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本帖最后由 齐欢畅2 于 2010-11-3 23:31 编辑
三月份亚太肝病学会发表的文章
Preliminary Evidence of Rapid HBsAg Seroconversion in Patients with Chronic Hepatitis B (CHB) Treated with a DNA-based Amphipathic Polymer.
Mamun Al-Mahtab, Michel Bazinet, Andrew Vaillant
Background: REP9AC is a DNA-based amphipathic polymer whose antiviral activity is linked to targeting viral glycoproteins important for viral entry and/ or release. The preclinical evaluation of 28 days of REP 9AC therapy in ducks persistently infected with DHBV demonstrated rapid clearance of DHBV DNA, DHBsAg and rapid appearance of anti-DHBs antibodies in 55% of ducks whose blood had no detectable evidence of DHBV infection 16 weeks after cessation of REP 9AC therapy. The ability of REP 9AC to treat human patients with CHB is currently being evaluated in a proof of concept trial.
Methods: Patients with CHB were subjected to REP9AC therapy administered by slow continuous infusion. Safety and virologic response (HBV DNA, HBsAg, anti-HBs) were assessed weekly, either at the trial site or by confirmatory testing (HBsAg, HBeAg, anti-HBs, anti-HBe) of frozen serum samples at a separate location using the ArchitectTM testing platform.
Results: Interim data has shown that all patients treated to date have cleared HBsAg and developed protective immunity. Clearance of HBsAg and development of protective levels of anti-HBs occurred as early as 7 days following initiation of treatment at higher doses. At the time of abstract submission, one patient has already exhibited clear signs of a sustained virologic response (HBV DNA -, HBsAg -, HBeAg -, anti-HBs +, anti-HBe +) for 8 continuous weeks off treatment after receiving only 23 weeks of treatment with REP9AC.
Conclusions: These results demonstrate that amphipathic polymers are effective in rapidly reducing HBsAg levels in CHB patients which allows patients to seroconvert. The rapid appearance of anti-HBs and anti-HBe antibodies in these patients, the best predictors of SVR in patients with CHB, suggest that amphipathic polymers could become an important new tool in the treatment of CHB.
这次美国肝病学年会发表的文章：
482. REP 9AC: A Potent HBsAg Release Inhibitor That Can Rapidly Restore Immunocompetence in Patients with Chronic Hepatitis B. M. A. Mahtab; M. Bazinet; A. Vaillant
Background: Many groups have suggested that HBsAg may play a role in suppressing the immune system and may allow the infection to be chronically maintained in the liver. REP 9AC is a DNA-based amphipathic polymer which has been shown to potently inhibit the release of HBsAg from infected hepatocytes. In preclinical studies in DHBV infected ducks, DHBsAg seroclearance was observed in all ducks after only two weeks of treatment. Four weeks of REP 9AC therapy resulted in 55% of ducks achieving a SVR 16 weeks after cessation of treatment. The ability of REP 9AC to treat human patients with chronic hepatitis B (CHB) is currently being evaluated in a proof of concept clinical trial.
Methods: All patients were HBeAg+, HBsAg+ with pre-treatment HBV DNA titers between 106 and 1012 copies/ml. Additionally, all patients were shown to have significant liver fibrosis as assessed by pre-treatment liver biopsy. Patients with CHB were subjected to parenteral REP 9AC therapy. Safety and virologic response (HBV DNA, HBsAg, anti-HBs) were assessed weekly during treatment, either at the trial site or by confirmatory testing (HBsAg, HBeAg, anti-HBs, anti-HBe) of frozen serum samples at a separate location using the Architect™ testing platform.
Results: Interim data shows that 5 out of 6 patients treated to date have cleared serum HBsAg and anti-HBsAg antibodies have been observed in all patients. Clearance of HBsAg and development of anti-HBs have been observed as early as 7 days and no later than 15 weeks following initiation of treatment at higher doses. At the time of abstract submission, 3 patients have achieved a 3 to 7 log reduction in their HBV DNA titers from pre-treatment levels after 7-13 weeks of treatment. Additionally, two other patients have achieved a complete control of their infection after 23 or 24 weeks of treatment (HBV DNA -, HBsAg -, HBeAg -, anti-HBs +, anti-HBe +) and are being followed off treatment. One of these patients is currently maintaining control over his infection 6 months after stopping treatment.
Conclusions: These results demonstrate that REP 9AC can rapidly and effectively clear HBsAg from the serum of infected patients. This rapid HBsAg seroclearance appears to allow the restoration of an effective immune response, as evidenced by substantial reductions in serum HBV DNA, seroconversion for HBsAg and HBeAg, and the achievement of a 6 month SVR in at least one patient to date. These results suggest that REP 9AC may become an important new tool in the treatment of chronic hepatitis B.
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楼主: 齐欢畅2
发表于 2010-10-26 21:45
