Lai Wei1, Heiner Wedemeyer2, Yun-Fan Liaw3, Henry Lik-Yuen Chan4, Teerha Piratvisuth5, Patrick Marcellin6, Jidong Jia7, Deming Tan8, Wan-Cheng Chow9, Maurizia R Brunetto10, Moisés Diago11, Selim Gurel12, Viacheslav Morozov13, Hua He14, Yonghong Zhu15, Cynthia Wat14, Bernadette Surujbally16, Alexander J Thompson17. 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. 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'Hépatologie and INSERM CRB3/U773, Université Paris-Diderot, Clichy, France. 7. Beijing Friendship Hospital, Capital Medical University, Beijing, China. 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.
Abstract
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.
RCT Entities:
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.
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