title: Impact of interferon-alpha treatment on liver fibrosis in patients with chronic hepatitis B: an overview of published trials.
abstract: BACKGROUND
  The impact of interferon treatment in patients with hepatitis B virus (HBV) infection on fibrosis progression in comparison with its natural history has yet to be assessed in any large-scale randomized studies. The present report is a review of the evidence-based data published so far.
  
  
  METHODS
  Studies were included if they had at least two repeated estimates of liver fibrosis per patient treated with interferon-alpha (whether pegylated or not). Meta-analysis was performed using a random-effects model.
  
  
  RESULTS
  Altogether, 13 studies were included in the review, involving a total of 707 HBV patients treated with interferon-alpha-2a or -2b for 12-83 months. Only one study included pegylated interferon as monotherapy. A total of 787 untreated patients were also followed. Only one study used a non-invasive biomarker. There was a significant reduction in the fibrosis progression rate, with a risk reduction of 0.49 (95% CI: -0.64--0.34; chi(2)=119; degrees of freedom [DF]=6; P<0.0001), and significant heterogeneity (Cochran Q=81; P<0.0001). This significant impact was similar for both randomized (reduction of risk: -0.45; 95% CI: -0.64--0.26; P<0.0001) and not-randomized (controlled) studies (reduction of risk: -0.53; 95% CI: -0.79--0.28; P<0.0001).
  
  
  CONCLUSIONS
  According to these findings, the benefit of interferon treatment on fibrosis progression is clinically significant in patients with advanced fibrosis by the reduction of fibrosis progression to cirrhosis. Pegylated interferon now needs to be compared, in terms of benefit-risk factors, with the new generation of HBV treatments (such as entecavir and tenofovir), using non-invasive biomarkers.
authors.affiliation: Service d'hépatologie, UPMC Liver Center, hôpital La Pitié Salpêtrière, AP-HP, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France. tpoynard@teaser.fr
authors.forename: T
authors.initials: T
authors.lastname: Poynard
authors.forename: J
authors.initials: J
authors.lastname: Massard
authors.forename: M
authors.initials: M
authors.lastname: Rudler
authors.forename: A
authors.initials: A
authors.lastname: Varaud
authors.forename: P
authors.initials: P
authors.lastname: Lebray
authors.forename: J
authors.initials: J
authors.lastname: Moussalli
authors.forename: M
authors.initials: M
authors.lastname: Munteanu
authors.forename: Y
authors.initials: Y
authors.lastname: Ngo
authors.forename: D
authors.initials: D
authors.lastname: Thabut
authors.forename: Y
authors.initials: Y
authors.lastname: Benhamou
authors.forename: V
authors.initials: V
authors.lastname: Ratziu
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018450:Disease Progression; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha