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

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Gastroenterology. 2010 Oct 15. [Epub ahead of print]

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

Chronic Hepatitis B.

Heathcote EJ, Marcellin P, Buti M, Gane E, de Man RA, Krastev Z, Germanidis G,

Lee SS, Flisiak R, Kaita K, Manns M, Kotzev I, Tchernev K, Buggisch P, Weilert

F, Kurdas OO, Shiffman ML, Trinh H, Gurel S, Snow-Lampart A, Borroto-Esoda K,

Mondou E, J, Sorbel J, Rousseau F.

Abstract

BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF), a nucleotide analogue

and potent inhibitor of hepatitis B virus (HBV) polymerase, showed superior

efficacy to adefovir dipivoxil (ADV) in the treatment of chronic hepatitis B

(CHB) through 48 weeks. We evaluated the long-term efficacy and safety of TDF

monotherapy in patients with CHB that were positive or negative for HB e antigen

(HBeAg+ or HBeAg-).

METHODS: After 48 weeks of double-blind comparison of TDF to ADV, patients who

underwent liver biopsy were eligible to continue study on open-label TDF for 7

additional years; data presented were collected up to 3 years (Week 144), from

85% of participants. The primary efficacy endpoints at week 144 included levels

of HBV DNA and alanine aminotransferase (ALT), development of resistance

mutations, and presence of HBeAg or HBsAg in blood samples.

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

ADV 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 ALT 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.

CONCLUSION: TDF was safe and effective in the long-term management of HBeAg+ and

HBeAg- patients with CHB. TDF continuously suppressed the virus; there was an

increasing percentage of patients with loss of HBsAg up to 3 years, without

development of resistance mutations in HBV polymerase. All studies published in

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AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID: 20955704 [PubMed - as supplied by publisher]