Treatment of 171 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with adefovir dipivoxil (ADV) 10 mg over 48 weeks resulted in significant histological, virological, serological, and biochemical improvement compared with placebo. The long-term efficacy and safety of ADV in a subset of these patients was investigated for up to 5 years. Sixty-five patients given ADV 10 mg in year 1 elected to continue in a long-term safety and efficacy study (LTSES). At enrollment, the 65 LTSES patients were a median 34 years old, 83% male, 74% Asian, 23% Caucasian, median baseline serum hepatitis B virus (HBV) DNA 8.45 log 10 copies/mL, and median baseline alanine aminotransferase (ALT) 2.0 ؋ upper limit of normal. At 5 years on study, the median changes from baseline in serum HBV DNA and ALT for the 41 patients still on ADV were 4.05 log 10 copies/mL and ؊50 U/L, respectively. HBeAg loss and seroconversion were observed in 58% and 48% of patients by end of study, respectively. Fifteen patients had baseline and end of follow-up liver biopsies; improvements in necroinflammation and fibrosis were seen in 67% and 60% of these patients, respectively. Adefovir resistance mutations A181V or N236T developed in 13 LTSES patients; the first observation was at study week 195. There were no serious adverse events related to ADV. Conclusion: Treatment with ADV beyond 48 weeks was well tolerated and produced long-term virological, biochemical, serological, and histological improvement. (HEPATOLOGY 2008;48:750-758.) C hronic infection with the hepatitis B virus (HBV) affects an estimated 400 million people worldwide and continues to be an important cause of morbidity and mortality, as well as a source of potential new infections. 1 An estimated one million people die annually of complications of hepatitis B. 2 Chronic hepatitis B (CHB) will require prolonged if not lifelong therapy in a significant number of patients; therefore, long-term safety and efficacy data for antiviral medications are indispensable to guide the risk-benefit assessment for a patient.
Adefovir dipivoxil (ADV) is an oral prodrug of adefovir, a phosphonate nucleotide analog of adenosine monophosphate with activity in vitro against a variety of viruses, including hepadnaviruses such as HBV. Adefovir is metabolized intracellularly to adefovir diphosphate, which is a competitive inhibitor of HBV DNA polymerase that results in termination of the growing DNA chain. In hepatitis B e antigen (HBeAg)-negative CHB patients treated for up to 240 weeks, ADV has been shown to be well tolerated and produced significant improvement in hepatic fibrosis, durable suppression of HBV replication,