Response-guided Peg-interferon plus ribavirin treatment duration in chronic hepatitis C: Meta-analyses of randomized controlled trials and implications for the future

Hepatology. 2011 Jun 14. doi: 10.1002/hep.24480. [Epub ahead of print]

Di Martino V, Richou C, Cervoni JP, Sanchez-Tapias JM, Jensen DM, Mangia A, Buti M, Sheppard F, Ferenci P, Thévenot T.

Service d'hépatologie, CHU Jean Minjoz, Besançon, France; EA API 4266, Université de Franche Comté. vdimartino@chu-besancon.fr.

Abstract

Response-guided peg-interferon plus ribavirin (P/R) therapy trials on genotype(G)1 and G2/G3 HCV-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 2062 G2/G3-rapid responders. Virologic outcomes and treatment discontinuation data were collected from published papers and by asking authors. 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:+4.4%-+17.1%), decreased relapse (-12.3%, 95%CI:-25.4%-0%), and did not significantly increase drop-out rates (+4.5%, 95%CI:-0.6%-+9.6%). The benefit of extended duration was lower when using weight-based ribavirin regimen (+8.7%, 95%CI:+1.7%-+15.8%). In G1-rapid responders, a 24 week-shortened duration decreased SVR (-12.5%, 95%CI:-19.2%--5.8%), and increased relapse rates (+8.8%, 95%CI:+2.9%- +14.8%). Such differences were not significant in patients with baseline viral load <400,000UI/mL (-4.4%, 95%CI:-9.8%-+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%-+8.5), but this benefit was not significant when the ribavirin was weight-adjusted and the short duration was 16 weeks (-1.7%, 95%CI:-6.1% -+2.7%), and for G2 patients (+1.6%, 95%CI: -0.2%-+5.5%). In Conclusion, long durations of P/R therapy improve SVR, regardless of genotype. This effect is nonetheless negligible in rapid responders with the most favourable conditions for SVR (G2, G1 with low viral load, and G3 with weight-adjusted ribavirin regimen). (HEPATOLOGY 2011.).

Copyright © 2011 American Association for the Study of Liver Diseases.

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