title: A double-blind placebo-controlled study of emtricitabine in chronic hepatitis B.
abstract: BACKGROUND
  Emtricitabine is a nucleoside analogue approved for treatment of human immunodeficiency virus 1 with clinical activity against hepatitis B virus (HBV).
  
  
  METHODS
  To compare the safety and efficacy of emtricitabine with placebo in patients with HBV, we conducted a randomized (2:1), double-blind study at 34 sites in North America, Asia, and Europe that enrolled adults between November 2000 and July 2002 who had chronic HBV infection but had never been exposed to nucleoside or nucleotide treatment. Each patient received either 200 mg of emtricitabine (n=167) or placebo (n=81) once daily for 48 weeks and underwent a pretreatment and end-of-treatment liver biopsy. Histologic improvement was defined as a 2-point reduction in Knodell necroinflammatory score with no worsening in fibrosis.
  
  
  RESULTS
  At the end of treatment, 103 (62%) of 167 patients receiving active treatment had improved liver histologic findings vs 20 (25%) of 81 receiving placebo (P<.001), with significance demonstrated in subgroups positive (P<.001) and negative (P=.002) for hepatitis Be (HBe) antigen. Serum HBV DNA readings showed less than 400 copies/mL in 91 (54%) of 167 patients in the emtricitabine group vs 2 (2%) of 81 in the placebo group (P<.001); alanine aminotransferase levels were normal in 65% (109/167) vs 25% (20/81), respectively (P<.001). At week 48, 20 (13%) of 159 patients in the emtricitabine group with HBV DNA measured at the end of treatment had detectable virus with resistance mutations (95% confidence interval, 8%-18%). The rate of seroconversion to anti-HBe (12%) and HBe antigen loss were not different between arms. The safety profile of emtricitabine during treatment was similar to that of placebo. Posttreatment exacerbation of HBV infection developed in 23% of emtricitabine-treated patients.
  
  
  CONCLUSIONS
  In patients with chronic HBV, both positive and negative for HBe antigen, 48 weeks of emtricitabine treatment resulted in significant histologic, virologic, and biochemical improvement.
authors.affiliation: National University Hospital, Singapore.
authors.forename: Seng Gee
authors.initials: SG
authors.lastname: Lim
authors.forename: Tay Meng
authors.initials: TM
authors.lastname: Ng
authors.forename: Nelson
authors.initials: N
authors.lastname: Kung
authors.forename: Zahary
authors.initials: Z
authors.lastname: Krastev
authors.forename: Miroslava
authors.initials: M
authors.lastname: Volfova
authors.forename: Petr
authors.initials: P
authors.lastname: Husa
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Lee
authors.forename: Sing
authors.initials: S
authors.lastname: Chan
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Washington
authors.forename: Amy
authors.initials: A
authors.lastname: Rigney
authors.forename: Jane
authors.initials: J
authors.lastname: Anderson
authors.forename: Elsa
authors.initials: E
authors.lastname: Mondou
authors.forename: Andrea
authors.initials: A
authors.lastname: Snow
authors.forename: Jeff
authors.initials: J
authors.lastname: Sorbel
authors.forename: Richard
authors.initials: R
authors.lastname: Guan
authors.forename: Franck
authors.initials: F
authors.lastname: Rousseau
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D001707:Biopsy, Needle; D004279:DNA, Viral / Q000097:blood; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D000068679:Emtricitabine; D005260:Female; D005838:Genotype; D006510:Hepatitis B Antibodies / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D003841:Deoxycytidine; D000410:Alanine Transaminase; D000068679:Emtricitabine