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Gastroenterology. 2012 Sep;143(3):608-18.e1-5. doi: 10.1053/j.gastro.2012.05.011. Epub 2012 May 21.

Factors that predict response of patients with hepatitis C virus infection to boceprevir.

Collaborators (268)

Delwaide J, Horsmans Y, Van Vlierberghe H, Anderson F, Feinman SV, Heathcote J, Marotta P, Ramji A, Wong F, Peltakian K, Kaita K, Alric L, Ben Ali S, Bigard MA, Bourliere M, Boyer-Darrigrand N, Bronowicki JP, De Ledinghen V, Hezode C, Lebray P, Marcellin P, Maynard-Muet M, Pol S, Poynard T, Tran A, Trepo C, Truchi R, Vallet-Pichard A, Berg T, Guenther R, Lohse AW, Manns M, Niederau C, Schmidt W, Spengler U, Wedemeyer H, Zeuzem S, Carosi G, Colombo M, Craxì A, Rizzetto M, Zignego A, Zuin M, Reymunde A, Buti Ferret M, Esteban R, Afdhal N, Bacon B, Balart L, Bennett M, Box T, Boyer T, Davis M, Flamm S, Freilich B, Galati J, Galler G, Gibas A, Godofsky E, Gordon S, Herrera J, Herrine S, Jacobson I, King J, Kwo P, Lawitz E, Lee W, Levin J, Luketic V, McCone J, McHutchison J, Mullen K, Morgan T, Muir A, Nunes F, Nyberg A, Nyberg L, Pauly MP, Peine C, Poordad F, Ravendhran N, Reindollar R, Riley T, Rossaro L, Rubin R, Ryan M, Schiff E, Sherman K, Shiffman M, Strauss R, Vierling J, Yapp R, Goodman Z, Colombato L, Curciarello J, Silva M, Tanno H, Terg R, Adler M, Langlet P, Lasser L, Nevens F, Anderson F, Bailey R, Bilodeau M, Cooper C, Feinman S, Heathcote J, Levstik M, Ramji A, Sherman M, Shafran S, Yoshida E, Achim A, Ben Ali S, Bigard MA, Bonny C, Bourliere M, Boyer-Darrigrand N, Bronowicki JP, Canva V, Couzigou P, De Ledinghen V, Guyader D, Hezode C, Larrey D, Latournerie M, Marcellin P, Mathurin P, Maynard-Muet M, Moussalli J, Poupon R, Poynard T, Serfaty L, Tran A, Trepo C, Truchi R, Zarski JP, Berg T, Dikopoulos N, Eisenbach C, Galle P, Gerken G, Goeser T, Gregor M, Klass D, Kraus M, Niederau C, Schlaak J, Schmid R, Thies P, Schmidt K, Thimme R, Weidenbach H, Zeuzem S, Angelico M, Bruno S, Carosi G, Craxì A, Mangia A, Pirisi M, Rizzetto M, Taliani G, Zignego A, Reesink HW, Serejo F, Reymunde A, Rosado B, Torres E, Barcena Marugan R, De La Mata M, Calleja JL, Castellano G, Diago M, Esteban R, Fernandez C, Sanchez Tapias J, Serra Desfilis M, Afdhal N, Al-Osaimi A, Bacon B, Balart L, Bennett M, Bernstein D, Black M, Bowlus C, Boyer T, Dalke D, Davis C, Davis G, Davis M, Everson G, Felizarta F, Flamm S, Freilich B, Galati J, Galler G, Ghalib R, Gibas A, Godofsky E, Gordon F, Gordon S, Gross J, Harrison S, Herrera J, Herrine S, Hu KQ, Imperial J, Jacobson I, Jones D, Kilby A, King J, Koch A, Kowdley K, Krawitt E, Kwo P, Lambiase L, Lawitz E, Lee W, Levin J, Levine R, Li X, Lok A, Luketic V, Mailliard M, McCone J, McHutchison J, Mikolich D, Morgan T, Muir A, Nelson D, Nunes F, Nyberg A, Nyberg L, Pandya P, Pauly M, Peine C, Poleynard G, Poordad F, Pound D, Poulos J, Rabinovitz M, Ravendhran N, Ready J, Reddy K, Reindollar R, Reuben A, Riley T, Rossaro L, Rubin R, Ryan M, Santoro J, Schiff E, Sepe T, Sherman K, Shiffman M, Sjogren M, Sjogren R, Smith C, Stein L, Strauss R, Sulkowski M, Szyjkowski R, Vargas H, Vierling J, Witt D, Yapp R, Younes Z.

Abstract

BACKGROUND & AIMS:

Little is known about factors associated with a sustained virologic response (SVR) among patients with hepatitis C virus (HCV) infection to treatment with protease inhibitors.

METHODS:

Previously untreated patients (from the Serine Protease Inhibitor Therapy 2 [SPRINT-2] trial) and those who did not respond to prior therapy (from the Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 [RESPOND-2] trial) received either a combination of peginterferon and ribavirin for 48 weeks or boceprevir, peginterferon, and ribavirin (triple therapy) after 4 weeks of peginterferon and ribavirin (total treatment duration, 28-48 wk). A good response to interferon was defined as a ≥ 1 log(10) decrease in HCV RNA at week 4; a poor response was defined as a <1 log(10) decrease. We used multivariate regression analyses to identify baseline factors of the host (including the polymorphism interleukin [IL]-28B rs12979860) associated with response. The polymorphism IL-28B rs8099917 also was assessed.

RESULTS:

In the SPRINT-2 trial, factors that predicted a SVR to triple therapy included low viral load (odds ratio [OR], 11.6), IL-28B genotype (rs 12979860 CC vs TT and CT; ORs, 2.6 and 2.1, respectively), absence of cirrhosis (OR, 4.3), HCV subtype 1b (OR, 2.0), and non-black race (OR, 2.0). In the RESPOND-2 trial, the only factor significantly associated with a SVR was previous relapse, compared with previous nonresponse (OR, 2.6). Most patients with rs12979860 CC who received triple therapy had undetectable levels of HCV RNA by week 8 (76%-89%), and were eligible for shortened therapy. In both studies, IL-28B rs12979860 CC was associated more strongly with a good response to interferon than other baseline factors; however, a ≥ 1 log(10) decrease in HCV-RNA level at week 4 was associated more strongly with SVR than IL-28B rs12979860. Combining the rs8099917 and rs12979860 genotypes does not increase the association with SVR.

CONCLUSIONS:

The CC polymorphism at IL-28B rs12979860 is associated with response to triple therapy and can identify candidates for shorter treatment durations. A ≥ 1 log(10) decrease in HCV RNA at week 4 of therapy is the strongest predictor of a SVR, regardless of polymorphisms in IL-28B.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00705432 NCT00708500.

Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID:
22626609
[PubMed - indexed for MEDLINE]
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