Great news on ADV: 5% lost HbsAg over 5 year-->多多的老公转移

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

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