Efficacy and safety of adefovir dipivoxil 20mg daily in HBeAg-positive patients with lamivudine-resistant hepatitis B virus and a suboptimal virological response to adefovir dipivoxil 10mg daily.

摘要

BACKGROUND/AIMS: Some patients receiving adefovir at the approved dose of 10mg daily for chronic hepatitis B have a "suboptimal" virological response characterized by a slow and moderate decrease in viral replication. METHODS: We assessed the efficacy and safety of adefovir 20mg daily in patients with hepatitis B e antigen-positive chronic hepatitis B resistant to lamivudine and a suboptimal virological response to adefovir 10mg daily add-on. RESULTS: No amino acid substitutions known to confer adefovir resistance were found in these patients. In the five treated patients, the switch from 10mg to 20mg of adefovir daily significantly improved antiviral efficacy (-1.78+/-0.28 log international units/mL versus -3.73+/-0.51 log international units/mL, respectively, p=0.0039), and alanine aminotransferase levels normalized in all but one of the patients. No signs of renal dysfunction occurred. CONCLUSIONS: These results suggest: (i) that suboptimal responses to adefovir 10mg daily are due to underdosing; and (ii) that increasing the adefovir dose to 20mg daily is beneficial and safe in patients with lamivudine-resistant HBV and a suboptimal response to adefovir 10mg daily, especially when alanine aminotransferase levels are elevated and/or the liver disease is severe or rapidly progressive. Careful monitoring of renal function is necessary.