HBV Genotype and Baseline Viral Load Predict Response to Adefovir (Hepsera) in Lamivudine-resistant Chronic Hepatitis B Patients

Lamivudine (3TC; Epivir) is an inexpensive and widely used treatment for chronic hepatitis B, but the development of drug resistance limits its long-term benefits.

As reported in the September 2007 Journal of Hepatology, Spanish researchers aimed to determine the factors associated with virological response, hepatitis B "e" antigen (HBeAg) loss, and emergence of adefovir-related resistance mutations in adefovir-treated patients with pre-existing lamivudine resistance.

The study included 54 chronic hepatitis B patients with lamivudine-resistant HBV; 46% were HBeAg positive. Participants were treated with either adefovir monotherapy (n=28) or adefovir plus lamivudine (n=26) for an average of about 30 months.

Results

• 38 patients (70.4%) achieved virological response, defined as HBV DNA levels <104 copies/mL within the first 12 months of treatment.

• 6 of 25 initially HBeAg positive patients (24%) experienced HBeAg loss and 20% seroconverted to anti-HBe status.

• 8 patients (14.8%) developed adefovir-related resistance mutations.

• In a multivariate analysis, female sex (HR 0.20; P=0.018), HBeAg negative status at baseline (HR 0.37; P=0.040), and low baseline HBV DNA (HR 0.65; P=0.027) were independent predictors of virological response.

• Low baseline HBV DNA (HR 0.36; P=0.095) and HBV genotype D (HR 0.06; P=0.037) were independent predictors of HBeAg loss.

Conclusion

"Adefovir therapy suppresses viral replication in more than 70% of lamivudine-resistant patients," the authors concluded. "Factors associated with virologic response are female gender, HBeAg negative status and low baseline serum HBV DNA levels. Genotype D HBV infection and low baseline HBV-DNA levels independently predict HBeAg loss."

10/12/07

Reference
M Buti, I Elefsiniotis, R Jardi, and others. Viral genotype and baseline load predict the response to adefovir treatment in lamivudine-resistant chronic hepatitis B patients. Journal of Hepatology 47(3): 366-372. September 2007.