Homocysteine levels and sustained virological response to pegylated-interferon α2b plus ribavirin therapy for chronic hepatitis C: a prospective study

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. 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. 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. Homocysteine levels were deranged (> 16 mu mol/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 mu mol/L in SVR patients and 15.5 mu mol/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 mu mol/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. In patients with chronic hepatitis C, homocysteine levels are associated with the outcome of pegylated-IFN alpha plus ribavirin treatment, while polymorphisms of MTHFR are not.