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

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

Response-guided Peg-interferon plus ribavirin treatment duration in chronic

hepatitis C: Meta-analyses of randomized controlled trials and implications for

the future.

Di o V, Richou C, Cervoni JP, -Tapias JM, Jensen DM, Mangia A, Buti

M, Sheppard F, Ferenci P, Thévenot T.

Source

Service d'hépatologie, CHU Minjoz, Besançon, France; EA API 4266,

Université de Franche Comté. vdimartino@....

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.

PMID: 21674553 [PubMed - as supplied by publisher]