Hepatitis B : Safety of Tenofovir

Safety of tenofovir disoproxil fumarate treatment for chronic hepatitis


Tenofovir disoproxil fumarate, a nucleotide analogue and potent inhibitor of hepatitis B virus polymerase, showed superior efficacy to adefovir dipivoxil in treatment of chronic hepatitis B through 48 weeks.

Dr Jenny Heathcote and colleagues evaluated long-term efficacy and safety of tenofovir disoproxil fumarate monotherapy in patients with chronic hepatitis B who were positive or negative for hepatitis B e antigen.

After 48 weeks of double-blind comparison of tenofovir disoproxil fumarate to adefovir dipivoxil, patients who underwent liver biopsy were eligible to continue the study on open-label tenofovir disoproxil fumarate for 7 additional years.
Data presented were collected up to 3 years from 85% of participants.
8% of hep B antigen-positive patients lost hep B surface antigen

Gastroenterology
Primary efficacy end points at week 144 included levels of Hepatitis B virus DNA and alanine aminotransferase, development of resistance mutations, and presence of hepatitis B antigen or hepatitis B surface antigen.

At week 144, 87% of hepatitis B antigen, and 72% of hepatitis B antigen-positive patients treated with tenofovir disoproxil fumarate had levels of hepatitis B virus DNA less than 400 copies/mL.
Among patients who had previously received adefovir dipivoxil and then received tenofovir disoproxil fumarate, 88% of the hepatitis B e antigen-negative, and 71% of the hepatitis B e antigen-positive patients had levels of hepatitis B virus DNA less than 400 copies/mL.
Overall, 81% and 74%, respectively, maintained normalized levels of alanine aminotransferase and 34% had lost hepatitis B antigen.

Amino acid substitutions in hepatitis B virus DNA polymerase that are associated with resistance to tenofovir were not detected in any patient.
Cumulatively, 8% of hepatitis B antigen-positive patients lost hepatitis B surface antigen.
Tenofovir disoproxil fumarate maintained a favorable safety profile for up to 3 years.
Dr Heathcote's team concludes, "Tenofovir disoproxil fumarate was safe and effective in the long-term management of hepatitis B e antigen-positive and hepatitis B e antigen−negative patients with chronic hepatitis B."
Gastroenterology 2011: 140(1): 132-4314 January 2011