Urinary nitrite/nitrate concentrations and total antioxidant capacity in patients with chronic hepatitis C in therapy with interferon and ribavirin

In this study we tried to elucidate the role of nitric oxide (NO) in chronic hepatitis C in relation to antioxidant status, since the mechanisms by which hepatitis C virus (HCV) causes cell damage and the factors underlying its resistance to therapy are not well understood. Before and after one and six months of therapy with alpha-interferon and ribavirin, we measured nitrite/nitrate urinary levels, total antioxidant capacity and selenium serum concentrations in 14 patients with chronic hepatitis C and in 9 healthy subjects. Before therapy, mean urinary nitrite/nitrate levels of patients were not different from those of healthy subjects, but after a 6-month treatment with alpha-interferon and ribavirin, these NO metabolites were higher in virologically negative patients (responders). Moreover, while no changes in selenium were observed in all patients, total antioxidant capacity was significantly higher in non-responders and well correlated with hyperuricemia (due to cell damage) observed in these subjects. Instead, uric acid decreased as free molecule in serum in responders, while we found the excretion of high NO levels as nitrite/nitrate. Our data allow us to hypothesize a role for NO as predictive of the success of therapy, since nitrite/nitrate increase in the urine of some patients precedes disappearance of the virus observed at the end of therapy.