Long-Term Therapy With Adefovir for HBeAg Negative Chronic Hepatitis B

Past research has demonstrated that treatment with adefovir dipivoxil (Hepsera) for 48 weeks resulted in clinical improvement in patients with hepatitis B "e" antigen (HBeAg) negative chronic hepatitis B. However, this benefit was lost when treatment was discontinued.

As reported in the December 2006 issue of Gastroenterology, an international team of researchers investigated the efficacy, safety, and resistance profile of adefovir treatment for up to 5 years. In this double-blind study, HBeAg negative patients were treated with 10 mg once-daily adefovir or placebo for 48 weeks, followed by adefovir from Week 49 through Week 96. At week 97, 125 patients enrolled in a 144-week open-label follow-on phase, and received adefovir for up to 192 or 240 weeks.

Results

• After 240 weeks on adefovir, 67% of patients had serum HBV DNA levels below 1000 copies/mL.

• After 240 weeks, 69% experienced alanine aminotransferase (ALT) normalization.

• After 192 or 240 weeks of treatment, more than 83% of patients had improvement in liver necro-inflammation.

• 73% had improvement in Ishak fibrosis scores compared with baseline:

- 35% after 48 weeks;
- 55% after 192 weeks;
- 71% after 240 weeks.

• After 240 weeks, the cumulative probability of developing HBV polymerase mutations was 29%.

• However, the cumulative probability of mutations that conferred virological resistance was 20%.

• 11% of subjects had mutations, virological resistance, and ALT elevations.

• Slight elevations in creatinine were confirmed in 4 patients (3%).

Conclusion

In conclusion, the authors wrote, "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."

1/12/07

Reference
S J Hadziyannis, N C Tassopoulos, E J Heathcote, and others. Long-Term Therapy With Adefovir Dipivoxil for HBeAg-Negative Chronic Hepatitis B for up to 5 Years. Gastroenterology 131(6): 1743-1751. December 2006.