阿德福韦酯治疗中国慢性乙型肝炎患者二年的肾脏安全性分析

Renal safety of adefovir dipivoxil for two-year treatment in Chinese patients with chronic hepatitis B

目的 回顾性分析阿德福韦酯（ADV）治疗中国慢性乙型肝炎（CHB）患者2年的肾脏安全性.方法 本研究1 013例CHB患者均为中国ADV四期多中心临床研究（ADF30001和ADF106632）入选者.所有患者均口服ADV（10 mg/d）治疗,分析治疗104周内不同时间点的血磷和血肌酐变化.肾功能损害定义为连续2次检测血肌酐比基线升高≥44.2 μmol/L或血磷水平下降至＜0.4845 mmol/L.采用配对t检验对不同时间点的血磷、血肌酐与基线水平进行比较.结果 治疗28,52,80和104周时,患者血肌酐的中位值分别为74.963,76.996,76.820和77.969 μmol/L,与基线比较差异无统计学意义（t=0.91,0.23,0.59和0.97,P＞0.05）.无一例患者血肌酐升高≥44.2 μmol/L.治疗28,80和104周时,患者血磷的中位值分别为1.098,1.088和1.048 mmol/L,与基线比较差异具有统计学意义（t=2.34,3.06和4.94,P＜0.05或＜0.01）.至治疗104周累计血磷异常下降发生率为0.8％ （8/104）.无一例患者发生血磷下降至＜0.4845 mmol/L.结论 ADV治疗2年未见明显的肾功能损害,中国CHB患者对ADV治疗的耐受性良好.

Objective To assess the renal safety of adefovir dipivoxil （ADV） in Chinese patients with chronic hepatitis B （CHB）.Methods A retrospective study was performed on 1 013 CHB patients from Chinese ADV multicenter clinical trials （ADF30001 and ADF106632）.All patients were administrated with ADV 10 mg daily.The serum creatinine and phosphorus levels were measured in different time pointsduring 104-week treatment.Nephrotoxicity was defined as an increase ≥44.2 μ mol/L from baseline in serum creatinine or a serum phosphorus value of ＜ 0.4845 mmol/L on two consecutive occasions.Paired t test was used to analyze serum creatinine and phosphorous data before treatment and at different time points during treatment.Results At week 28,week 52,week 80 and week 104,the median levels of serum creatinine were 74.963,76.996,76.820 and 77.969 μmol/L,respectively,and there were no significant differences from baseline （t =0.91,0.23,0.59 and 0.97,P ＞ 0.05）.No patient experienced a ≥ 44.2 μmol/L increase from baseline.For serum phosphorus,the median levels at week 28,week 80 and week 104 were 1.098,1.088 and 1.048 mmol/L,and there were significant decreases from baseline （t =2.34,3.06 and 4.94,P ＜0.05 or ＜ 0.01）.The cumulative incidence of serum phosphorus abnormality was 0.8％ （8/104）.There were no confirmed serum phosphorous decreases to ＜ 0.4845 mmol/L.Conclusion Two years treatment with ADV （10 mg/d） does not result in marked nephrotoxicity,indicating that ADV 10 mg daily is well tolerated by Chinese patients.