Serum HBsAg quantification as noninvasive surrogate parameter of intrahepatocellular cccDNA reduction during antiviral combination therapy with Adefovir and Pegylated interferon alfa–2b

Background: HBV targeted antiviral therapy with adefovir results in a significant reduction of intrahepatic HBV cccDNA (Werle-Lapostolle, Gastroenterology 2004). Pegylated interferon alfa improves serological outcome in HBeAg positive and HBeAg negative patients (Marcellin, New Engl J Med 2004; Janssen, Lancet 2005). This study aimed to determine if quantification of serum HBsAg may act as a surrogate parameter for the reduction of the intrahepatocellular matrix of HBV replication, the cccDNA, during antiviral therapy.

Methods: 26 patients with chronic Hepatitis B received a 48 week course of therapy with 12kDa pegylated interferon alfa 2b 1.5µg/kg bw qw and ADV 10mg qd. Intrahepatocellular cccDNA, serum HBsAg, and serum HBV DNA level were quantified.

Results: Administration of 48 weeks of Peg IFN alfa 2b and adefovir resulted in a strong suppression of intrahepatic cccDNA that positively correlated with a reduction in HBsAg titers, high rates of HBsAg seroconversion, HBeAg seroconversion and loss, respectively.

Conclusions: Reduction of HBsAg demonstrates that antiviral combination therapy reduced the reservoir of transcriptionally active viral cccDNA. Although statistically significant, larger trials are needed to confirm that serum HBsAg quantification may act as a noninvasive predictor of cccDNA reduction during antiviral therapy.

Keywords: Adefovir, HBV, HBsAg Quantifizierung, Hepatitis B, PEG Interferon, cccDNA, combination therapy