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

Background: Chronic hepatitis C affects about 3% of the world's population. Pegylated interferon (IFN) α 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 α-2b plus ribavirin. All patients underwent blood tests, assessment of homocysteine, vitamin B₁₂, folate, hepatitis C virus (HCV)-RNA levels, screening for MTHFR gene polymorphisms and liver ultrasound examination. Results: Homocysteine levels were deranged (>16 μmol/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 μmol/L in SVR patients and 15.5 μmol/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