单位：[1]Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China,[2]Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany,[3]Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan,中山大学附属第二医院[4]Department of Medicine and Therapeutics, Institute of Digestive Disease and State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China,[5]NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songklanagarind Hospital, Songkhla, Thailand,[6]Service d'HeÂpatologie and INSERM CRB3/U773, Universite Paris-Diderot, Clichy, France,[7]Beijing Friendship Hospital, Capital Medical University, Beijing, China,首都医科大学附属北京友谊医院[8]Xiangya Hospital, Central South University, Changsha, Hunan Province, China,[9]Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore, Singapore,[10]Hepatology Unit, University Hospital of Pisa, Pisa, Italy,[11]Hospital General de Valencia, Valencia, Spain,[12]Department of Gastroenterology, Medical Faculty, Uludag University, Bursa, Turkey,[13]Medical Company Hepatolog, LLC, Samara, Russian Federation,[14]Roche Products Ltd, Welwyn, United Kingdom,[15]Genentech Inc., San Francisco, California, United States of America,[16]BStats Solutions Ltd, Hertfordshire, United Kingdom,[17]St Vincent's Hospital, University of Melbourne, Fitzroy, Victoria, Australia[18]Current address: Roche Innovation Center Shanghai, Pudong, Shanghai, China
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.
基金：
F. Hoffmann-La Roche Ltd, Basel, SwitzerlandHoffmann-La Roche; China National Science and Technology Major Project for Infectious Diseases Control during the 12th Five-Year Plan Period [2012ZX10002003]; AbbVieAbbVie; Bristol-Myers Squibb (BMS)Bristol-Myers Squibb; GileadGilead Sciences; Johnson Johnson (JJ); GlaxoSmithKline (GSK)GlaxoSmithKline; China National Science and Technology Major Project for Infectious Diseases Control during the 12th Five-Year Plan Period; AbbottAbbott Laboratories; BMSBristol-Myers Squibb; MerckMerck & Company; NovartisNovartis; RocheRoche Holding; Roche Diagnostics; SiemensSiemens AG; MSD; Fibrogen; BayerBayer AG; Roche, through BStats Solutions Ltd; Gilead SciencesGilead Sciences; Spring Bank Pharmaceuticals
第一作者单位：[1]Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China,
通讯作者：
推荐引用方式(GB/T 7714)：
Lai Wei,Heiner Wedemeyer,Yun-Fan Liaw,et al.No association between IFNL3 (IL28B) genotype and response to peginterferon alfa-2a in HBeAg-positive or -negative chronic hepatitis B[J].PLOS ONE.2018,13(7):doi:10.1371/journal.pone.0199198.
APA：
Lai Wei,Heiner Wedemeyer,Yun-Fan Liaw,Henry Lik-Yuen Chan,Teerha Piratvisuth...&Alexander J. Thompson.(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)
MLA：
Lai Wei,et al."No association between IFNL3 (IL28B) genotype and response to peginterferon alfa-2a in HBeAg-positive or -negative chronic hepatitis B".PLOS ONE 13..7(2018)
