Association of Serum Vitamin B12 Levels with Stage of Liver Fibrosis and Treatment Outcome in Patients with Chronic Hepatitis C Virus Genotype 1 Infection

Abstract

Chronic hepatitis C represents a worldwide health problem. In the last years new therapeutic strategies with a very good sustained virological response rate have been developed. These new therapeutic agents are mainly available in the economically developed countries. A problem in the treatment of the CHC is, globally, that the majority of patients is living in countries with health budgets unable to meet such costs. This is why predictors of therapeutic response under classical therapy (IFN und RBV) are still nec-essary. In vitro studies provided evidence for Vitamin B12 to interfere with HCV replication. Thus, we retrospectively analyzed the relationship between serum baseline Vitamin B12 concentrations and clinical data from a total of 116 CHC patients with HCV genotype 1 infection who received an antiviral combination therapy with Peg-IFN-α and RBV. The statistical approach covered uni- and multivariate analyses using logistic regression models. Serum baseline Vitamin B12 concentrations were found to be positively associated with serum transaminase activities (AST, p=0.002, ALT, p=0.04), baseline viral load (p<0.0001), stage of fibrosis (p=0.0001) and the favorable IFN-λ3 rs12979860 C allele (p=0.04). To the contrary, an inverse relationship was found be-tween serum baseline Vitamin B12 concentrations and RVR and SVR rates (p=0.001 and p<0.001, respectively). By using a ROC analysis we defined a cut-off level for baseline serum Vitamin B12 of 570 ng/L. Patients with serum baseline Vitamin B12 concentrations below this level achieved an SVR rate of 59% compared to patients with higher Vitamin B12 concentrations achieving an SVR rate of only 10% (OR of 13.4 (CI: 4.3-41.9, p<0.0001). Notably, patients with serum baseline Vitamin B12 concentrations below the cut-off and a favorable IFN-λ3 rs12979860 CC genotype featured SVR rates of 80%, while patients with higher concentrations and carrying the unfavorable T allele reached a 7% SVR rate only (OR of 54 (CI: 9.9-293.4, p<0.0001)). Our data suggest that serum baseline Vitamin B12 concentration may be used as a non-invasive marker for the CHC-related fibrosis. In addition, it might be taken as a useful predictor for therapy responsiveness by identifying patients with high chances to benefit from an antiviral Peg-IFN-α and Ribavirin combination therapy.