• Features of progression of chronic hepatitis C in children with different variants of polymorphism of the gene IL-28B 

Features of progression of chronic hepatitis C in children with different variants of polymorphism of the gene IL-28B 

SOVREMENNAYA PEDIATRIYA.2016.1(73):120-126; doi 10.15574/SP.2016.73.126 

Features of progression of chronic hepatitis C in children with different variants of polymorphism of the gene IL-28B 

Berezenko V. S., Tsaryova O. V., Dyba M. B.

SI «Institute of Pediatrics, Obstetrics and Gynecology of NAMS of Ukraine», Kyiv, Ukraine

Regional Hospital of Infectious Diseases, Zaporizhzhya, Ukraine 

Purpose. To study the features of the progression of chronic hepatitis C in children with different variants of polymorphism of the gene IL-28B. 

Materials and methods. The study involved 57 children aged 3–18 years with CHC. All patients were involved in clinical, laboratory and instrumental examination. The stage of fibrosis was assessed morphologicallyon a scale METAVIR, by the calculation method — Fibro Test, on APRI index, and by the concentration of hyaluronic acid (HA), transforming growth factor TGF- β1 in serum usingIFA. The SNP genotypes of rs8099917 and rs12979860 lociin IL-28B were determinedby the method of the polymer chain reaction (PCR). A statistical analysis of the data was conducted. 

Resume. Most of the patients were children with chronic hepatitis C who had genotype CT at rs12979860 locus of the gene IL-28B (54%) and the TT geno-type at rs8099917 locus (60%). It was found that fibrogenesis in the liver of patients with chronic hepatitis C depends on the polymorphism of the gene IL-28B. Unfavorable genotypevariants for the development of liver fibrosis are: TT (rs12979860), CT (rs12979860) and TG/GG (rs8099917). Variants CC (rs12979860) and TT (rs8099917) have a beneficial effect on the course of chronic hepatitis C, including patients with a lower stage of fibrosis. To determine the risk of progression of chronic hepatitis C it may be sufficient to determine the polymorphism of rs12979860locusin the gene IL-28B. 

Conclusions.The polymorphism variants CC (rs12979860) and TT (rs8099917)of the gene IL-28Bare more favorable (lower severity of fibrosis) in the progression of chronic hepatitis C in children. Variant TT (rs12979860) in the polymorphism of the gene IL-28B is associated with the progression of hepatitis — faster development of liver fibrosis. 

Key words: children, chronic hepatitis C, polymorphism of the gene IL-28B, fibrosis, hyaluronic acid, transforming growth factor β1
 

REFERENCES

1. Lopatkina TN, Kudlinskiy IS. 2011. Rol polimorfizma gena interleykina 28V v otsenke effektivnosti protivovirusnoy terapii hronicheskogo gepatita S. Klin gepatologiya. 2: 28—38.

2. Surkov AN. 2009. Syivorotochnyie markeryi fibrozirovaniya pri hronicheskih zabolevaniyah pecheni u detey. Avtoref dis k med n. 14.00.09. Nauchnyiy tsentr zdorovya detey RAMN. Moskva: 25.

3. Uchaykin VF, Nisevich NI, Cherednichenko TV. 2003. Virusnyie gepatityi ot A do TTV u detey. Moskva, Novaya volna: 432.

4. Yanchenko VI. 2014. Morfologicheskie izmeneniya v pecheni u bolnyih HGS v zavisimosti ot polimorfizma gena interleykina IL28V u bolnyih s hronicheskim gepatitom Sna Ukraine. Portal infektsionnyih bolezney. 16.07.2014.

5. Wai CT, Greenson JK, Fontana RJ et al. 2003. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis. Hepatology. 38(2): 518—526. http://dx.doi.org/10.1053/jhep.2003.50346; PMid:12883497

6. Mangia A, Thompson AJ, Santoro R et al. 2010. An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologist response. Gastroenterology. 139(3): 821—827.

7. Noureddin M, Wright EC, Alter HJ et al. 2013. Association of IL28B genotype with fibrosis progression and clinical out-comes in patients with chronic hepatitis C: A longitudinal analysis. Hepatology. 58(5): 1548—1557. http://dx.doi.org/10.1002/hep.26506; PMid:23703931 PMCid:PMC3758382

8. Bochud PY, Bibert S, Kutalicetal Z. 2012. Il 28 b alleles associated with poor Hepatitis Cvirus (hcv) clearance protect against in flammation and fibrosis in patients infected with non-1 hcv genotypes. Hepatology. 55: 384—394.

9. Thomas DI, Thio CI, Martin MP et al. 2009. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature. 461: 798—801.

10. Ge D, Fellay J, Thompson AJ et al. 2009. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 46: 399—401.

11. Marabita F, Aghemo A, De Nicola S et al. 2011. Genetic variation in the interleukin-28B gene is not associated with fibrosis progression in patients with chronic hepatitis C and known date of infection. Hepatology. 54: 1127—1134.

12. Tanaka Y, Nishida N, Sugiyama M et al. 2009. Genome_wide association of IL28D with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet. 41(10): 1105—1109. http://dx.doi.org/10.1038/ng.449; PMid:19749757

13. Sheppard P, Kindsvogel W, Xu W et al. 2003. IL-28, IL-29 and their class 11 cytokine receptor IL-28R. Nat Immunol. 4(1): 63—68. http://dx.doi.org/10.1038/ni873; PMid:12469119

14. Suppiah V, Moldovan M, Ahlenstiel G et al. 2009. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet. 41(10): 1100—1104. http://dx.doi.org/10.1038/ng.447; PMid:19749758

15. Fabris C, Falleti E, Cussigh A et al. 2011. IL-28B rs 12979860 C/T allele distribution in patients with liver cirrhosis role in the course of chronic viral hepatitis and the development of HCC. J Hepatol. 54(4): 716—722. http://dx.doi.org/10.1016/j.jhep.2010.07.019; PMid:21146242

16. Sato M, Kondo M, Teteishi R et al. 2014, Mar. Impact of IL28B genetic on variation on HCV-induced liver fibrosis, inflammation, and steatosis: a meta-analysis. PLoSOne. 17; 9(3): 91822. http://dx.doi.org/10.1371/journal.pone.0091822. eCollection 2014.

17. Rembeck K, Alsio A, Christensen PB et al. 2012. Impact of IL28B-related single nucleotide polymorphisms on liver histopathology in chronic hepatitis C genotype 2 and 3. PloSOne. 7(1): 29370. http://dx.doi.org/10.1371/journal.pone.0029370; PMid:22253715 PMCid:PMC3258245

18. Lander ES, Linton LM, Birren B et al. 2001. Initial sequencing and analysis of the human genome. Nature. 409: 860—921.

19. Agundez JA, Garcia-Martin E, Maestro ML et al. 2012. Relation of IL28B gene polymorphism with biochemical and histological features in hepatitis C virus-induced liver disease. PLoSOne. 7(5): 37998. http://dx.doi.org/10.1371/journal.pone.0037998; PMid:22666430 PMCid:PMC3362530

20. Falleti E, Bitetto D, Fabris C et al. 2011. Role of interleukin 28b rs12979860 c/t polymorphism on the histological outcome of chronic Hepatitis C: Relationship with gender and viral genotype. J Clin Immunology. 31: 891—899.

21. Rauch A, Kutalik Z, Descombes P et al. 2010. Swiss HIV Cohort study. Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology. 138(4): 1338—1347.

22. D'Ambrosio R, Aghemo A, De Francesco R et al. 2014. The association of Il 28b genotype with the histological features of chronic hepatitis C is HCV genotype dependent. Int J Mol Sci. 15(5): 7213—7224. http://dx.doi.org/10.3390/ijms15057213; PMid:24776764 PMCid:PMC4057668

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