Smaller reduction of hepatitis B virus DNA in liver tissue than in serum in patients losing HBeAg

The prognosis and outcome of treatment for chronic hepatitis B virus (HBV) infection are predicted by levels of HBV DNA in serum. These levels are composed of relaxed circular DNA (rcDNA) and double stranded linear DNA in viral particles, whereas, HBV DNA in liver tissue also can be covalently closed circular DNA (cccDNA) or integrated into the human genome. The aim of this study was to investigate the quantitative relation between HBV DNA in serum and tissue, its change over time and how these markers relate to serum levels of hepatitis B surface antigen (HBsAg). Serum and liver biopsies taken from 15 patients with chronic HBV infection on two occasions during 2.7-11.1 years were analyzed retrospectively. At baseline, the median HBV DNA levels in serum were 7.76 log10 IU/mL in nine hepatitis B e antigen (HBeAg) positive and 3.65 log10 IU/mL in six HBeAg-negative patients. At follow-up, serum HBV DNA, serum HBsAg, and intrahepatic HBV DNA (ihDNA) levels had declined by 4.36, 0.52, and 1.47 log10 units, respectively, in seven patients that lost HBeAg, whereas the corresponding reductions were 0.36, 0.30, and 0.39 log10 units in eight patients with unchanged HBeAg status. We conclude that HBV DNA in liver tissue declined almost 1000 times less than HBV DNA in serum during and after loss of HBeAg. This finding raises the possibility that integrated sequences constitute a significant part of the ihDNA. Alternatively, the greater decline of HBV DNA in serum might be due to yet unknown mechanisms acting downstream of reverse transcription.