Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B

Gastroenterology. 2011 Jan;140(1):132-43. doi: 10.1053/j.gastro.2010.10.011. Epub 2010 Oct 16.


Background & aims: Tenofovir disoproxil fumarate (TDF), a nucleotide analogue and potent inhibitor of hepatitis B virus (HBV) polymerase, showed superior efficacy to adefovir dipivoxil in treatment of chronic hepatitis B through 48 weeks. We evaluated long-term efficacy and safety of TDF monotherapy in patients with chronic hepatitis B who were positive or negative for hepatitis B e antigen (HBeAg(+) or HBeAg(-)).

Methods: After 48 weeks of double-blind comparison of TDF to adefovir dipivoxil, patients who underwent liver biopsy were eligible to continue the study on open-label TDF for 7 additional years; data presented were collected up to 3 years (week 144) from 85% of participants. Primary efficacy end points at week 144 included levels of HBV DNA and alanine aminotransferase, development of resistance mutations, and presence of HBeAg or hepatitis B surface antigen (HBsAg).

Results: At week 144, 87% of HBeAg(-) and 72% of HBeAg(+) patients treated with TDF had levels of HBV DNA <400 copies/mL. Among patients who had previously received adefovir dipivoxil and then received TDF, 88% of the HBeAg(-) and 71% of the HBeAg(+) patients had levels of HBV DNA <400 copies/mL; overall, 81% and 74%, respectively, maintained normalized levels of alanine aminotransferase and 34% had lost HBeAg. Amino acid substitutions in HBV DNA polymerase that are associated with resistance to tenofovir were not detected in any patient. Cumulatively, 8% of HBeAg(+) patients lost HBsAg. TDF maintained a favorable safety profile for up to 3 years.

Conclusions: TDF was safe and effective in the long-term management of HBeAg(+) and HBeAg(-) patients with chronic hepatitis B.

Trial registration: NCT00116805 NCT00117676.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adolescent
  • Adult
  • Alanine Transaminase / blood
  • Antiviral Agents / therapeutic use*
  • Biopsy
  • DNA, Viral / drug effects
  • Drug Resistance, Viral / drug effects
  • Female
  • Follow-Up Studies
  • Hepatitis B e Antigens / analysis
  • Hepatitis B virus / drug effects
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Humans
  • Male
  • Middle Aged
  • Organophosphonates / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Tenofovir
  • Treatment Outcome
  • Virus Replication / drug effects
  • Young Adult


  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B e Antigens
  • Organophosphonates
  • Tenofovir
  • Alanine Transaminase
  • Adenine
  • adefovir dipivoxil

Associated data