Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years

BACKGROUND & AIMS: Treatment with adefovir dipivoxil for 48 weeks resulted in clinical improvement in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B that was lost when treatment was discontinued. We investigated the efficacy, safety, and resistance profile of adefovir dipivoxil treatment for up to 240 weeks. METHODS: HBeAg-negative patients were treated double blind with placebo or adefovir dipivoxil 10 mg once daily for 48 weeks, followed by adefovir dipivoxil from week 49 to 96. At week 97, 125 patients enrolled in a 144-week, open-label phase. Patients received adefovir dipivoxil for up to 192 or 240 weeks. RESULTS: Serum hepatitis B virus (HBV) DNA levels were less than 1000 copies per milliliter in 67% of patients, and alanine aminotransferase (ALT) levels normalized in 69% after 240 weeks. After 192 or 240 weeks of treatment, over 83% of patients had improvement in necroinflammation, and over 73% had improvement in fibrosis. Ishak fibrosis scores improved compared with baseline in 35%, 55%, and 71% of patients after 48, 192, and 240 weeks of adefovir dipivoxil, respectively. After 240 weeks, the cumulative probability of HBV polymerase mutations was 29%, but the cumulative probability of mutations with virologic resistance was 20% and of mutations, virologic resistance, and ALT elevations was 11%. Slight elevations in creatinine were confirmed in 4 (3%) patients. CONCLUSIONS: Treatment with adefovir dipivoxil for up to 240 weeks was well tolerated and produced significant, increasing improvement in hepatic fibrosis, durable suppression of HBV replication, normalization of liver enzymes, and delayed development of resistance.