title: Efficacy of entecavir in chronic hepatitis B patients with mildly elevated alanine aminotransferase and biopsy-proven histological damage.
abstract: Current guidelines for management of chronic hepatitis B recommend treatment for patients presenting with elevated hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) >2 x upper limit of normal (ULN) or histological evidence of liver disease. Retrospective analyses have demonstrated that significant hepatic necroinflammation and fibrosis were present in a substantial proportion of patients with ALT 1 to 2 x ULN. To assess therapeutic efficacy in this clinical setting, we retrospectively examined treatment endpoints among the subset of nucleoside-naïve chronic hepatitis B (CHB) patients treated in phase 3 clinical trials of entecavir who had both screening and baseline serum ALT 1.3 to 2 x ULN. A total of 1347 patients were randomized to treatment with entecavir or lamivudine. Three hundred thirty-six patients, constituting 25% of the total study population, had screening and baseline ALT 1.3 to 2 x ULN. Clinically significant necroinflammation (Knodell necroinflammation score > or =7) was observed in 60% and 72% of hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients, respectively, whereas marked fibrosis (Ishak fibrosis score > or =4) was observed in 8% and 15% of HBeAg-positive and HBeAg-negative patients, respectively. Among entecavir-treated HBeAg-negative patients, the proportions of patients achieving histological improvement, HBV DNA <300 copies/mL, and ALT normalization were similar between patients with mildly elevated ALT and those with ALT >2 x ULN. However, entecavir-treated HBeAg-positive patients with mildly elevated ALT had lower response rates for histological improvement, HBV DNA less than 300 copies/mL, ALT normalization, and HBeAg seroconversion than those with ALT greater than 2 x ULN.
  
  
  CONCLUSIONS
  This retrospective analysis demonstrated that HBeAg-negative CHB patients treated with entecavir responded similarly irrespective of baseline ALT level. However, HBeAg-positive patients with mildly elevated ALT responded less well to treatment with entecavir than did those with ALT greater than 2 x ULN.
authors.affiliation: National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: I-Chin
authors.initials: IC
authors.lastname: Wu
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lai
authors.forename: Steven-Huy Bui
authors.initials: SH
authors.lastname: Han
authors.forename: Kwang-Hyup
authors.initials: KH
authors.lastname: Han
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Gordon
authors.forename: You-Chen
authors.initials: YC
authors.lastname: Chao
authors.forename: Chee-Kiat
authors.initials: CK
authors.lastname: Tan
authors.forename: William
authors.initials: W
authors.lastname: Sievert
authors.forename: Tawesak
authors.initials: T
authors.lastname: Tanwandee
authors.forename: Dong
authors.initials: D
authors.lastname: Xu
authors.forename: Boon-Leong
authors.initials: BL
authors.lastname: Neo
authors.forename: Ting-Tsung
authors.initials: TT
authors.lastname: Chang
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000032:analysis; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008099:Liver / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; C413685:entecavir; D006147:Guanine; D000410:Alanine Transaminase