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


Prof. Guglielmo Borgia, Dipartimento di Medicina Pubblica e Sicurezza Sociale, Sezione di Malattie Infettive (Ed. 18), University of Naples ‘Federico II’, via S. Pansini, 5, I-80131 Naples, Italy
Tel: +39 0 81 7463083
Fax: +39 0 81 7463190
e-mail: borgia@unina.it


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 <16 μmol/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-IFNα plus ribavirin treatment, while polymorphisms of MTHFR are not.