Interleukin 28B polymorphism predicts pegylated interferon plus ribavirin treatment outcome in chronic hepatitis C genotype 4

被引:72
作者
De Nicola, Stella [1 ]
Aghemo, Alessio [1 ]
Rumi, Maria Grazia [2 ]
Galmozzi, Enrico [1 ]
Valenti, Luca [3 ]
Soffredini, Roberta [1 ]
De Francesco, Raffaele [4 ]
Prati, Gian Maria [1 ]
D'Ambrosio, Roberta [1 ]
Cheroni, Cristina [4 ]
Donato, Maria Francesca [1 ]
Colombo, Massimo [1 ]
机构
[1] Univ Milan, Div Gastroenterol 1, Fdn IRCCS,Ctr AM & A Migliavacca, Ca Granda Osped Maggiore Policlin, I-20122 Milan, Italy
[2] Univ Milan, Div Hepatol, Osped San Giuseppe IRCCS Multimed, I-20122 Milan, Italy
[3] Univ Milan, Dept Internal Med, Fdn IRCCS, Ca Granda Osped Maggiore Policlin, I-20122 Milan, Italy
[4] Ist Nazl Genet Mol Milano, INGM, Milan, Italy
关键词
SUSTAINED VIROLOGICAL RESPONSE; GENETIC-VARIATION; PEGINTERFERON ALPHA-2A; IL28B GENOTYPE; INFECTION;
D O I
10.1002/hep.24683
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) region are the strongest baseline predictors of a sustained virologic response (SVR) to peg-interferon (PegIFN) and ribavirin (Rbv) in patients with hepatitis C virus (HCV) genotype 1 infection. Whether this holds true for HCV-4 patients too is unknown. The aim was to investigate the predictive power of the rs12979860 IL28B SNP for a response to Peg-IFN and Rbv in HCV-4 patients. All HCV-4 patients consecutively treated between September 2004 and June 2010 with PegIFN and Rbv at two liver centers at the Maggiore Hospital Milan (Italy) underwent TaqMan SNP Genotyping assays for testing rs12979860 genotype. Of 112 treated patients (98 males, 75 of Egyptian descent, 26 with cirrhosis) 103 were included in the final analysis; five discontinued treatment for nonvirologic reasons and four did not consent to genetic testing. Twenty-four (23%) were genotype CC, 65 (63%) CT, and 14 (14%) TT. Overall, 50 (49%) achieved an SVR: 21 (88%) CC patients versus 29 (37%) CT/TT (P < 0.0001). CC patients more often had a rapid virologic response (RVR) than CT/TT patients (12, 50% versus 23, 29%; P = 0.08), while also showing lower relapse rates (0% [0/21] versus 36% [16/45] P = 0.0013). In non-RVR patients, SVR rates were higher in CC than CT/TT patients (9 [75%] versus 13 [23%] P = 0.001). By logistic regression, the IL28B rs12979860 CC genotype was an independent predictor of SVR with an odds ratio of 8.0 (95% confidence interval 2.00-32.01; P = 0.003). Conclusion: The IL28B rs12979860 SNP may have an added value in the treatment algorithm of HCV-4 patients because it is the strongest predictor of an SVR to PegIFN/Rbv therapy. (HEPATOLOGY 2012)
引用
收藏
页码:336 / 342
页数:7
相关论文
共 32 条
[1]   Hepatitis C Pharmacogenetics: State of the Art in 2010 [J].
Afdhal, Nezam H. ;
McHutchison, John G. ;
Zeuzem, Stefan ;
Mangia, Alessandra ;
Pawlotsky, Jean-Michel ;
Murray, Jeffrey S. ;
Shianna, Kevin V. ;
Tanaka, Yasuhito ;
Thomas, David L. ;
Booth, David R. ;
Goldstein, David B. .
HEPATOLOGY, 2011, 53 (01) :336-345
[2]   RESULTS OF A PROOF OF CONCEPT STUDY (C210) OF TELAPREVIR MONOTHERAPY AND IN COMBINATION WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN IN TREATMENT-NAIVE GENOTYPE 4 HCV PATIENTS [J].
Benhamou, Y. ;
Moussalli, J. ;
Ratziu, V. ;
Lebray, P. ;
Gysen, V. ;
de Backer, K. ;
Ghys, A. ;
van Heeswijk, R. ;
Vangeneugden, I. ;
Picchio, G. ;
Beumont-Mauviel, M. .
JOURNAL OF HEPATOLOGY, 2009, 50 :S6-S6
[3]   Epidemiological profile of 806 Italian children with hepatitis C virus infection over a 15-year period [J].
Bortolotti, Flavia ;
Jorio, Raffaele ;
Resti, Massimo ;
Camma, Calogero ;
Marcellini, Matilde ;
Giacchino, Raffaella ;
Marazzi, Maria Grazia ;
Verucchi, Gabriella ;
Zancan, Lucia ;
Barbera, Cristiana ;
Maggiore, Giuseppe ;
Vajro, Pietro ;
Giannattasio, Antonietta ;
Bartolacci, Samuela .
JOURNAL OF HEPATOLOGY, 2007, 46 (05) :783-790
[4]   IL28B Genomic-Based Treatment Paradigms for Patients With Chronic Hepatitis C Infection: The Future of Personalized HCV Therapies [J].
Clark, Paul J. ;
Thompson, Alex J. ;
McHutchison, John G. .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2011, 106 (01) :38-45
[5]  
Craxì A, 2011, J HEPATOL, V55, P245, DOI 10.1016/j.jhep.2011.02.023
[6]   HCV genotype 4 in Belgium: three distinct patterns among patients from European and African origin [J].
Delwaide, Jean ;
Reenaers, Catherine ;
Gerard, Christiane ;
Vaira, Dolores ;
Bastens, Boris ;
Servais, Benoit ;
Bekhti, Abdelaziz ;
Bataille, Christian ;
Wain, Etienne ;
De Leeuw, Pascal ;
Daenen, Guy ;
Mesureur, Thierry ;
Sente, Jean-Marie ;
Belaiche, Jacques .
EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY, 2006, 18 (07) :707-712
[7]   A tetra-primer amplification refractory mutation system polymerase chain reaction for the evaluation of rs12979860 IL28B genotype [J].
Galmozzi, E. ;
Del Menico, B. ;
Rametta, R. ;
Dongiovanni, P. ;
Fracanzani, A. L. ;
Benedan, L. ;
Borroni, V. ;
Maggioni, P. ;
Fargion, S. ;
Valenti, L. .
JOURNAL OF VIRAL HEPATITIS, 2011, 18 (09) :628-630
[8]   Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance [J].
Ge, Dongliang ;
Fellay, Jacques ;
Thompson, Alexander J. ;
Simon, Jason S. ;
Shianna, Kevin V. ;
Urban, Thomas J. ;
Heinzen, Erin L. ;
Qiu, Ping ;
Bertelsen, Arthur H. ;
Muir, Andrew J. ;
Sulkowski, Mark ;
McHutchison, John G. ;
Goldstein, David B. .
NATURE, 2009, 461 (7262) :399-401
[9]   Diagnosis, Management, and Treatment of Hepatitis C: An Update [J].
Ghany, Marc G. ;
Strader, Doris B. ;
Thomas, David L. ;
Seeff, Leonard B. .
HEPATOLOGY, 2009, 49 (04) :1335-1374
[10]  
Gryseels B, 2006, LANCET, V368, P1106, DOI [10.1016/S0140-6736(06)69440-3, 10.1016/S0140-6736(13)61949-2]