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

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.
Competing Interests: LW has received fees for serving as a speaker, consultant, and advisory board member for AbbVie, Bristol-Myers Squibb (BMS), Gilead, Johnson & Johnson (J&J), and GlaxoSmithKline (GSK) within the last 3 years. Additional funding for the study was provided to LW by the China National Science and Technology Major Project for Infectious Diseases Control during the 12th Five-Year Plan Period. HW has received grant/research support from Abbott, BMS, Gilead, Merck, Novartis, Roche, Roche Diagnostics, and Siemens, and has received consulting fees and has been an advisory board and speakers’ bureau member for Abbott, AbbVie, Biolex, BMS, Boehringer Ingelheim, Eiger Pharmaceuticals, Falk Foundation, Gilead, IST, J&J/Janssen-Cilag/Janssen TE, Medgenics, Merck/Schering-Plough, Novartis, Novira, Roche, Roche Diagnostics, Siemens, Transgene, and ViiV. Y-FL has served as an advisory board member for Roche. HL-YC has received fees for serving as a speaker and advisory board member for Roche, BMS, Gilead, Novartis, and MSD, and as a speaker for Echosens and GSK, and has received an unrestricted grant for HBV research from Roche. TP has received grant/research support from BMS, Roche, MSD, Novartis, Fibrogen, and Bayer, and has been a member of advisory boards or speakers’ bureaux for BMS, Roche, MSD, Novartis, and GSK. JJ has received fees for serving as a speaker, consultant, and advisory board member for BMS, MSD, Novartis, and Roche within the last 3 years. MRB has been a member of speakers’ bureaux for BMS, Gilead, Roche, and Janssen, and has been a member of advisory boards for AbbVie, Roche, Gilead, and MSD. MD has been a member of speakers’ bureaux for Roche, MSD, AbbVie, BMS, Gilead, and Janssen. SG has received fees as a member of advisory boards and speakers’ bureaux for Roche, BMS, Gilead, Janssen, and MSD. YZ has been a Genentech/Roche employee and has owned Roche stock and options. HH and CW are employees of Roche and declare stock ownership. BS has received fees for serving as a consultant/contract statistician for Roche, through BStats Solutions Ltd, from March 2013 to the present. AJT has received grant funding from AbbVie, Gilead Sciences, BMS, and Merck, has received consultancy fees from AbbVie, Gilead Sciences, BMS, Roche Diagnostics, Merck, and Spring Bank Pharmaceuticals, and has provided sponsored lectures (national or international) for AbbVie, Roche Diagnostics, Gilead Sciences, BMS, and Merck. The China National Science and Technology Major Project for Infectious Diseases Control during the 12th Five-Year Plan Period provided support in the form of salaries to HH, YZ, CW, and BS. This does not alter our adherence to PLOS ONE policies on sharing data and materials. This study was funded in part by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Peginterferon alfa-2a (PEGASYS®) is marketed worldwide by F Hoffmann-la Roche Ltd, Basel, Switzerland.