3]) in HDV-positive and selleckchem HDV-negative patients (Fig. 4B and C). In addition, although statistical significance was not achieved, it has to be pointed out that the ratio of pre-S/S RNA to cccDNA molecules was almost 3-fold higher in HDV-positive than in HDV-negative patients (Fig. (Fig.4B),4B), justifying the significantly larger amounts of HBsAg per cccDNA molecule observed in HDV-positive patients. Finally, the evaluation of the ratio of pgRNA to total HBV RNA revealed a significantly smaller proportion of pregenome molecules (0.1% [range, 0.01% to 4%] versus 0.8% [range, 0.08% to 14%]; P = 0.02) in HDV-positive patients. FIG. 2. Serum and intrahepatic amounts of HBV DNA differ significantly between patients with and without HDV infection.

Median levels of serum HBV DNA (A), intrahepatic HBV rcDNA (B), and HBV cccDNA (C) are shown for HDV-negative and HDV-positive patients. Dots … FIG. 3. Median levels of HBsAg production in HDV-negative and HDV-positive patients. Dots represent single patient measurements. The median is indicated with a long line, and the 25th and 75th percentiles are indicated with error bars. FIG. 4. HBV cccDNA transcription and replicative activities appear to be disconnected in HDV-infected patients. Serum HBsAg (A), intrahepatic pre-S/S RNA (B), and pgRNA (C) concentrations were normalized to cccDNA amounts in the livers of corresponding patients … Correlations between different variables in HDV-positive and HDV-negative patients. In HDV-positive patients, intrahepatic HDV RNA levels showed significant correlations with both serum HDV RNA (r = 0.

569; P = 0.01) and HBV cccDNA (r = 0.595; P = 0.009) levels. However, no significant association was found between serum or intrahepatic HDV RNA concentrations and HBsAg levels, as well as serum and intrahepatic HBV DNA amounts. In addition, HBV DNA measured in the sera of these patients showed no correlation with concentrations of HBsAg (r = 0.329; P = 0.1), intrahepatic HBV DNA (r = 0.173; P = 0.4), or cccDNA (r = 0.205; P = 0.3), whereas a significant correlation was found between intrahepatic HBV DNA and cccDNA amounts (r = 0.438; P < 0.04). When the HDV-positive/HBeAg-negative subgroup of patients was analyzed separately, a significant correlation was found only between intrahepatic HBV DNA and cccDNA amounts (r = 0.577; P < 0.01).

For the HDV-positive/HBeAg-positive subgroup, the correlation between variables could not be evaluated because of the small number of patients included in it. For HDV-negative patients, highly significant correlations Carfilzomib were found between amounts of cccDNA and both intrahepatic rcDNA levels (r = 0.76; P < 0.0001) and serum HBV DNA levels (r = 0.818; P < 0.0001) and between intrahepatic rcDNA and serum HBV DNA levels (r = 0.83; P < 0.0001). However, different results were obtained when the HBeAg-positive and HBeAg-negative patients of the HDV-negative group were evaluated separately.