Affiliation:
1. Centre of Gastroenterology (Institute of Molecular Medicine), University of Lisbon, Lisbon, Portugal
2. Institut Biomédical des Cordeliers, University Paris VI, Paris, France
3. Centre of Metabolism and Endocrinology, University of Lisbon, Lisbon, Portugal
4. Department of Pathology, Santa Maria Hospital, University of Lisbon, Lisbon, Portugal
Abstract
AIMS: To evaluate the oxidative stress parameters before, during and after interferon treatment.PATIENTS/METHODS: Twenty patients were treated with interferon α2b 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 µmol/g protein). A serum marker of fibrogenesis, the amino-terminal propeptide of Procollagen type III (PIIIP), 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±2.7nmol/mL, P<0.001) and total plasma sulfhydryl groups (t-SH) were decreased (6.3±1.1 µmol/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 PIIIP (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.
Subject
Gastroenterology,General Medicine
Cited by
39 articles.
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