Wei, LaiWedemeyer, HeinerLiaw, Yun-FanChan, Henry Lik-YuenPiratvisuth, TeerhaMarcellin, PatrickJia, JidongTan, DemingChow, Wan-ChengBrunetto, Maurizia R.Diago, MoisesMorozov, ViacheslavHe, HuaZhu, YonghongWat, CynthiaSurujbally, BernadetteThompson, Alexander J.2023-11-032023-11-032018-05-22Wei, L. vd. (2018). ''No association between IFNL3 (IL28B) genotype and response to peginterferon alfa-2a in HBeAg-positive or -negative chronic hepatitis B''. Plos One, 13(7).1932-6203https://doi.org/10.1371/journal.pone.0199198https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199198http://hdl.handle.net/11452/34783Background & 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.eninfo:eu-repo/semantics/openAccessScience & technology - other topicsSustained virological responsePegylated interferon-alphaGenetic-variationC virusSpontaneous clearanceHbsag clearanceRibavirinExpressionTherapyPolymorphismsAdultAlanine transaminaseAntiviral agentsAsian continental ancestry groupDNA, viralEuropean continental ancestry groupFemaleGene expressionGenotypeHepatitis B e antigensHepatitis B surface antigensHepatitis B virusHepatitis B, chronicHumansInterferon-alphaInterleukinsMaleMiddle agedPolyethylene glycolsPolymorphism, single nucleotideRecombinant proteinsTreatment outcomeViral loadArticle0004388666000072-s2.0-8505025631013730016335Multidisciplinary sciencesInterferon Type III; Genotype; RibavirinAlanine aminotransferaseHepatitis B surface antigenHepatitis B(e) antigenInterleukin 28BLamivudinePeginterferon alpha2aVirus DNAAlanine aminotransferaseAlpha interferonAntivirus agentHepatitis B surface antigenHepatitis B(e) antigenIL28B protein, humanInterleukin derivativeMacrogolPeginterferon alpha2aRecombinant proteinAdultAlanine aminotransferase blood levelArticleAsianCaucasianChronic hepatitis BControlled studyEthnicityFemaleGenderGene frequencyGene linkage disequilibriumGenetic associationGenotypeHepatitis B virus genotype AHepatitis B virus genotype BHepatitis B virus genotype CHepatitis B virus genotype DHumanIFNL3 geneMajor clinical studyMaleNonhumanRandomized controlled trial (topic)SeroconversionSingle nucleotide polymorphismTreatment durationTreatment responseAntagonists and inhibitorsAsian continental ancestry groupBloodChronic hepatitis BClinical trialDrug effectEthnologyGene expressionGeneticsGenotypeHepatitis B virusImmunologyMiddle agedMulticenter studyRandomized controlled trialTreatment outcomeVirus load