title: Hepatitis B surface antigen titer is a good indicator of durable viral response after entecavir off-treatment for chronic hepatitis B.
abstract: OBJECTIVE
  Clear indicators for stopping antiviral therapy in chronic hepatitis B (CHB) patients are not yet available. Since the level of hepatitis B surface antigen (HBsAg) is correlated with covalently closed circular DNA, the HBsAg titer might be a good indicator of the off-treatment response. This study aimed to determine the relationship between the HBsAg titer and the entecavir (ETV) off-treatment response.
  
  
  METHODS
  This study analyzed 44 consecutive CHB patients (age, 44.6±11.4 years, mean±SD; men, 63.6%; positive hepatitis B envelope antigen (HBeAg) at baseline, 56.8%; HBV DNA level, 6.8±1.3 log10IU/mL) treated with ETV for a sufficient duration and in whom treatment was discontinued after HBsAg levels were measured. A virological relapse was defined as an increase in serum HBV DNA level of >2000 IU/mL, and a clinical relapse was defined as a virological relapse with a biochemical flare, defined as an increase in the serum alanine aminotransferase level of >2 × upper limit of normal.
  
  
  RESULTS
  After stopping ETV, virological relapse and clinical relapse were observed in 32 and 24 patients, respectively, during 20.8±19.9 months of follow-up. The cumulative incidence rates of virological relapse were 36.2% and 66.2%, respectively, at 6 and 12 months, and those of clinical relapse were 14.3% and 42.3%. The off-treatment HBsAg level was an independent factor associated with clinical relapse (hazard ratio, 2.251; 95% confidence interval, 1.076-4.706;P=0.031). When patients were grouped according to off-treatment HBsAg levels, clinical relapse did not occur in patients with an off-treatment HBsAg level of ≤2 log10IU/mL (n=5), while the incidence rates of clinical relapse at 12 months after off-treatment were 28.4% and 55.7% in patients with off-treatment HBsAg levels of >2 and ≤3 log10IU/mL (n=11) and >3 log10IU/mL (n=28), respectively.
  
  
  CONCLUSIONS
  The off-treatment HBsAg level is closely related to clinical relapse after treatment cessation. A serum HBsAg level of <2 log10IU/mL is an excellent predictor of a sustained off-treatment response in CHB patients who have received ETV for a sufficient duration.
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Han Ah
authors.initials: HA
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Yeon Seok
authors.initials: YS
authors.lastname: Seo
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Seung Woon
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Sang Jung
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Suh
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Young Kul
authors.initials: YK
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Biostatistics, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hyunggin
authors.initials: H
authors.lastname: An
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Yim
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Yeon
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Byun
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Soon Ho
authors.initials: SH
authors.lastname: Um
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; C413685:entecavir; D006147:Guanine; D000410:Alanine Transaminase
keywords: Hepatitis B surface antigen; Hepatitis B virus; Off-treatment; Relapse