Great news: 5% HbsAg seroconversion rate over 5 year ADV treatment-->多多的老

US-8888

Five-year Treatment with Adefovir Results in Regression of Liver Fibrosis in Patients with HBeAg-negative Chronic Hepatitis B

Adefovir dipivoxil/ ADV [Hepsera] has shown efficacy and safety in HBeAg-negative patients in a randomized, placebo-controlled trial over 96 weeks.

Patients on ADV in year 2 were offered 3 more years of open label ADV. Efficacy and safety were analyzed after 4 years (Y4, n=55) and 5 years (Y5, n=70) of ADV, among patients randomized to placebo or ADV for the initial 48 weeks and then ADV thereafter.

The histologic data presented herein represent the first 5-year prospective, systematic set of biopsy results published from a trial of an oral antiviral.

Assessments included HBV DNA (Roche Amplicor Monitor LLQ 1000 copies/mL) and ALT every 12 weeks; liver biopsies at baseline (BL), Y1, Y2 (optional), and end of study (either Y4 or Y5); and annual resistance surveillance if HBV DNA >LLQ. All analyses were of observed data except histology (ITT last observation carried forward for Y2).

Results

• Baseline (BL) characteristics (n=125) were: 82% male; 70% Caucasian; 27% Asian; median age 47 years; median serum HBV DNA 7.10 log10 copies/ml; median Ishak fibrosis score 2.0.
• Liver histology was available from 46 patients who received either 4 (n=22) or 5 (n=24) years of ADV treatment; Y2 biopsies were not performed in all patients.
• Necroinflammation showed improvement from the first year of therapy, and by ranked assessment over 80% of patients improved at Y4 or Y5 compared to BL.
• The proportion of patients with >=1 point decrease in Ishak fibrosis consistently increased over 5 continuous years of ADV treatment (8/24 [33%] at Y1, 11/24 [46%] at Y2, and 17/24 [71%] at Y5; p=0.005 Cochran-Armitage exact test).
• Among 12 patients with bridging fibrosis or cirrhosis at BL, 7 improved >=2 points after 4 or 5 years of treatment.
• Six patients (5%) had HBsAg loss, 5 with anti-HBs at the last available time point.
• The percentage of patients with HBV DNA <1000 copies/mL was 26/40 (65%) at Y4 and 37/55 (67%) at Y5, and ALT normalized in 21/30 (70%) and 38/55 (69%), respectively.
• The cumulative probability of ADV resistance (A181V and/or N236T mutations) was 0%, 3%, 11%, 18%, and 28% at weeks 48, 96, 144, 192, and 240, respectively.
• By year 5, 1 patient (<1%) had confirmed serum phosphorus <2.0 mg/dL and 4 patients (3%) had confirmed increase in serum creatinine >=0.5 mg/dL above BL.
• Serious adverse events not related to ADV were reported in 22 patients (18%).

Conclusions

Treatment with ADV 10 mg QD for 5 years produced significant and increasing improvement in hepatic fibrosis confirming that durable viral suppression impacts fibrosis over time. The 5-year treatment was generally well-tolerated and the onset of resistance delayed.

hbsab1

转学术讨论版

新的希望GG

Yeah, maybe a good news. But just hope oneday could recover to be as a non-HbsAg carrier.

zongyawei

巨大新闻： 带有带有HBeAg负值慢性的肝炎B Adefovir dipivoxil/ ADV [ Hepsera ]的患者中的肝脏纤维变性的衰退中的Adefovir结果的5%种HbsAg seroconversion率超过5年ADV treatmentFive-year治疗已在随机化中的HBeAg消极患者中显示功效和安全，为死者唱晚祷词控制的试验超过96个星期。

在ADV上的患者2年3更多年的敞开的标签ADV被提供。 功效和安全在4年( Y4，n=55 )和5年( Y5，n=70 )的ADV之后被分析，在患者中间此后有初始的48个星期随机化成为为死者唱晚祷词或者ADV和然后ADV。

histologic数据提出在这里代表头5年预期而系统的套用口头抗病毒的一种试验被出版的活组织检查结果。

评估每12星期包括HBV脱氧核糖核酸( Roche Amplicor监控LLQ 1000年拷贝与mL )和ALT； 在基线( BL )的肝脏活组织检查，Y1，Y2 (可选)，和研究( Y4或者Y5 )的末端； 同时，年度的抵抗监视如果HBV脱氧核糖核酸>LLQ。 所有分析具有除组织学( ITT最后的观察为了Y2推进)之外的观察的数据。

结果基线( BL )特色( n=125 )是： 男性的82%； 70%个高加索人； 27%个亚洲人； 中央的年龄47年； 中央的血清HBV脱氧核糖核酸7.10个log10拷贝/ ml； 中央的Ishak纤维变性获得2.0。
肝脏组织学由收到4 ( n=22 )的46名患者提供或者5 ( n=24 )年的ADV治疗； Y2活组织检查在所有患者中不是被执行。
Necroinflammation从第一年的疗法显示改进，和通过分成等级的评估患者中的超过80%个在Y4或者Y5与BL相比而改进。
带有>=1点的患者的比例在一致的Ishak纤维变性上减少增加的超过5种连续的多年的ADV治疗( 8/24 [ 33% ] Y1，11/24 [ 46% ] Y2，和17/24 [ 71% ] Y5； p=0.005 Cochran Armitage确切的测试)。
在带有在BL为纤维变性或者肝硬化架桥的12名患者中间，7在4或者5年的治疗之后改进>=2点。
六名患者( 5% )有在最后的可供使用时间HBsAg损失，5反HB点。
带有HBV脱氧核糖核酸< 1000年拷贝与mL Y4和37/55 ( 67% )在21/30 ( 70% )和38/55 ( 69% )是26/40 ( 65% ) Y5，和ALT分别地规格化，。的患者的百分比
ADV抵抗( A181V和/或者N236T变化)的累积的可能性是0%，3%，11%，18%，和28% 48，96，144，192若干星期，和240，分别地。
年5，1个患者( <1% )曾经确认血清磷< 2.0 mg / dL和4名患者( 3% )曾经确认在BL之上的血清creatinine >=0.5 mg / dL的增加。
并非与ADV有关的严肃的不利事件在22名患者( 18% )中被报告。
带有ADV 10 mg QD的结论治疗因为5年生产确认那耐用的病毒压制的肝的纤维变性的有意义的和增加的改进冲击在