Interleukin 28B polymorphism impact on early HCV kinetics in HCV-infected liver transplant recipients undergoing antiviral therapy
Abstract
Aim. To estimate the impact of recipient IL28B genotypes on rapid (RVR) and early virologic responses (EVR) pattern in liver transplant recipients undergoing antiviral treatment (AVT).
Material and methods. Blood samples were screened for single nucleotide polymorphisms (SNP) near the IL28B genes (rs8099917 T ≥G and rs12979860 C>T) by kit «AmpliSens® Genoscreen-IL28B-FL» (CRIE) in 24 HCV-infected recipients. All the patients underwent pegylated interferon-alfa with (n=21) or without (n=3) ribavirin at least for 12 weeks.
Results. Five recipients achieved RVR (one has HCV genotype 1 and 4 patients – HCV genotype 2 or 3) and other 10 – complete EVR. In 6 cases slow virologic response (aviremia between 12 and 24 weeks of treatment, SlVR) occurred. Three patients remained non-responders. G-allele (rs80999917) was present in 3 (20%) out of 15 pts. with complete EVR and in 5 out of 6patients with SlVR (p=0.014). Genotype C/C (rs12979860) was present in 6 (40%) patients with complete EVR and in none of slow-responders (one-sided p=0.041).The groups of recipients with and without complete EVR were comparable with sex, age, pre-treatment viral load, immunosuppression (cyclosporine vs. tacrolimus), weight and body mass index, and mean ribavirin dose. The only pre-treatment factors which have impact on complete EVR were genotype (1 vs. non-1) and IL28B polymorphisms.
Conclusion. The SNP in IL28B region may predict slow response to AT in post-LTx setting and should be considered when AT duration is planning.
About the Authors
V. E. SyutkinRussian Federation
V. P. Chulanov
Russian Federation
I. V. Karandashova
Russian Federation
V. A. Dolgin
Russian Federation
A. O. Chugunov
Russian Federation
References
1. Сюткин В.Е. Новые возможности повышения эффективности противовирусной терапии больных хроническим гепатитом С // Инфекционные болезни. – 2009. – Т. 7, № 2. – P. 55–59.
2. Afdhal N.H., McHutchison J.G., Zeuzem S. et al. Hepatitis C pharmacogenetics: state of the art in 2010 // Hepatology. – 2011. – Vol. 53, N 1. – P. 336–345.
3. Charlton M.R., Thompson A., Veldt B.J. et al. Interleukin-28B polymorphisms are associated with histological recurrence and treatment response following liver transplantation in patients with hepatitis C virus infection // Hepatology. – 2011. – Vol. 53, N 1. – P. 317–324.
4. Coto-Llerena M., Perez-Del-Pulgar S., Crespo G. et al. Donor and recipient IL28B polymorphisms in HCVinfected patients undergoing antiviral therapy before and after liver transplantation // Am. J. Transplant. – 2011. – Vol. 11, N 5. – P. 1051–1057.
5. Dienstag J.L., McHutchison J.G. American Gastroenterological Association medical position statement on the management of hepatitis C // Gastroenterology. – 2006. – Vol. 130, N 1. – P. 225–230.
6. Eurich D., Boas-Knoop S., Ruehl M. et al. Relationship between the interleukin-28b gene polymorphism and the histological severity of hepatitis C virus-induced graft inflammation and the response to antiviral therapy after liver transplantation // Liver Transpl. – 2011. – Vol. 17, N 3. – P. 289–298.
7. Fukuhara T., Taketomi A., Motomura T. et al. Variants in IL28B in liver recipients and donors correlate with response to peg-interferon and ribavirin therapy for recurrent hepatitis C // Gastroenterology. – 2010. – Vol. 139, N 5. – P. 1577–1585.
8. Ge D., Fellay J., Thompson A.J. et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance // Nature. – 2009. – Vol. 461, N 7262. – P. 399–401.
9. Lange C.M., Moradpour D., Doehring A. et al. Impact of donor and recipient IL28B rs12979860 genotypes on hepatitis C virus liver graft reinfection // J. Hepatol. – 2011. – Vol. 55, N 2. – P. 322-327.
10. Mangia A., Thompson A.J., Santoro R. et al. An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response // Gastroenterology. – 2010. – Vol. 139, N 3. – P. 821–827.
11. Neumann A.U., Bibert S., Haagmans B.L. et al. DITTO-HCV Group. IL28B polymorphism is significantly correlated with IFN anti-viral effictiveness already on first day of pegylated interferon-A and ribavirin therapy of chronic HCV infection [Abstract 2011] // J. Hepatol. – 2010. – Vol. 52 (suppl. 1). – P. 468.
12. Rauch A., Kutalik Z., Descombes P. et al. Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study // Gastroenterology. – 2010. – Vol. 138, N 4. – P. 1338–1345.
13. Suppiah V., Moldovan M., Ahlenstiel G. et al. IL28B is associated with response to chronic hepatitis C interferonalpha and ribavirin therapy // Nat. Genet. – 2009. – Vol. 41, N 10. – P. 1100–1104.
14. Tanaka Y., Nishida N., Sugiyama M. et al. Genomewide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C // Nat. Genet. – 2009. – Vol. 41, N 10. – P. 1105–1109.
15. Thompson A.J., Muir A.J., Sulkowski M.S. et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus // Gastroenterology. – 2010. – Vol. 139, N 1. – P. 120–129.
16. Ueda Y., Takada Y., Marusawa H. et al. Clinical features of biochemical cholestasis in patients with recurrent hepatitis C after living-donor liver transplantation // J. Viral. Hepatol. – 2010. – Vol. 17, N 7. – P. 481–487.
Review
For citations:
Syutkin V.E., Chulanov V.P., Karandashova I.V., Dolgin V.A., Chugunov A.O. Interleukin 28B polymorphism impact on early HCV kinetics in HCV-infected liver transplant recipients undergoing antiviral therapy. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2011;21(6):49-55. (In Russ.)
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