慢性乙型肝炎抗病毒治疗的现状及进展创新.ppt

Primary endpoint was improvement in histology Secondary 终点 Change from baseline in HBV DNA by PCR assay HBeAg loss and seroconversion (in HBeAg+ study) Change from baseline in ALT and normalization Improvement in fibrosis Safety At one year in both eAg+ and eAg- patients adefovir resulted in significant improvements in liver histology compared to placebo With increasing treatment duration, ADV therapy increases or maintains improvement in Significant and sustained 血清 HBV DNA reductions and % patients with HBV DNA undetectable by PCR-based assay ALT reduction and normalization HBeAg loss and seroconversion (HBeAg+ Study) . = A comprehensive resistance surveillance programme has been conducted, including 5 studies: 437, 438, 460i,435 and 412 extended. Patient population covers: HBeAg+/-, co-infected with HIV, LAM-R. Total 629 at w48. Resistance is delayed and infrequent: Year 1 (n=629) 0%; Year 2 (n=293) 2%; Year 3 (n=167) 3.9% Added this slide Took out word double blind since it adds little For patients continued on lamivudine, noted in beige, there was no change in serum HBV DNA over the 52 weeks in study 465 and 48 weeks in study 461. As in the pivotal studies, a rapid ~ 2 log decline in serum HBV DNA is observed in the ADV arms. The reductions continue to week 52 in study 465 and week 48 in study 461. The HBV DNA reductions in ADV arms are statistically significant. ADV monotherapy shows an important contribution in controlling active viral replication in patients who are failing lamivudine treatment, and there is no apparent benefit to continuing lamivudine therapy. Lamivudine R mutants remain sensitive to ADV with inhibition constants by 1.3 fold, 2.2 fold or decreasing by 0.8 fold. OLD TERMINOLOGY YMDD motif = M552I (methionine to isoleucine at codon 552) or M552V (methionine to isoleucine at codon 552) at conserved C subdomain (YMDD motif) of the HBV DNA Polymerase M552V is almost always seen with an additional mutation L528M (le