Three-Year Efficacy and Safety of Tenofovir Disoproxil Fumarate Treatment for Chronic Hepatitis B

Heathcote E. J. , Marcellin P., Buti M., Gane E., De Man R. A. , Krastev Z., ...More

GASTROENTEROLOGY, vol.140, no.1, pp.132-143, 2011 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 140 Issue: 1
  • Publication Date: 2011
  • Doi Number: 10.1053/j.gastro.2010.10.011
  • Title of Journal : GASTROENTEROLOGY
  • Page Numbers: pp.132-143


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.