Oxidative stress in chronic hepatitis C: The effect of interferon therapy and correlation with pathological features

AIMS: To evaluate the oxidative stress parameters before, during and after interferon treatment. PATIENTS / METHODS: Twenty patients were treated with interferon alpha2b 5 MU, three times a week, subcutaneously, for 12 months. Liver biopsy was performed six months before treatment and at the six month follow-up. Chromosomal breakage studies were evaluated by the adjusted clastogenic score (ACS, normal value [nv] 1.1+/-2.4%). Plasma malondialdehyde (MDA) was measured according to the Yagi method (nv 6.6+/-1.4 nmol/mL) and total thiols using the Ellman's reagent (DTNB) (nv 9.8+/-1.3 mumol/g protein). A serum marker of fibrogenesis, the amino-terminal propeptide of Procollagen type III (PIMP), was quantified by radioimmunoassay (nv 0.37+/-0.18 U/L). RESULTS: Compared with reference samples, the plasma of patients before treatment showed an increase of ACS (9.2+/-3.2%, P<0.001); higher MDA values (12.6+/-2.7 nmol/mL, P<0.001) and total plasma sulfhydryl groups (t-SH) were decreased (6.3+/-1.1 mumol/g protein, P<0.001). During treatment and at the follow-up, a decrease in ACS was noticed in all patients (P<0.001), but without normalization; a decrease in MDA was seen, with progressive normalization until the end of the follow up only in sustained responders (P<0.003), while an increase of t-SH was seen, with progressive normalization until the end of follow up in all patients (P<0.005). A positive correlation of ACS with grading of inflammation was found (r=0.52, P<0.03) but not with fibrosis staging. In contrast, plasma MDA correlates with fibrosis staging (r=0.51, P<0.03) and with PHIP (r=0.57, P<0.03) but without grading of inflammation. CONCLUSIONS: The present study confirmed the presence of oxidative stress in chronic hepatitis C patients. Interferon promotes a long term inhibition of oxidative stress with concomitant improvement of activity and fibrosis. In the management of chronic hepatitis C, adjuvant therapy with antioxidants could be useful.