Adefovir Therapy Reduces Hepatitis B Surface Antigen (HBsAg) Levels in Chronic HBV Patients

Results of a prior study demonstrated that 48 weeks of ADV therapy reduced intrahepatic HBV cccDNA by a median of 84% (p=0.002 vs. placebo) in CH-B patients and was correlated with significant reductions in serum and intracellular HBV DNA (Hepatology 2002;36:296A).

Since HBV cccDNA is the transcriptional template for HBsAg, in this study researchers investigated whether reductions in cccDNA translated into reductions in serum HBsAg titer.

The primary aim of this study was to determine if 48 weeks of ADV therapy reduced serum HBsAg titer in CH-B patients. To determine if changes in HBsAg titer correlate with changes in intrahepatic cccDNA levels.

32 patients with HBeAg+ CH-B received 48 weeks of therapy with ADV (n=22) or placebo (n=10). HBsAg was quantified in patient sera by ELISA using the Monolisa AgHBs plus kit (Biorad, France) with purified HBsAg as the standard (Hytest, Finland).

Intrahepatic cccDNA was measured by DNA extraction from liver biopsies and real-time PCR under selective conditions as described previously.

Results

At baseline, patients in the ADV and placebo groups had similar HBsAg titers (medians of 332,599 and 217,378 ng/mL, respectively, p=0.48). After 48 weeks, patients receiving placebo had a median -0.09 log10 change in HBsAg titer (p=0.85 vs. baseline).

Patients receiving ADV therapy demonstrated a median 73% reduction in serum HBsAg (median change of -0.58 log10 ng/mL); this change was significant compared to baseline (p<0.0001) and compared to placebo (p<0.001).

Changes in HBsAg were significantly and positively correlated with changes in intrahepatic cccDNA (p=0.008), total intracellular HBV DNA (p=0.002), and serum HBV DNA (p<0.001).

Conclusions

48 weeks of adefovir dipivoxil therapy results in a significant decrease in serum HBsAg titer in chronic hepatitis B patients.

Changes in HBsAg titer were positively correlated with and similar in magnitude to changes in intrahepatic cccDNA levels providing further evidence that adefovir dipivoxil therapy reduces the reservoir of transcriptionally active cccDNA.

05/17/04

Reference
B Werle and others. Reductions in Serum Hepatitis B Surface Antigen (HBsAg) Occur in Parallel with Reductions in Intrahepatic HBV Covalently Closed Circular (ccc) DNA in Chronic Hepatitis B (CH-B) Patients Receiving Adefovir Dipivoxil (ADV).