| Long-term Treatment with Adefovir Dipivoxil in Pre- and Post-Transplant Patients with Lamivudine-resistant HBV Results in Significant Improvement in Survival and Laboratory Functions?/font> Adefovir dipivoxil/ ADV (Hepsera) has potent in vivo and in vitro activity against wild-type and lamivudine-resistant (LAM-R) HBV. In pre- and post-orthotopic liver transplantation (pre- and post-OLT ) patients (pts) with LAM-R HBV, 48 weeks (wks) of ADV resulted in serum HBV DNA reductions of 4.1 and 4.3 log10 c/mL and ALT normalization in 68% and 79% of pts, respectively. No ADV resistance was seen in the first 48 weeks.
The objective of this study was to evaluate long-term safety, efficacy and resistance of ADV 10 mg in pre- and post-OLT pts with LAM-R HBV. 241 post-OLT (A) and 226 pre-OLT, decompensated liver disease (B) pts failing LAM were enrolled. ADV dose was adjusted for renal impairment (CLcr < 50 mL/min).
Results
Baseline (BL): median HBV DNA 8.2 and 7.4 log10 c/mL, and median ALT 2.0 and 1.8 x ULN in A and B, respectively; 83% (A) and 88% (B) male; median age 53 (A) and 52 (B) years; 78 % (A) and 70% (B) Caucasian. Median ADV duration 99 wks (max: 203 wks) in A and 52 wks (max: 153 wks) in B. 4 (2%) pts had re-OLT (A); 61 (27%) underwent OLT (B). HBV DNA reductions in the first 48 wks were maintained and/or improved throughout 144 wks.
Increasing proportions of pts normalized ALT over time. Based upon assessable Child-Pugh-Turcotte (CPT) scores, 95% (A) and 100% (B) had a stable or improved CPT at wk 96. Survival by wk 96 was 88% (A) and 78% (B) (Kaplan-Meier estimates).
Resistance up to 144 wks was seen in 2 (1.8%) pts between wks 48 and 96. Both pts had discontinued LAM prior to emergence of resistance. Addition of LAM to ADV resulted in re-suppression of HBV DNA.
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* 68% (A) and 57% (B) withdrew due to study closure with commercial availability
A low rate of related serious adverse events (AEs) were reported (6% A, 6% B), AEs leading to drug discontinuation (11% A, 15% B) were infrequent.
A total of 67 deaths were reported (27 A, 40 B); 22% and 38% of these occurred within 30 days of starting ADV. 15 pts died prior to initiating ADV. Confirmed changes in serum creatinine ≥ 0.5 mg/dL above BL by 144 wks were observed in 21% pts; the majority had renal dysfunction and/or multiple risk factors for renal dysfunction at BL. Only 2% of pts discontinued ADV for renal adverse events.
Conclusion
In conclusion, the authors write, 揂DV treatment over 144 wks resulted in significant reductions in serum HBV DNA, ALT normalization and other liver functions. The survival experience in the patients, pre- and post-OLT, together with the improvement in HBV DNA and other efficacy parameters is evidence of a clinically meaningful benefit. Long-term treatment was not associated with treatment limiting toxicity.?/span>
12/06/04 Reference
E Schiff and others.LONG-TERM SAFETY AND EFFICACY OF ADEFOVIR DIPIVOXIL (ADV) IN THE TREATMENT OF CHRONIC HEPATITIS B IN PATIENTS PRE-AND POST-LIVER TRANSPLANTATION (OLT) WITH LAMIVUDINE-RESISTANT (LAM-R) HEPATITIS B VIRUS (HBV). 55th AASLD. October 29-November 2, 2004. Boston, MA.
[此贴子已经被作者于2004-12-6 22:25:06编辑过] | 
发表于 2004-12-7 12:23
