title: Changes in histological lesions and serum fibrogenesis markers in chronic hepatitis C patients non-responders to interferon alpha.
abstract: OBJECTIVE
  The aim of this study was to evaluate the changes in histological lesions and serum N-terminal peptide of type III procollagen (PIIINP) and hyaluronate (HA) levels in virologic non-responder patients treated by Interferon alpha (IFNalpha).
  
  
  METHODS
  We enrolled 183 patients treated by IFNalpha and 56 controls, all with paired biopsy specimens. Yearly liver fibrosis progression was estimated before and during a follow-up of 1 year.
  
  
  RESULTS
  By contrast to sustained responders, non-responders (n = 105) did not achieve improvement of histological scores after therapy. Their yearly fibrosis progression rate was similar before and during follow-up (0.18, 95%CI: 0.16-0.20, vs 0.26 (95%CI: 0.12-0.40) fibrosis units/year, NS), and was not different in controls (0.17, 95%CI: 0.06-0.27). The levels of PIIINP and hyaluronate (HA) remained unchanged during follow-up. Histological improvement was observed for the second biopsy in 25% of non-responders, but also in 23% of controls. This improvement was not correlated with decrease of ALT level, viral load, PIIINP, or HA.
  
  
  CONCLUSIONS
  Our results suggest that IFNalpha therapy is unable to decrease PIIINP or HA levels and cannot improve the histological outcome in virologic non-responder patients. The histological improvement observed in a subset of patients may be linked to sample fluctuation or lack of reproducibility of histological scores.
authors.affiliation: Department of Gastroenterology and Hepatology, C.H.U. Grenoble, France.
authors.forename: V
authors.initials: V
authors.lastname: Leroy
authors.forename: C
authors.initials: C
authors.lastname: De Traversay
authors.forename: R
authors.initials: R
authors.lastname: Barnoud
authors.forename: J D
authors.initials: JD
authors.lastname: Hartmann
authors.forename: M
authors.initials: M
authors.lastname: Baud
authors.forename: D
authors.initials: D
authors.lastname: Ouzan
authors.forename: J P
authors.initials: JP
authors.lastname: Zarski
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D017211:Treatment Failure
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D016898:Interferon-alpha; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D006820:Hyaluronic Acid