[The efficacy of adefovir dipivoxil monotherapy and the incidence of genotypic resistance to adefovir dipivoxil in patients with lamivudine-resistant chronic hepatitis B infection].

BACKGROUND/AIMS: Adefovir dipivoxil (ADV) is a nucleotide analogue that inhibits wild-type hepatitis B virus (HBV) and lamivudine (LMV)-resistant HBV mutants. The aim of this study was to elucidate the efficacy of ADV monotherapy and the incidence of genotypic resistance to ADV in patients with LMV-resistant chronic HBV infection. METHODS: This study involved 124 patients with chronic HBV infection who had received ADV monotherapy due to the presence of LMV-resistant HBV mutants. The efficacy of ADV was evaluated by the normalization of serum alanine aminotransferase (ALT) level and by the reduction of serum HBV DNA level (with cutoff levels of 2x10(4) IU/mL and 2x10(2) IU/mL). The cumulative rate of HBeAg loss or seroconversion was assessed in HBeAg-positive patients. The development of mutations in the reverse trancriptase region of HBV DNA polymerase was evaluated by direct sequencing analysis during ADV monotherapy. RESULTS: The mean serum HBV DNA level was 5.94 log10IU/mL. At 12 and 24 months after ADV monotherapy, the cumulative rates of serum ALT normalization were 69.4% and 75.5%, respectively, and those of serum HBV DNA reduction were 79.8% and 89.2% for a cutoff level of 2x10(4) IU/mL, and 44.2% and 59.0% for a cutoff of 2x10(2) IU/mL. The mean serum HBV DNA levels at 12 and 24 months were significantly lower than baseline, at 3.24 and 3.04 log10IU/mL, respectively (P<0.001). At 12 months after ADV treatment, the cumulative rates of HBeAg loss and seroconversion were 15.8% and 10.5%, respectively, and the rtN236T and rtA181T/V mutants in HBV DNA polymerase were identified in 25% and 64% of patients, respectively. CONCLUSIONS: Although ADV monotherapy is effective, it leads to a high rate of mutations of HBV DNA reverse transcriptase gene in patients with chronic HBV infections who have LMV-resistant HBV mutants.

[Relationship between serum HBV DNA levels and liver histology in chronic hepatitis B].

BACKGROUND/AIMS: Serum HBV DNA levels are correlated with hepatic histologic activity in chronic HBV infection based on HBeAg. Liver injury may persist, even though HBV DNA are not detected by hybridization assay. This study was to investigate whether serum HBV DNA levels determined by more sensitive quantitative method are correlated with histologic activities in chronic HBV infections. METHODS: This study included 66 chronic HBV infected patients. HBV DNA level was quantified by Cobas Amplicor HBV Monitor. RESULTS: Serum HBV DNA levels in HBeAg-positive patients were significantly higher than HBeAg-negative patients. In HBeAg-positive patients, serum HBV DNA levels showed a significant negative correlation with portal-periportal activity and fibrosis (r=-0.451, -0.446 respectively). AST levels were correlated with lobular, portal-periportal activity and fibrosis (r=0.432, 0.365, 0.301 respectively), whereas ALT levels were related to lobular activity (r=0.294). Elevated AST levels predicted lobular activity, portal-periportal activity, and fibrosis with moderate to severe degree (OR 1.733, 95% CI 1.083-2.775; OR 1.518, 95% 1.028-2.243, p=0.336; OR 17.897, 95% CI 1.517-211.208, p=0.022, respectively). CONCLUSIONS: In HBeAg-positive patients, serum HBV DNA level correlates inversely with histologic activity. On the other hands AST level correlates with histologic activity and the stage of moderate or severe degree.