PLoS ONE (Jan 2018)

No association between IFNL3 (IL28B) genotype and response to peginterferon alfa-2a in HBeAg-positive or -negative chronic hepatitis B.

  • Lai Wei,
  • Heiner Wedemeyer,
  • Yun-Fan Liaw,
  • Henry Lik-Yuen Chan,
  • Teerha Piratvisuth,
  • Patrick Marcellin,
  • Jidong Jia,
  • Deming Tan,
  • Wan-Cheng Chow,
  • Maurizia R Brunetto,
  • Moisés Diago,
  • Selim Gurel,
  • Viacheslav Morozov,
  • Hua He,
  • Yonghong Zhu,
  • Cynthia Wat,
  • Bernadette Surujbally,
  • Alexander J Thompson

DOI
https://doi.org/10.1371/journal.pone.0199198
Journal volume & issue
Vol. 13, no. 7
p. e0199198

Abstract

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BACKGROUND & AIMS:It has yet to be firmly established whether host IFNL3 (IL28B) genotype influences interferon responsiveness in patients with chronic hepatitis B. We investigated associations between single-nucleotide polymorphisms (SNPs) in the IFNL3 region and response to peginterferon alfa-2a in 701 patients enrolled in three large, randomized, international studies. METHODS:Responses were defined as hepatitis B surface antigen (HBsAg) loss and/or hepatitis B e antigen (HBeAg) seroconversion plus hepatitis B virus (HBV) DNA <2000 IU/ml in HBeAg-positive patients, and HBsAg loss and/or HBV DNA <2000 IU/ml in HBeAg-negative patients (24 weeks after end of treatment). Associations between treatment response and the number of copies of the poor-response allele at three SNPs (rs8099917, rs12980275, rs12979860) were explored with logistic regression models in Asian and white patients. RESULTS:The HBeAg-positive and -negative populations comprised 465 (92% Asian, 50% HBV genotype C) and 236 (79% Asian, 41% HBV genotype C) patients, respectively, and had respective response rates of 26% and 47%. The IFNL3 genotype was strongly associated with ethnicity. There was no association between IFNL3 genotype and treatment response in HBeAg-positive or -negative patients. Independent predictors of treatment response were: sex, HBV DNA level and alanine aminotransferase level in HBeAg-positive Asian patients; age in HBeAg-negative Asian patients; and HBV DNA in HBeAg-negative white patients. CONCLUSIONS:This is the largest analysis to date of associations between IFNL3 genotype and peginterferon response in patients with chronic hepatitis B. The data suggest that IFNL3 polymorphism is not a major determinant of the response to peginterferon alfa-2a in either HBeAg-positive or HBeAg-negative patients.