Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Single Nucleotide Polymorphism of Interferon Lambda-4 Gene is not Associated with Treatment Response to Pegylated Interferon in Thai Patients with Chronic Hepatitis B

  • Limothai, Umaporn (Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University) ;
  • Wasitthankasem, Rujipat (Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University) ;
  • Poovorawan, Yong (Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University) ;
  • Tangkijvanich, Pisit (Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University)
  • Published : 2015.08.03
Download PDF
⟨ Previous Next ⟩

Abstract

The single nucleotide polymorphism (SNP) ss469415590 in the interferon lambda-4 (IFNL4) gene has recently been reported to have an association with treatment response in chronic hepatitis C. However, any importance of the SNP in association with response to pegylated interferon (PEG-IFN) therapy in patients with chronic hepatitis B (CHB) is unclear. We retrospectively analyzed data for Thai patients with CHB treated with PEG-IFN for 48 weeks. Virological response (VR) for HBeAg-positive CHB was defined as HBeAg seroconversion plus HBV DNA level <2,000 IU/mL at 24 weeks post-treatment. VR for HBeAg-negative CHB was defined as an HBV DNA level <2,000 IU/mL at 48 weeks. The SNP was identified by real time PCR using the TaqMan genotyping assay with MGB probes. A total 254 patients (107 HBeAg-positive and 147 HBeAg-negative) were enrolled in the study. The distribution of TT/TT, ${\Delta}G/TT$ and ${\Delta}G/{\Delta}G$ genotypes was 221 (87.0%), 32 (12.6%) and 1 (0.4%), respectively. Patients with non-TT/TT genotypes had significantly higher baseline HBV DNA levels than patients with the TT/TT genotype. In HBeAg-positive CHB, 41.2% of patients with TT/TT genotype versus 50.0% with non-TT/TT genotype achieved VR (P=0.593). In HBeAg-negative CHB, the corresponding figures were 40.3% and 43.5%, respectively (P=0.777). There was no significant correlation between the SNP genotypes and HBsAg clearance in both groups of patients. In summary, ss469415590 genotypes were not associated with response to PEG-IFN in Thai patients with HBeAg-positive and HBeAg-negative CHB.

Keywords

References

  1. Akkarathamrongsin S, Thong VD, Payungporn S, et al (2014). IFNL3 (IL28B) and IFNL4 polymorphisms are associated with treatment response in Thai patients infected with HCV genotype 1, but not with genotypes 3 and 6. J Med Virol, 86, 1482-90. https://doi.org/10.1002/jmv.23957
  2. Bibert S, Roger T, Calandra T, et al (2013). IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction. J Exp Med, 210, 1109-16. https://doi.org/10.1084/jem.20130012
  3. Castera L, Pinzani M, Bosch J (2012). Non invasive evaluation of portal hypertension using transient elastography. J Hepatol, 56, 696-703. https://doi.org/10.1016/j.jhep.2011.07.005
  4. Cheng L, Sun X, Tan S, et al (2014). Effect of HLA-DP and IL28B gene polymorphisms on response to interferon treatment in hepatitis B e-antigen seropositive chronic hepatitis B patients. Hepatol Res, 44, 1000-7. https://doi.org/10.1111/hepr.12284
  5. de Niet A, Takkenberg RB, Benayed R, et al (2012). Genetic variation in IL28B and treatment outcome in HBeAgpositive and-negative chronic hepatitis B patients treated with Peg interferon alfa-2a and adefovir. Scand J Gastroenterol, 47, 475-81. https://doi.org/10.3109/00365521.2011.648952
  6. Gao J, Xie L, Yang WS, et al (2012). Risk factors of hepatocellular carcinoma-current status and perspectives. Asian Pac J Cancer Prev, 13, 743-52. https://doi.org/10.7314/APJCP.2012.13.3.743
  7. Ge D, Fellay J, Thompson AJ, et al (2009). Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature, 461, 399-401. https://doi.org/10.1038/nature08309
  8. Holmes JA, Nguyen T, Ratnam D, et al (2013). IL28B genotype is not useful for predicting treatment outcome in Asian chronic hepatitis B patients treated with pegylated interferonalpha. J Gastroenterol Hepatol, 28, 861-6. https://doi.org/10.1111/jgh.12110
  9. Hoofnagle JH, Doo E, Liang TJ, et al (2007). Management of hepatitis B: summary of a clinical research workshop. Hepatology, 45, 1056-75. https://doi.org/10.1002/hep.21627
  10. Lampertico P, Vigano M, Cheroni C, et al (2013). IL28B polymorphisms predict interferon-related hepatitis B surface antigen seroclearance in genotype D hepatitis B e antigennegative patients with chronic hepatitis B. Hepatology, 57, 890-6. https://doi.org/10.1002/hep.25749
  11. Prokunina-Olsson L, Muchmore B, Tang W, et al (2013). A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet, 45, 164-71. https://doi.org/10.1038/ng.2521
  12. Rauch A, Kutalik Z, Descombes P, et al (2010). Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology, 138, 1338-45. https://doi.org/10.1053/j.gastro.2009.12.056
  13. Sonneveld MJ, Wong VW, Woltman AM, et al (2012). Polymorphisms near IL28B and serologic response to peginterferon in HBeAg-positive patients with chronic hepatitis B. Gastroenterology, 142, 513-20. https://doi.org/10.1053/j.gastro.2011.11.025
  14. Stattermayer AF, Scherzer T, Beinhardt S, et al (2014). Review article: genetic factors that modify the outcome of viral hepatitis. Aliment Pharmacol Ther, 39, 1059-70. https://doi.org/10.1111/apt.12717
  15. Sung JJ, Tsoi KK, Wong VW, et al (2008). Meta-analysis: Treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther, 28, 1067-77. https://doi.org/10.1111/j.1365-2036.2008.03816.x
  16. Suppiah V, Moldovan M, Ahlenstiel G, et al (2009). IL28B is associated with response to chronic hepatitis C interferonalpha and ribavirin therapy. Nat Genet, 41, 1100-4. https://doi.org/10.1038/ng.447
  17. Tanaka Y, Nishida N, Sugiyama M, et al (2009). Genome-wide association of IL28B with response to pegylated interferonalpha and ribavirin therapy for chronic hepatitis C. Nat Genet, 41, 1105-9. https://doi.org/10.1038/ng.449
  18. Tangkijvanich P, Komolmit P, Mahachai V, et al (2010). Comparison between quantitative hepatitis B surface antigen, hepatitis B e-antigen and hepatitis B virus DNA levels for predicting virological response to pegylated interferon-alpha-2b therapy in hepatitis B e-antigen-positive chronic hepatitis B. Hepatol Res, 40, 269-77. https://doi.org/10.1111/j.1872-034X.2009.00592.x
  19. Terczynska-Dyla E, Bibert S, Duong FH, et al (2014). Reduced IFNlambda4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes. Nat Commun, 5, 5699. https://doi.org/10.1038/ncomms6699
  20. Thomas DL, Thio CL, Martin MP, et al (2009). Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature, 461, 798-801. https://doi.org/10.1038/nature08463
  21. Tseng TC, Yu ML, Liu CJ, et al (2011). Effect of host and viral factors on hepatitis B e antigen-positive chronic hepatitis B patients receiving pegylated interferon-alpha-2a therapy. Antivir Ther, 16, 629-37. https://doi.org/10.3851/IMP1841
  22. Wu H, Zhao G, Qian F, et al (2015). Association of IL28B polymorphisms with peginterferon treatment response in Chinese Han patients with HBeAg-positive chronic hepatitis B. Liver Int, 35, 473-81. https://doi.org/10.1111/liv.12491
  23. Zhang Q, Lapalus M, Asselah T, et al (2014). IFNL3 (IL28B) polymorphism does not predict long-term response to interferon therapy in HBeAg-positive chronic hepatitis B patients. J Viral Hepat, 21, 525-32. https://doi.org/10.1111/jvh.12177

Cited by

  1. rs368234815 and rs117648444 variants predict off-treatment HBsAg seroclearance in IFN-treated HBeAg-negative chronic hepatitis B patients pp.14783223, 2018, https://doi.org/10.1111/liv.13526