title: On-treatment HBV DNA dynamics predict virological breakthrough in entecavir-treated HBeAg-positive chronic hepatitis B.
abstract: OBJECTIVE
  Virological breakthrough (VBT) could be a manifestation of chronic hepatitis B (CHB) in patients treated with long-term nucleot(s)ide analogues. We aimed to determine the association of on-treatment serum hepatitis B virus (HBV) DNA with VBT in HBeAg-positive CHB patients receiving entecavir (ETV) treatment.
  
  
  METHODS
  A retrospective cohort study, including 162 consecutive patients (95 men and 67 women; mean age, 43.1±13.4 years) with HBeAg-positive CHB treated with ETV for at least 48 weeks between August 2008 and May 2015, was conducted. Univariate and multivariate cox regression analysis were used to identify associations with VBT and clinical factors, including HBV DNA and HBeAg serum status.
  
  
  RESULTS
  Among the 162 ETV-treated HBeAg-positive CHB patients, eighteen patients (11.1%) experienced VBT (VBT group), whereas the other 144 patients were without VBT (non-VBT group). The cumulative rate of HBV DNA < 100 IU/mL in the VBT group and the non-VBT group at week 48 were 44.44% and 70.14%, and at week 96 were 58.33% and 92.56%, respectively (p = 0.015). The cumulative rate of HBeAg seroclearance in the VBT group and non-VBT group at week 48 and week 96 were statistically significant (p = 0.014). Multivariate analysis disclosed that failure to achieve HBeAg seroclearance were the factors significantly associated with VBT.
  
  
  CONCLUSIONS
  Our results demonstrated that on-treatment HBV DNA could probably predict VBT in ETV-treated HBeAg-positive chronic hepatitis B patients. Failure to achieve HBeAg seroclearance was associated with VBT in ETV-treated HBeAg-positive CHB patients. HBV DNA >100IU/mL at 48 weeks is potentially a predictor for VBT.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Yi-Jie
authors.initials: YJ
authors.lastname: Huang
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.|School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chi-Sen
authors.initials: CS
authors.lastname: Chang
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yen-Chun
authors.identifier: http://orcid.org/0000-0002-8993-3039
authors.initials: YC
authors.lastname: Peng
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hong-Zen
authors.initials: HZ
authors.lastname: Yeh
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.|School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Sheng-Shun
authors.initials: SS
authors.lastname: Yang
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism*; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000378:metabolism*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; C413685:entecavir; D006147:Guanine