title: Response-guided peg-interferon plus ribavirin treatment duration in chronic hepatitis C: meta-analyses of randomized, controlled trials and implications for the future.
abstract: Response-guided pegylated interferon (peg-IFN) plus ribavirin (P/R) therapy trials on genotype (G)1 and G2/G3 hepatitis C virus-infected patients provide contradictory results. We conducted meta-analyses of randomized, controlled trials to address (1) the benefit of a 72-week extended-duration therapy in G1-slow responders and (2) adequate shortened duration therapy in G1 and G2/G3-rapid responders. Seventeen trials were selected, including 624 G1 rapid responders, 570 G1 slow responders, and 2,062 G2/G3 rapid responders. Virologic outcomes and treatment discontinuation data were collected from published articles and by asking investigators. Pooled estimates of sustained virologic response (SVR), relapse, and dropouts were calculated using the random effects model, considering the variability of shortened duration, ribavirin dose, genotype, and baseline viral load. In G1 slow responders, a 72-week extended duration increased SVR (+10.7%; 95% CI [confidence interval]: +4.4% to + 17.1%), decreased relapse (-12.3%; 95% CI: -25.4% to 0%), and did not significantly increase drop-out rates (+4.5%; 95% CI: -0.6% to + 9.6%). The benefit of extended duration was lower when using a weight-based ribavirin regimen (+8.7%; 95% CI: +1.7% to + 15.8%). In G1 rapid responders, a 24-week shortened duration decreased SVR (-12.5%; 95% CI: -19.2% to -5.8%) and increased relapse rates (+8.8%; 95% CI: +2.9% to + 14.8%). Such differences were not significant in patients with baseline viral load <400,000 UL/mL (-4.4%; 95% CI: -9.8% to + 1%). In G2/G3 rapid responders, SVR was more common for standard 24-week duration than for shortened durations (+4.1%; 95% CI: +0.1% to + 8.5), but this benefit was not significant when ribavirin was weight-adjusted and the short duration was 16 weeks (-1.7%; 95% CI: -6.1% to + 2.7%) and for G2 patients (+1.6%; 95% CI: -0.2% to + 5.5%).
  
  
  CONCLUSIONS
  Long durations of P/R therapy improve SVR, regardless of genotype. This effect is nonetheless negligible in rapid responders, with the most favorable conditions for SVR (G2, G1 with low viral load, and G3 with weight-adjusted ribavirin regimen).
authors.affiliation: Service d'Hépatologie, CHU Jean Minjoz, Besançon, France. vdimartino@chu-besancon.fr
authors.forename: Vincent
authors.initials: V
authors.lastname: Di Martino
authors.forename: Carine
authors.initials: C
authors.lastname: Richou
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Cervoni
authors.forename: Jose M
authors.initials: JM
authors.lastname: Sanchez-Tapias
authors.forename: Donald M
authors.initials: DM
authors.lastname: Jensen
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.forename: Frances
authors.initials: F
authors.lastname: Sheppard
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.forename: Thierry
authors.initials: T
authors.lastname: Thévenot
mesh_terms: D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage*; D019562:Viral Load
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a