Therapy, Combination
  • Fatigue / chemically induced
  • Female
  • Gastrointestinal Agents / adverse effects
  • Gastrointestinal Agents / therapeutic use
  • Headache / chemically induced
  • Hepacivirus / drug effects*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use
  • Male
  • Middle Aged
  • Pilot Projects
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use
  • Prospective Studies
  • Recombinant Proteins
  • Ribavirin / adverse effects
  • Ribavirin / therapeutic use
  • S-Adenosylmethionine / adverse effects
  • S-Adenosylmethionine / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Gastrointestinal Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Betaine
  • Polyethylene Glycols
  • Ribavirin
  • S-Adenosylmethionine
  • peginterferon alfa-2a

Associated data

  • ClinicalTrials.gov/NCT00310336