title: Off-therapy durability of response to entecavir therapy in hepatitis B e antigen-negative chronic hepatitis B patients.
abstract: The optimal duration of nucelos(t)ide analog (Nuc) treatment in hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B virus (HBV) infection is unknown. The Asian Pacific Association for the Study of the Liver (APASL) guidelines recommend that treatment can be discontinued if undetectable HBV-DNA has been documented on three occasions ≥ 6 months apart. This study aimed to test this stopping rule in HBeAg-negative chronic hepatitis B (CHB) patients treated with entecavir (ETV). Ninety-five patients (39 cirrhosis) were treated with ETV for a median of 721 (395-1,762) days before stopping therapy and were then monitored with serum HBV DNA and alanine aminotransferase (ALT) at least every 3 months. Within 1 year after stopping ETV therapy, "clinical relapse" (an episode of ALT elevation >2 × upper limit of normal plus HBV-DNA >2,000 IU/mL) occurred in 43 (45.3%) of the 95 patients. Of the 39 cirrhosis patients, 17 (43.6%) relapsed and one (2.6%) developed decompensation. The median duration until relapse was 230 days (74.4% >6 months). Logistic regression analysis showed that baseline HBV-DNA ≤ 2 × 10(5) IU/mL was the only significant independent factor for sustained response. The 1-year relapse rate was 29% in patients with a baseline HBV DNA ≤ 2 × 10(5) IU/mL versus 53% in those with HBV DNA >2 × 10(5) IU/mL (P = 0.027). For the latter, consolidation therapy >64 weeks reduced the relapse rate to 33.3% in patients without cirrhosis.
  
  
  CONCLUSIONS
  With an overall 1-year relapse rate of 45% and 29% in those with a baseline serum HBV DNA ≤ 2 × 10(5) IU/mL, the APASL stopping rule for HBeAg-negative CHB patients with proper off-therapy monitoring is adequate even in patients with cirrhosis. Consolidation therapy >64 weeks seems more appropriate for those with higher baseline HBV DNA.
authors.affiliation: Liver Research Unit, Linkou Medical Center, Chang Gung Memorial Hospital, Taipei, Taiwan; College of Medicine, Chang Gung University, Taipei, Taiwan.
authors.forename: Wen-Juei
authors.initials: WJ
authors.lastname: Jeng
authors.forename: I-Shyan
authors.initials: IS
authors.lastname: Sheen
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chen
authors.forename: Chao-Wei
authors.initials: CW
authors.lastname: Hsu
authors.forename: Rong-Nan
authors.initials: RN
authors.lastname: Chien
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Chu
authors.forename: Yun-Fan
authors.initials: YF
authors.lastname: Liaw
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood*; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens; C413685:entecavir; D006147:Guanine; D000410:Alanine Transaminase