OBJECTIVES: The mechanism explaining the strong association between IL28B rs12979860 polymorphisms and treatment outcome in chronic hepatitis C remains unclear. We explore whether IL28B protein [interferon (IFN)-λ3] plasma levels may vary according to IL28B genotype and/or following pegylated IFN-α/ribavirin therapy. PATIENTS AND METHODS: A total of 112 HIV/hepatitis C virus (HCV)-coinfected patients who completed a course of pegylated IFN-α/ribavirin therapy were examined. Sustained virological response (SVR) was achieved by 56% of patients. IL28B rs12979860 alleles were genotyped using the 5' nuclease assay with specific TaqMan probes. A specific enzyme immunoassay was used to measure IFN-λ3 plasma levels before initiating anti-HCV therapy and at week 4 of treatment. RESULTS: No significant differences between CC and non-CC IL28B carriers were found at baseline, either in the proportion of patients with detectable IFN-λ3 plasma levels or in their median values. In contrast, median IFN-λ3 plasma levels at week 4 of therapy significantly increased with respect to baseline in CC carriers [34.3 (16.7-56.3) versus 15.6 (15.6-30.3) pg/mL, respectively; P < 0.0001], but not in CT/TT carriers. Unexpectedly, increases in IFN-λ3 at week 4 of therapy did not predict SVR. CONCLUSIONS: The exogenous administration of IFN-α may induce IFN-λ3 release in IL28B CC carriers, but not in CT/TT carriers. However, this finding does not account for the link between IL28B polymorphisms and treatment outcome.
OBJECTIVES: The mechanism explaining the strong association between IL28Brs12979860 polymorphisms and treatment outcome in chronic hepatitis C remains unclear. We explore whether IL28B protein [interferon (IFN)-λ3] plasma levels may vary according to IL28B genotype and/or following pegylated IFN-α/ribavirin therapy. PATIENTS AND METHODS: A total of 112 HIV/hepatitis C virus (HCV)-coinfectedpatients who completed a course of pegylated IFN-α/ribavirin therapy were examined. Sustained virological response (SVR) was achieved by 56% of patients. IL28Brs12979860 alleles were genotyped using the 5' nuclease assay with specific TaqMan probes. A specific enzyme immunoassay was used to measure IFN-λ3 plasma levels before initiating anti-HCV therapy and at week 4 of treatment. RESULTS: No significant differences between CC and non-CC IL28B carriers were found at baseline, either in the proportion of patients with detectable IFN-λ3 plasma levels or in their median values. In contrast, median IFN-λ3 plasma levels at week 4 of therapy significantly increased with respect to baseline in CC carriers [34.3 (16.7-56.3) versus 15.6 (15.6-30.3) pg/mL, respectively; P < 0.0001], but not in CT/TT carriers. Unexpectedly, increases in IFN-λ3 at week 4 of therapy did not predict SVR. CONCLUSIONS: The exogenous administration of IFN-α may induce IFN-λ3 release in IL28B CC carriers, but not in CT/TT carriers. However, this finding does not account for the link between IL28B polymorphisms and treatment outcome.
Authors: Paul Sheppard; Wayne Kindsvogel; Wenfeng Xu; Katherine Henderson; Stacy Schlutsmeyer; Theodore E Whitmore; Rolf Kuestner; Ursula Garrigues; Carl Birks; Jenny Roraback; Craig Ostrander; Dennis Dong; Jinu Shin; Scott Presnell; Brian Fox; Betty Haldeman; Emily Cooper; David Taft; Teresa Gilbert; Francis J Grant; Monica Tackett; William Krivan; Gary McKnight; Chris Clegg; Don Foster; Kevin M Klucher Journal: Nat Immunol Date: 2002-12-02 Impact factor: 25.606
Authors: Sergei V Kotenko; Grant Gallagher; Vitaliy V Baurin; Anita Lewis-Antes; Meiling Shen; Nital K Shah; Jerome A Langer; Faruk Sheikh; Harold Dickensheets; Raymond P Donnelly Journal: Nat Immunol Date: 2002-12-16 Impact factor: 25.606
Authors: Norma I Rallón; Susanna Naggie; José M Benito; José Medrano; Clara Restrepo; David Goldstein; Kevin V Shianna; Eugenia Vispo; Alex Thompson; John McHutchison; Vincent Soriano Journal: AIDS Date: 2010-05-15 Impact factor: 4.177
Authors: Tobias Marcello; Arash Grakoui; Giovanna Barba-Spaeth; Erica S Machlin; Sergei V Kotenko; Margaret R MacDonald; Charles M Rice Journal: Gastroenterology Date: 2006-10-01 Impact factor: 22.682
Authors: Nina Ank; Hans West; Christina Bartholdy; Kristina Eriksson; Allan R Thomsen; Søren R Paludan Journal: J Virol Date: 2006-05 Impact factor: 5.103
Authors: Dongliang Ge; Jacques Fellay; Alexander J Thompson; Jason S Simon; Kevin V Shianna; Thomas J Urban; Erin L Heinzen; Ping Qiu; Arthur H Bertelsen; Andrew J Muir; Mark Sulkowski; John G McHutchison; David B Goldstein Journal: Nature Date: 2009-08-16 Impact factor: 49.962
Authors: Mohammed Eslam; Duncan McLeod; Kebitsaone Simon Kelaeng; Alessandra Mangia; Thomas Berg; Khaled Thabet; William L Irving; Gregory J Dore; David Sheridan; Henning Grønbæk; Maria Lorena Abate; Rune Hartmann; Elisabetta Bugianesi; Ulrich Spengler; Angela Rojas; David R Booth; Martin Weltman; Lindsay Mollison; Wendy Cheng; Stephen Riordan; Hema Mahajan; Janett Fischer; Jacob Nattermann; Mark W Douglas; Christopher Liddle; Elizabeth Powell; Manuel Romero-Gomez; Jacob George Journal: Nat Genet Date: 2017-04-10 Impact factor: 38.330
Authors: Adrian Egli; Jyotshna Mandal; Desiree M Schumann; Michael Roth; Brad Thomas; D Lorne Tyrrell; Francesco Blasi; Kostantinos Kostikas; Wim Boersma; Branislava Milenkovic; Alicia Lacoma; Katharina Rentsch; Gernot G U Rohde; Renaud Louis; Joachim G Aerts; Tobias Welte; Antoni Torres; Michael Tamm; Daiana Stolz Journal: BMC Pulm Med Date: 2018-03-21 Impact factor: 3.317
Authors: Yi-Fan Lu; David M Mauger; David B Goldstein; Thomas J Urban; Kevin M Weeks; Shelton S Bradrick Journal: Sci Rep Date: 2015-11-04 Impact factor: 4.379
Authors: Scott A Read; Kate S O'Connor; Vijay Suppiah; Chantelle L E Ahlenstiel; Stephanie Obeid; Kristina M Cook; Anthony Cunningham; Mark W Douglas; Philip J Hogg; David Booth; Jacob George; Golo Ahlenstiel Journal: Nat Commun Date: 2017-05-17 Impact factor: 14.919