A double-blind randomized trial of adefovir dipivoxil in Chinese subjects with HBeAg-positive chronic hepatitis B

Abstract

Four hundred and eighty Chinese subjects with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) were enrolled in a multicenter, double-blind, randomized, placebo-controlled study of adefovir dipivoxil (ADV) 10 mg once daily. There was a significant difference in reduction of serum hepatitis B virus (HBV) DNA after 12 weeks between subjects who received ADV and those who received the placebo (3.4 and 0.1 log 10 copies/mL, respectively, P < .001). Further reductions in serum HBV DNA and increases in the proportion of subjects with an HBV DNA level of at most 10 5 copies/mL, with HBV DNA undetectable, and with ALT normalization were observed in ADV-treated subjects at week 52 (median HBV DNA reduction of 4.5 log 10 copies/mL, 67% with HBV DNA < 10 5 copies/mL, 28% with HBV DNA undetectable, and 79% with ALT normalization). Subjects who initially received ADV lost some treatment benefit after being rerandomized to the placebo in week 40. Subjects with YMDD mutant HBV at baseline had virological, biochemical, and serological responses to treatment that were similar to those of subjects with wild-type HBV. The incidence of clinically adverse events was similar in nature and severity between the treatment groups, and there was no evidence of renal toxicity. No adefovirrelated HBV mutations were identified. In conclusion, treatment with ADV 10 mg daily over 52 weeks was safe and effective in Chinese subjects with HBeAg-positive CHB and did not lead to the emergence of drug resistance. The study is continuing for an additional 4 years with all subjects on open-label ADV 10 mg daily. (HEPATOLOGY 2006;44:108-116.)

Hepatitis B Virus Genotype-Associated Variability in Antiviral Response to Adefovir Dipivoxil Therapy in Chinese Han Population

“…Multinational placebo-controlled clinical trials in HBeAg-positive and negative subjects showed biochemical, virological, and histological improvement. A 52-week ADV treatment resulted in 20% seroclearance of HBeAg, 28% clearance of serum HBV-DNA and 79% with ALT normalization in Chinese cohort (Zeng et al 2006). In this study, our data showed that HBV-DNA seroclearance (41.8% vs 34.6%, p < 0.05) and HBV-DNA reduction (3.6log 10 vs 3.1log 10 , p < 0.05) were significantly higher in genotype B than those in genotype C at week 48 on ADV therapy.…”

Eficácia do adefovir dipivoxil, entecavir e telbivudina para o tratamento da hepatite crônica B: revisão sistemática

“…Dose mais elevada de ADV (30mg) demonstrou resultados terapêuticos melhores que dose de 10mg, entretanto foram observados níveis de creatinina maiores que 0,5mg/ dL para a dose de 30mg (8%). O perfil de segurança do ADV foi semelhante ao placebo 7,13 .…”

Lamivudine for chronic hepatitis B: a brief review

“…In addition, the long-term efficacy of lamivudine is limited by the frequent emergence of drug-resistant HBV mutants [5][6][7]. Adefovir is a nucleotide analogue associated with a low frequency of resistance; however, its antiviral efficacy is not optimal [8,9].…”