title: Meta-analysis: ribavirin plus interferon vs. interferon monotherapy for chronic hepatitic C - an updated Cochrane review.
abstract: BACKGROUND
  Multiple randomized trials have been published on antiviral treatment for chronic hepatitis C.
  
  
  OBJECTIVE
  To meta-analyse the effect of adding ribavirin to interferon for chronic hepatitis C.
  
  
  METHODS
  The results of randomized trials were combined in cumulative meta-analyses. Trial sequential analyses were used to adjust for spurious results because of random errors and multiplicity. The outcome measures were undetectable hepatitis C virus RNA in serum (sustained virological response) and liver-related morbidity plus all-cause mortality.
  
  
  RESULTS
  We included 82 randomized trials with 12 615 patients. Trial sequential analysis established clear beneficial effect of interferon plus ribavirin vs. interferon on the sustained virological response in 1998 after nine trials (RR: 0.74; 95% CI: 0.64-0.85, P < 0.0001, 1734 patients). Subsequently, additional 73 trials were published just narrowing the confidence interval and decreasing the P-value. By contrast, trial sequential analysis found that additional evidence is needed to convincingly detect a beneficial effect of interferon plus ribavirin vs. interferon monotherapy on clinical outcomes.
  
  
  CONCLUSIONS
  The rationale behind several recent trials on adding ribavirin to interferon for chronic hepatitis C is debatable as the effect on virological response is established. More evidence is needed to assess if adding ribavirin to interferon improves clinical outcomes.
authors.affiliation: Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Denmark. jesperb5@hotmail.com
authors.forename: J
authors.initials: J
authors.lastname: Brok
authors.forename: L-L
authors.initials: LL
authors.lastname: Gluud
authors.forename: C
authors.initials: C
authors.lastname: Gluud
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012254:Ribavirin / Q000627:therapeutic use*; D013223:Statistics as Topic; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D007372:Interferons