阿迪福韦对HBV-DNA和HBV基因型效应的试药结果

liver411

(谢谢大家能够帮助大家翻译)

Distribution of HBV Genotypes and Serum HBV DNA Response in Patients in Phase 3 Studies of Hepsera (Adefovir Dipivoxil)

Previous study results suggest that HBV genotype influences the efficacy of interferon alfa in chronic hepatitis B patients and HBV serotype reportedly alters the efficacy and incidence of resistance during Epivir-HBV (lamivudine) therapy.

To evaluate the effect of HBV genotypes on the efficacy of Hepsera (adefovir dipivoxil), investigators analyzed the HBV genotypes from patients in two large Phase III studies of adefovir dipivoxil were analyzed: GS-437 (HBeAg+, chronic hepatitis B) and GS-438 (HBeAg-, presumed precore mutant, chronic hepatitis B). The ethnic and geographic distribution of HBV genotypes as well as the efficacy of ADV 10 mg daily were analyzed in patients stratified by HBV genotype, HBeAg status and ethnicity.

Results of the study were presented at the 53rd AASLD in Boston. Following is a summary review of the study abstract.

Methods: A 1032 nucleotide PCR product from the HBV polymerase gene was sequenced from baseline serum samples (n=694). Genotypes were determined by phylogenetic analyses using DNAstar (v. 4.00) and PHYLIP (v. 3.5c) along with seventy Genbank HBV reference sequences of known genotype. Serum HBV DNA levels were determined by PCR (Roche AmplicorTM). Statistical comparisons were made using SAS (v. 8.1).

Results: Genotypes A (29%), B (20%), C (36%), and D (11%) were common in HBeAg+ patients. Genotype D (62%) was predominant in HBeAg- patients, although genotypes B (17%) and C (13%) were also observed.

Genotypes E, F, and G were rare (< 2% each) in both studies. North American, European, Mediterranean, and Asian/Oceanic study sites each had distinct genotype profiles. Genotypes C (40%) and A (34%) were most common in North America. Genotypes A (40%) and D (35%) were most common in Europe.

Genotype D (83%) was dominant in Mediterranean countries. Genotypes C (46%) and B (42%) were most common in Asia/Oceania. Regardless of study-site location, Asian patients were infected almost exclusively with genotypes B and C (93%) whereas Caucasian patients were infected predominantly with A and D (93%).

Forty-eight weeks of ADV 10 mg therapy resulted in potent reductions in serum HBV DNA in patients across all genotypes (mean changes ranged from -3.4 to -4.2 log10 copies/mL) with no significant differences in inter-genotype responses (p=0.90, Kruskal-Wallis test).

Patients with HBeAg+ and HBeAg- chronic hepatitis B had mean changes in serum HBV DNA of -3.6 and -3.7 log10 copies/mL, respectively; this difference was also not significant (p=0.50, Wilcoxon rank sum test). Asian, Caucasian, and Black patients had mean changes in serum HBV DNA of -3.6, -3.7, and -2.9 log10 copies/mL, respectively; these differences were not significant (p=0.18, Kruskal-Wallis test).

Conclusions: HBV genotypes were asymmetrically distributed with respect to ethnicity, geography, and HBeAg status. There was a stronger correlation between HBV genotype and ethnicity than between HBV genotype and geography.

Forty-eight weeks of ADV 10 mg therapy resulted in significant decreases in serum HBV DNA in chronic hepatitis B patients regardless of HBV genotype, HBeAg status, or ethnicity. In contrast to recent reports for other therapies, there were no significant differences in mean reductions of serum HBV DNA in adefovir dipivoxil-treated patients infected with different genotypes of HBV.

01/17/03

References
C Westland and others. DISTRIBUTION OF HBV GENOTYPES AND SERUM HBV DNA RESPONSE IN 694 PATIENTS IN PHASE 3 STUDIES OF ADEFOVIR DIPIVOXIL. Abstract 839. 53rd AASLD. November 1-5, 2002. Boston, MA. Hepatology 2002: Vol 36 No 4, Pt 2 of 2.

silence

本文得出结论

阿迪福韦对HBV-DNA和HBV基因型效应的试药结果。不同基因型没有区别

48周10mg/天阿迪福韦对所有基因型hbv dna 降低10的3.4次方到4.2次方

Forty-eight weeks of ADV 10 mg therapy resulted in potent reductions in serum HBV DNA in patients across all genotypes (mean changes ranged from -3.4 to -4.2 log10 copies/mL) with no significant differences in inter-genotype responses (p=0.90, Kruskal-Wallis test).