PMID- 29221441 OWN - NLM STAT- MEDLINE DCOM- 20180627 LR - 20181113 IS - 1471-230X (Electronic) IS - 1471-230X (Linking) VI - 17 IP - 1 DP - 2017 Dec 8 TI - Time-varying serum gradient of hepatitis B surface antigen predicts risk of relapses after off-NA therapy. PG - 154 LID - 10.1186/s12876-017-0697-3 [doi] LID - 154 AB - BACKGROUND: The serum gradient of hepatitis B surface antigen (HBsAg) varies over time after cessation of nucleos(t)ide analog (NA) treatment in patients with chronic hepatitis B (CHB). The association between the time-varying HBsAg serum gradient and risk of relapse has not been elucidated. METHODS: This multicenter cohort study prospectively enrolled CHB patients who discontinued 3 year-NA treatment. Eligible patients were serologically negative for HBeAg and viral DNA at NA cessation. The participants (n = 140) were followed every 3 months through HBsAg quantification. Virological and clinical relapses were defined as viral DNA levels >2000 IU/mL and alanine aminotransferase (ALT) levels >80 U/mL, respectively. The association of time-varying HBsAg levels with relapses was assessed through a time-dependent Cox analysis. RESULTS: During a median follow-up of 19.9 (interquartile range [IQR], 10.6-25.3) months, virological and clinical relapses occurred in 94 and 49 patients, with a 2-year cumulative incidence of 79.2% (95% confidence interval [CI], 70.9%-86.4%) and 42.9% (95% CI, 34.1%-52.8%), respectively. The serum level of HBsAg was associated with virological (P < 0.001) and clinical (P = 0.01) relapses in a dose-response manner, with adjusted hazard ratios of 2.10 (95% CI, 1.45-3.04) and 2.32 (95% CI, 1.28-4.21). Among the patients (n = 19) whose HBsAg levels ever dropped below 10 IU/mL, only one and three patients subsequently developed clinical and virological relapses. CONCLUSION: The serum gradient of HBsAg measured throughout the off-therapy observation is associated with the subsequent occurrence of virological and clinical relapses in CHB patients who discontinue NA treatment. FAU - Chien, Nai-Hsuan AU - Chien NH AD - Cathay General Hospital, Taipei, Taiwan. AD - School of Medicine, Fu Jen Catholic University, New Taipei, Taiwan. AD - Sijhih Cathay General Hospital, New Taipei, Taiwan. FAU - Huang, Yen-Tsung AU - Huang YT AD - Institute of Statistical Science, Academia Sinica, Taipei, Taiwan. FAU - Wu, Chun-Ying AU - Wu CY AD - Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan. AD - Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. FAU - Chang, Chi-Yang AU - Chang CY AD - School of Medicine, Fu Jen Catholic University, New Taipei, Taiwan. AD - Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan. AD - Division of Gastroenterology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan. FAU - Wu, Ming-Shiang AU - Wu MS AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Kao, Jia-Horng AU - Kao JH AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. AD - Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan. FAU - Mo, Lein-Ray AU - Mo LR AD - Department of Internal Medicine, Tainan Municipal Hospital, Tainan, Taiwan. FAU - Tai, Chi-Ming AU - Tai CM AD - Division of Gastroenterology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan. FAU - Lin, Chih-Wen AU - Lin CW AD - Division of Gastroenterology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan. FAU - Yang, Tzeng-Huey AU - Yang TH AD - Department of Internal Medicine, Lotung Poh-Ai Hospital, Yilan Country, Taiwan. FAU - Lin, Jaw-Town AU - Lin JT AD - School of Medicine, Fu Jen Catholic University, New Taipei, Taiwan. AD - Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan. AD - Division of Gastroenterology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan. FAU - Hsu, Yao-Chun AU - Hsu YC AD - School of Medicine, Fu Jen Catholic University, New Taipei, Taiwan. gatsbyhsu@yahoo.com.tw. AD - Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan. gatsbyhsu@yahoo.com.tw. AD - Division of Gastroenterology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan. gatsbyhsu@yahoo.com.tw. AD - , No.510, Zhongzheng Rd., Xinzhuang Dist, New Taipei City, 24205, Taiwan. gatsbyhsu@yahoo.com.tw. LA - eng GR - 104-GGH-FJU-11/Cathay General Hospital and Fu-Jen University/ GR - EDAHP105019/E-Da Hospital/ GR - TIP104-2/Taipei Pathology Institutes/ PT - Journal Article PT - Multicenter Study DEP - 20171208 PL - England TA - BMC Gastroenterol JT - BMC gastroenterology JID - 100968547 RN - 0 (Antiviral Agents) RN - 0 (DNA, Viral) RN - 0 (Hepatitis B Surface Antigens) RN - EC 2.6.1.2 (Alanine Transaminase) SB - IM MH - Adult MH - Alanine Transaminase/blood MH - Antiviral Agents/administration & dosage/therapeutic use MH - Cohort Studies MH - DNA, Viral/blood MH - Dose-Response Relationship, Drug MH - Female MH - Hepatitis B Surface Antigens/*blood MH - Hepatitis B, Chronic/*drug therapy/*immunology MH - Humans MH - Male MH - Middle Aged MH - Prospective Studies MH - Recurrence MH - Risk Factors MH - Withholding Treatment PMC - PMC5723064 OTO - NOTNLM OT - Chronic hepatitis B OT - Hepatitis B surface antigen quantification OT - Nucleos(t)ide analogs OT - Time-dependent Cox proportion hazards model COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Institutional review boards approved the study protocol (EMRP100-049) in all hospitals for patient recruitment and database establishment. Data analysis specifically for this study was also approved (EMRP-104-082). Written informed consent was obtained from all participants prior to their enrollment. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: YCH has received lecture fees from Bristol-Myers Squibb, Roche, and Gilead Sciences. JHK is a consultant for Abbott, Abbvie, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Johnson & Johnson, Merck Sharp & Dohme, Novartis, and Roche and is on the speaker's bureau for Abbott, Roche, Bayer, Bristol-Myers Squibb, GlaxoSmithKline, and Novartis. JTL has received a research grant from Gilead Sciences in another unrelated study. All other authors have no competing interests to declare. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2017/12/10 06:00 MHDA- 2018/06/28 06:00 PMCR- 2017/12/08 CRDT- 2017/12/10 06:00 PHST- 2017/02/07 00:00 [received] PHST- 2017/11/20 00:00 [accepted] PHST- 2017/12/10 06:00 [entrez] PHST- 2017/12/10 06:00 [pubmed] PHST- 2018/06/28 06:00 [medline] PHST- 2017/12/08 00:00 [pmc-release] AID - 10.1186/s12876-017-0697-3 [pii] AID - 697 [pii] AID - 10.1186/s12876-017-0697-3 [doi] PST - epublish SO - BMC Gastroenterol. 2017 Dec 8;17(1):154. doi: 10.1186/s12876-017-0697-3.