Adefovir for Hepatitis B

[Guest guest]

http://www.acpmedicine.com/wnim/acp_0805.htm#L4

Adefovir for Hepatitis B

Adefovir dipivoxil is the prodrug of adefovir, which is a nucleotide

analogue of adenosine monophosphate. Adefovir inhibits HBV DNA polymerase

and reverse transcriptase. It is effective against both wild-type and

lamivudine-resistant HBV and in both HBeAg-positive and HBeAg-negative

chronic hepatitis B.1 Typically, adefovir therapy results in a 3 to 4 log10

drop in serum HBV DNA levels.

In a randomized study involving 515 patients who had HBeAg-positive chronic

hepatitis B, treatment with adefovir, 10 mg daily for 48 weeks, resulted in

a 12% HBeAg seroconversion rate.2 As with lamivudine, the rate of treatment

response is higher in patients who have higher pretreatment alanine

aminotransferase values. Longer-term studies of adefovir are ongoing, and

preliminary results indicate that the HBeAg seroconversion rate increases

after 2 years. Adefovir, particularly at higher doses, may result in some

renal impairment; therefore, it is prudent to periodically monitor renal

function in patients receiving adefovir therapy. Adefovir has not been well

studied in patients with chronic hepatitis B and decompensated cirrhosis.

Adefovir dipivoxil therapy in patients with HBeAg-negative chronic hepatitis

B results in about a 46% biochemical and virologic response rate after 48

weeks and a 51% response rate after 96 weeks. If therapy is stopped after 48

weeks, relapse occurs in more than 90% of patients.3 Development of drug

resistance is much less of a problem with adefovir than with lamivudine.

Resistance to adefovir is seen in about 2% of patients after 2 years and 4%

of patients after 3 years.

1. Lok AS, McMahon BJ: Chronic hepatitis B: update of recommendations. AASLD

Practice Guidelines. Hepatology 39:857, 2004 [PMID 14999707]

2. Marcellin P, Chang TT, Lim SG, et al: Adefovir dipivoxil for the

treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J

Med 348:808, 2003 [PMID 12606735]

3. Hadziyannis SJ, Tassopoulos N, Heathcote EJ, et al: Adefovir dipivoxil

for the treatment of hepatitis B e antigen-negative chronic hepatitis B. N

Engl J Med 348:800, 2003 [PMID 12606734]