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1868Hepatitis B Core Related Antigen Levels Are Associated With Response To ETV and PEG-IFN Treatment In HBeAg-Positive Chronic Hepatitis B PatientsWillem Pieter Brouwer1, Milan J. Sonneveld1, Qing Xie2, Qing Zhang3, Fehmi Tabak4, Adrian Streinu-cercel5, Jiyao Wang6, Gertine van Oord1, Thomas Vanwolleghem1, Suzan D. Pas7, Robert J. de Knegt1, Andre Boonstra1, Bettina E. Hansen1,8, Harry L. Janssen9,1;1Gastroenterology & Hepatology, Erasmus Medical Center Rotterdam, Rotterdam, Netherlands; 2Infectious Diseases, Ruijin Hospital, Jiaotong University, Shanghai, China; 3Gastroenterology and Hepatology, Shanghai Public Health Center, Fu Dan University, Shanghai, China; 4Cerrahpasa Medical Faculty, Istanbul, Turkey; 5National Institute of Infectious Disease, Bucharest, Romania; 6Gastroenterology and Hepatology, Zhong Shan Hospital, Fu Dan University, Shanghai, China; 7Viroscience, Erasmus Medical Center Rotterdam, Rotterdam, Netherlands; 8Department of Public Health, Erasmus MC University Medical Center, Rotterdam, Netherlands; 9Toronto Center for Liver Disease, Toronto Western and General Hospital, University Health Network, Toronto, ON, CanadaBackground. Hepatitis B core related antigen (HBcrAg) is a new marker which is a combined measure of the core proteins HBeAg, HBcAg and p22cr, and correlates with intrahe-patic covalently closed circular DNA. Serum HBcrAg levels may therefore be associated with response to antiviral therapy. Methods. We studied HBeAg-positive patients treated within an international randomized trial (ARES), in which all patients were treated with ETV (0.5mg/day) from w0-24, and randomized to either PEG-IFN add-on from w24-48 (n=85), or to ETV-monotherapy continuation (n=90). Response was defined as HBeAg-loss with HBV DNA<200IU/ml. Only responders at w48 stopped ETV at w72. All patients were followed until w96. Serum HBcrAg was measured using the Lumipulse® G HBcrAg (Fujirebio Europe). Results. At w96, response was achieved in 31% vs. 20% of patients assigned PEG-IFN add-on vs. monotherapy respectively. Lower HBcrAg levels at w0 were associated with response to ETV (OR 0.5, 95%CI:0.3-0.8, p<0.001), but not to PEG-IFN add-on (OR 0.9, 95%CI:0.5-1.6, p=0.678). At w96 more HBcrAg decline was observed among responders (−2.6 vs -2.0 log U/mL for monotherapy and −3.5 vs −2.0 log U/mL for add-on, both p<0.001), with more decline for responders to add-on vs. monotherapy (p=0.010; figure). Lower HBcrAg levels at w48 were associated with HBsAg levels <1000IU/mL at w96 (OR 0.5, 95%CI:0.3-0.8, p=0.002). By Bland-Altman analysis, agreement between HBeAg and HBcrAg measurements at w0 was close (mean difference -3.1×10-6 Log U/mL, 95%CI:-0.9 - 0.9), with comparable on-treatment results obtained for w12-96. Conclusion. On-treatment HBcrAg decline is associated with response to both ETV monotherapy and ETV+PEG-IFN add-on therapy, with most prominent declines observed during PEG-IFN. HBcrAg and HBeAg measurements seemed to follow similar on-treatment dynamics.
Disclosures:
Milan J. Sonneveld - Advisory Committees or Review Panels: Roche; Speaking and Teaching: Roche, BMS
Suzan D. Pas - Grant/Research Support: the Virgo consortium, funded by the Dutch government (FES0908), the Netherlands Genomics Initiative (NGI) project number 050-060-452, the European Community Seventh Framework Programme (FP7/2007-2013) under project EMPERIE (grant agreement no. 223498]
Robert J. de Knegt - Advisory Committees or Review Panels: MSD, Roche, Norgine, Janssen Cilag; Grant/Research Support: Gilead, MSD, Roche, Janssen Cilag, BMS; Speaking and Teaching: Gilead, MSD, Roche, Janssen Cilag
Andre Boonstra - Grant/Research Support: BMS, Janssen Pharmaceutics, Merck, Roche
Harry L. Janssen - Consulting: Abbott, Bristol Myers Squibb, Debio, Gilead Sciences, Merck, Medtronic, Novartis, Roche, Santaris; Grant/Research Support: Anadys, Bristol Myers Squibb, Gilead Sciences, Innogenetics, Kirin, Merck, Medtronic, Novartis, Roche, Santaris
The following people have nothing to disclose: Willem Pieter Brouwer, Qing Xie, Qing Zhang, Fehmi Tabak, Adrian Streinu-cercel, Jiyao Wang, Gertine van Oord, Thomas Vanwolleghem, Bettina E. Hansen
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