阿地福韦对拉米耐药移植患者临床效果显著（2005.4.20 EASL）

zasxz

Adefovir Dipivoxil Provides Significant Clinical Benefit and Prevents Transplantation in HBV Patients with Lamivudine Resistance Wait-listed for Organ Transplantation

Adefovir dipivoxil/ADV (Hepsera) has potent activity against wild-type and lamivudine-resistant (LAM-R) hepatitis B Virus (HBV). In patients with LAM-R HBV, pre and post- orthotopic liver transplantation (OLT), ADV significantly reduces serum HBV DNA, normalizes ALT and improves liver function.

226 patients waitlisted for OLT and failing LAM were enrolled in this international study.

Results

Baseline characteristics were 88% male, 70% Caucasian, median age 52 years. Disease characteristics (median) were serum HBV DNA, 7.4 log10 copies/mL; ALT 1.8 x ULN, CPT score 7.0.

· Thirty-two patients died awaiting OLT, 47% of them within 30 days of starting ADV and 8 deaths occurred post-OLT.

· Patients failing lamivudine/ LAM (Epivir-HBV) had advanced liver disease and a high mortality risk. Cumulative survival was 77% up to 96 weeks (Kaplan-Meier estimates).

· In the pre-OLT cohort, clinical improvement was associated with mean reductions in MELD score of 3.8 and 5.1 by weeks 48 and 96.

· The majority of patients continued LAM after ADV initiation. ADV resistance (N236T) was identified in 3 patients. All 3 discontinued LAM following HBV DNA suppression with ADV.

· Resistance was not seen in patients on ADV added to ongoing LAM.

· Serum creatinine elevations (0.5mg/dL or greater above baseline) occurred more frequently in patients with on study OLT (47% compared to 6% waitlisted).

· Only 2% percent of patients discontinued ADV for renal adverse events, All patients with renal changes had risk factors for renal dysfunction at baseline.

Conclusion

The authors conclude, “ADV 10 mg resulted in significant improvements in clinical and laboratory parameters in patients with advanced liver disease, failing LAM, waitlisted for OLT. Downgrading or removal from the transplant list was possible in many patients.”

“Long-term treatment was not associated with treatment-limiting toxicity. LAM-resistance was associated with a high rate of early mortality. ADV initiation should not be delayed in this setting .”

zasxz

04/18/05

Reference E Schiff and others. ADEFOVIR DIPIVOXIL (ADV) PROVIDES SIGNIFICANT CLINICAL BENEFIT, REDUCES MELD SCORE AND PREVENTS TRANSPLANTATION IN CHRONIC HEPATITIS B PATIENTS WAIT-LISTED FOR LIVER TRANSPLANTATION(OLT) WITH LAMIVUDINE-RESISTANCE (LAM-R). Abstract 7 . 40th EASL. April 13-17, 2005. Paris, France.