874 and P = 0.005 for the HBeAg-positive group and r = 0.732 and P = 0.003 for the HBeAg-negative group), and no correlation was found between http://www.selleckchem.com/products/dorsomorphin-2hcl.html cccDNA and either intrahepatic rcDNA levels (r = 0.595 and P = 0.1 for the HBeAg-positive group and r = 0.336 and P = 0.2 for the HBeAg-negative group) or serum viral titers (r = 0.659 and P = 0.07 for the HBeAg-positive group and r = 0.530 and P = 0.07 for the HBeAg-negative group). In addition, for all groups and subgroups of patients, we evaluated whether serum HBsAg concentrations correlated directly with intrahepatic amounts of HBV DNA. For both HDV-positive and HDV-negative groups of patients and their HBeAg-positive and HBeAg-negative subgroups, we found no correlation between HBsAg concentrations and either intrahepatic HBV DNA or cccDNA amounts.

Comparisions between HBeAg-positive and HBeAg-negative subgroups of HDV-positive and HDV-negative patients are provided as supplimental material. Analysis of HBV BCP and PC region variability. To evaluate whether mutations in the PC and BCP regions of HBV might have any influence on viral replication and transcription, cccDNA molecules from liver biopsy specimens were analyzed by direct sequencing. Of interest, 5 of the 21 (23.8%) HDV-positive and none of the HDV-negative patients (P = 0.01) carried major HBV populations with large deletions (ranging from 45 to 228 bp) in the BCP and PC regions (Fig. (Fig.5).5). The presence of such deletions was associated with lower viremia levels (r = ?0.458; P = 0.04).

However, the previously reported statistical significances obtained by comparing HDV-positive and HDV-negative patients were maintained when these 5 patients were excluded from the analysis. Among the remaining 16 HDV-positive AV-951 patients, 5 (31%) were infected with HBV strains carrying the G1986A nucleotide substitution, introducing a stop codon in the PC region, and 4 of them also had a double BCP mutation at nucleotide positions 1762 and 1764. The presence of PC and/or BCP mutations showed no association with serum or intrahepatic HBV DNA levels. Major HBV populations from 12 (54%) of the 22 HDV-negative patients (2 HBeAg-positive and 10 HBeAg-negative patients) carried mutations in the BCP/PC regions. Notably, the presence of such mutations in the HBeAg-negative subgroup was associated with higher HBV DNA amounts in both serum (r = 0.808; P = 0.003) and the liver (r = 0.866; P = 0.001). FIG. 5. Alignment of HBV DNA nucleotide sequences corresponding to the basal core promoter region and precore region for wild-type (WT) HBV genotype D and the dominant viral populations of 5 HDV-infected patients (2D, 8D, 12D, 13D, and 16D). The transcription …