title: Randomized, placebo-controlled trial of tenofovir disoproxil fumarate in adolescents with chronic hepatitis B.
abstract: Tenofovir disoproxil fumarate (DF) is highly effective for the suppression of hepatitis B virus (HBV) in chronically infected adults. This study evaluated the safety and efficacy of tenofovir DF in adolescents with chronic hepatitis B (CHB). In this double-blind, placebo-controlled trial, adolescents 12 to <18 years of age with CHB were randomized to tenofovir DF 300 mg (n = 52) or placebo (n = 54) once daily for 72 weeks. The primary endpoint was virologic response (HBV DNA <400 copies/mL) at week 72. One hundred six patients were enrolled; 101 patients completed 72 weeks of treatment. At baseline, 91% of patients were hepatitis B e antigen-positive and 85% had prior exposure to HBV therapy. A virologic response was observed in 89% (46/52) of patients who received tenofovir DF and 0% (0/54) of patients who received placebo (P < 0.001). Treatment response was not affected by prior HBV treatment. Furthermore, no resistance to tenofovir DF developed through week 72. Among patients with an alanine aminotransferase (ALT) level greater than the upper limit of normal at baseline, normalization of ALT occurred in 74% of patients receiving tenofovir DF and 31% of patients receiving placebo (P < 0.001). The rate of grade 3/4 adverse events was higher among patients treated with placebo (24%) than patients treated with tenofovir DF (10%). No patients met the safety endpoint of a 6% decrease in spine bone mineral density at week 72.
  
  
  CONCLUSIONS
  Tenofovir DF therapy in HBV-infected adolescents was well tolerated and highly effective at suppressing HBV DNA and normalizing ALT values in both treatment-naïve adolescents and those with prior exposure to HBV therapy.
authors.affiliation: Division of Gastroenterology and Hepatology, Seattle Children's and University of Washington School of Medicine, Seattle, WA 98105, USA. karen.murray@seattlechildrens.org
authors.forename: Karen F
authors.initials: KF
authors.lastname: Murray
authors.forename: Leszek
authors.initials: L
authors.lastname: Szenborn
authors.forename: Jacek
authors.initials: J
authors.lastname: Wysocki
authors.forename: Stephen
authors.initials: S
authors.lastname: Rossi
authors.forename: Amoreena C
authors.initials: AC
authors.lastname: Corsa
authors.forename: Phillip
authors.initials: P
authors.lastname: Dinh
authors.forename: John
authors.initials: J
authors.lastname: McHutchison
authors.forename: Phillip S
authors.initials: PS
authors.lastname: Pang
authors.forename: Luminita M
authors.initials: LM
authors.lastname: Luminos
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Pawlowska
authors.forename: Jacek
authors.initials: J
authors.lastname: Mizerski
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D002648:Child; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D000068698:Tenofovir; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D000068698:Tenofovir; D000410:Alanine Transaminase; D000225:Adenine