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Adefovir (Hepsera) for Treatment of Patients with Chronic Hepatitis B Resistant to Lamivudine (Epivir)

In a prospective cohort study, 29 participants with lamivudine-resistant HBV were treated with adefovir (Hepsera) alone, while 23 continued lamivudine and added adefovir.

Long-term successful treatment of hepatitis B virus (HBV) infection is limited by the virus' ability to develop resistance to nucleoside/nucleotide analog drugs. Lamivudine (Epivir-HBV) is among the most widely used and least expensive anti-HBV agents, but resistance is common and develops rapidly, especially when used as monotherapy.

As reported in the January 31, 2008 advance online edition of the Journal of Hepatology, Italian investigators compared treatment efficacy, factors predicting response, and HBV mutations in chronic hepatitis B patients with lamivudine resistant virus.

• 55% of patients treated with adefovir monotherapy and 83% of those treated with lamivudine plus adefovir achieved virological response (P > 0.05).
• Response was directly related to baseline HBV viral load, and occurred in 10 patients with baseline HBV DNA < 17,200 IU/ml using both strategies.
• In patients with a higher baseline HBV DNA, virological response was more frequent in those treated with combination therapy (P < 0.05).
• Mutations at position rt181 predicted HBV DNA persistence during therapy.
• Virological rebound occurred in 18% of non-responders while on adefovir monotherapy.

Conclusion

"To achieve a complete virological response and reduce the risk of adefovir-resistant mutants in lamivudine-resistant patients, rescue therapy is preferable at early evidence of genotypic resistance," the authors concluded.

However, "in subjects with a significant viral load, combination therapy is more effective," they added. "The presence of the rt181 mutation is associated with incomplete response."

3/04/08

Reference

S. Gaia, V Barbon V, A Smedile, and others. Lamivudine-resistant chronic hepatitis B: an observational study on adefovir in monotherapy or in combination with lamivudine. Journal of Hepatology. January 31, 2008 [Epub ahead of print].