Oxidative stress in chronic hepatitis C: the effect of interferon therapy and correlation with pathological features.
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.
Serejo
Fátima
F
Centre of Gastroenterology, Institute of Molecular Medicine, University of Lisbon, Lisbon, Portugal. fatima_serejo@netcabo.pt
Emerit
Ingrid
I
Filipe
Paulo Manuel
PM
Fernandes
Afonso Camilo
AC
Costa
Maria Adília
MA
Freitas
João Pedro
JP
de Moura
Miguel Carneiro
MC
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
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