title: Low incidence of hepatitis B e antigen seroconversion in patients treated with oral nucleos(t)ides in routine practice.
abstract: OBJECTIVE
  Treatment end-point of therapy for patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) includes HBeAg seroconversion, which ranges from 15% to 22% after 1 year of oral nucleos(t)ides according to clinical trials. Our goal was to determine the incidence and predictors of HBeAg seroconversion in such patients in routine clinical practice because they may differ than reported rates.
  
  
  METHODS
  We conducted a retrospective cohort study of 333 consecutive treatment-naïve HBeAg-positive patients who were treated for CHB between 1/2000 and 6/2010 at three gastroenterology and liver clinics in the USA. Primary study end-point was HBeAg seroconversion-loss of HBeAg and antibody to HBeAg (anti-HBe) development.
  
  
  RESULTS
  The majority of patients were Asian (96%). Median treatment duration prior to HBeAg seroconversion was 50 (range 26-52) weeks. Of the 333 study patients, 25% received lamivudine, 16% adefovir, 51% entecavir, and 8% tenofovir. HBeAg seroconversion at month 12 was 8.2%. On multivariate analysis inclusive of age, gender, and antiviral agents, independent predictors for HBeAg seroconversion at month 12 were hepatitis B virus DNA < 7.5 log10  IU/mL (hazard ratio [HR] = 2.59 [1.04-6.44]), P = 0.041) and alanine transaminase (ALT) > 1.5 × upper normal limit (HR = 2.86 [1.05-7.81], P = 0.040), but not the choice of nucleos(t)ides.
  
  
  CONCLUSIONS
  The HBeAg seroconversion rate seen in clinical settings for oral nucleos(t)ides appears much lower than those reported in pivotal trials, especially in patients with lower ALT and higher HBV DNA levels. HBeAg-positive patients should be counseled about the high possibility of the long treatment duration required to achieve recommended treatment end-points.
authors.affiliation: Pacific Health Foundation, California, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Lin
authors.forename: Nghiem B
authors.initials: NB
authors.lastname: Ha
authors.forename: Anne
authors.initials: A
authors.lastname: Liu
authors.forename: Huy N
authors.initials: HN
authors.lastname: Trinh
authors.forename: Huy A
authors.initials: HA
authors.lastname: Nguyen
authors.forename: Khanh K
authors.initials: KK
authors.lastname: Nguyen
authors.forename: Aijaz
authors.initials: A
authors.lastname: Ahmed
authors.forename: Emmet B
authors.initials: EB
authors.lastname: Keeffe
authors.forename: Ruel T
authors.initials: RT
authors.lastname: Garcia
authors.forename: Gabriel
authors.initials: G
authors.lastname: Garcia
authors.forename: Mindie H
authors.initials: MH
authors.lastname: Nguyen
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage; D004279:DNA, Viral / Q000378:metabolism; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D005260:Female; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009711:Nucleotides / Q000008:administration & dosage*; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D009711:Nucleotides