Homocysteine levels and sustained virological response to pegylated-interferon alpha2b plus ribavirin therapy for chronic hepatitis C: a prospective study

Liver Int. 2009 Feb;29(2):248-52. doi: 10.1111/j.1478-3231.2008.01832.x. Epub 2008 Jul 24.


Background: Chronic hepatitis C affects about 3% of the world's population. Pegylated interferon (IFN) alpha plus ribavirin is the gold standard treatment. Methylenetetrahydrofolate reductase(MTHFR) is a key enzyme in the metabolism of homocysteine. MTHFR gene polymorphisms and high levels of homocysteine are associated with a high degree of steatosis and fibrosis, conditions associated with a low sustained virological response (SVR) rate.

Aims: To evaluate whether MTHFR polymorphisms and homocysteine levels are predictors of the outcome of treatment in 102 prospectively enrolled patients with chronic hepatitis C naive to treatment.

Methods: Patients were treated with pegylated interferon alpha-2b plus ribavirin. All patients underwent blood tests, assessment of homocysteine, vitamin B(12), folate, hepatitis C virus (HCV)-RNA levels, screening for MTHFR gene polymorphisms and liver ultrasound examination.

Results: Homocysteine levels were deranged (>16 micromol/L) in 10.5% of MTHFR wild-type patients vs 40.3% of non-wild-type patients (P=0.015). Homocysteine levels were 14.4 micromol/L in SVR patients and 15.5 micromol/L in non-SVR patients (P=0.049). The SVR rate was 40.0% in MTHFR wild-type patients, 52.0% in heterozygote mutants and 39.3% in homozygote mutants (P=0.467). At logistic regression analysis, genotypes 2 and 3 (odds ratio: 12.328, 95% confidence interval: 3.390-44.837, P=0.0001), homocysteine <16 micromol/L (odds ratio: 3.397, 95% confidence interval: 1.033-11.177, P=0.044) and aspartate aminotransferase (AST) levels <48 U/L (odds ratio: 3.262, 95% confidence interval: 1.125-9.458, P=0.029) were independent predictors of SVR.

Conclusions: In patients with chronic hepatitis C, homocysteine levels are associated with the outcome of pegylated-IFNalpha plus ribavirin treatment, while polymorphisms of MTHFR are not.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Folic Acid / blood
  • Hepacivirus / drug effects*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / metabolism
  • Hepatitis C, Chronic / pathology
  • Homocysteine / blood*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use*
  • Italy
  • Methylenetetrahydrofolate Dehydrogenase (NADP) / genetics
  • Polyethylene Glycols
  • Polymorphism, Genetic
  • Prospective Studies
  • RNA, Viral / blood
  • ROC Curve
  • Recombinant Proteins
  • Ribavirin / pharmacology
  • Ribavirin / therapeutic use*
  • Vitamin B 12 / blood


  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Homocysteine
  • Polyethylene Glycols
  • Ribavirin
  • Folic Acid
  • Methylenetetrahydrofolate Dehydrogenase (NADP)
  • peginterferon alfa-2b
  • Vitamin B 12