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

EJ Heathcote, P Marcellin, M Buti, E Gane, Rob de Man, Z Krastev, G Germanidis, SS Lee, R Flisiak, K Kaita, M Manns, I Kotzev, K Tchernev, P Buggisch, F Weilert, OO Kurdas, ML Shiffman, H Trinh, S Gurel, A Snow-LampartK Borroto-Esoda, E Mondou, J Anderson, J Sorbel, F Rousseau

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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.
Original languageUndefined/Unknown
Pages (from-to)132-143
Number of pages12
Issue number1
Publication statusPublished - 2011

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  • EMC MM-04-20-02-A

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