title: Oxidative stress in chronic hepatitis C: the effect of interferon therapy and correlation with pathological features.
abstract: OBJECTIVE
  To evaluate the oxidative stress parameters before, during and after interferon treatment.
  
  
  METHODS
  Twenty patients were treated with interferon a2b 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 micromol/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 +/- 2.7 nmol/mL, P<0.001) and total plasma sulfhydryl groups (t-SH) were decreased (6.3 +/- 1.1 micromol/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.
authors: Centre of Gastroenterology, Institute of Molecular Medicine, University of Lisbon, Lisbon, Portugal. fatima_serejo@netcabo.pt
authors: Fátima
authors: F
authors: Serejo
authors: Ingrid
authors: I
authors: Emerit
authors: Paulo Manuel
authors: PM
authors: Filipe
authors: Afonso Camilo
authors: AC
authors: Fernandes
authors: Maria Adília
authors: MA
authors: Costa
authors: João Pedro
authors: JP
authors: Freitas
authors: Miguel Carneiro
authors: MC
authors: de Moura
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D001707:Biopsy, Needle; D019457:Chromosome Breakage; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011994:Recombinant Proteins
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010446:Peptide Fragments; D011347:Procollagen; D011994:Recombinant Proteins; C041876:procollagen Type III-N-terminal peptide; D008315:Malondialdehyde; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase