2nd Academic Department of Internal Medicine, Hippokration Hospital of Athens, Athens, Greece.
Liver Int. 2011 Nov;31(10):1525-32. doi: 10.1111/j.1478-3231.2011.02616.x. Epub 2011 Aug 11.
BACKGROUND/AIMS: As there are concerns about potential nephrotoxicity of nucleotide analogues, we evaluated renal function parameters during long-term adefovir and lamivudine combination therapy.
Forty-six HBeAg-negative patients with lamivudine-resistance treated with adefovir and lamivudine for up to 90 months were included. Renal function was assessed by estimated creatinine clearance (eC(CR) ) and compared with a matched control group of untreated inactive hepatitis B virus carriers.
Serum HBV DNA became undetectable in 39 (85%) patients after a mean of 37 ± 21 months. Three (6.5%) patients developed virological breakthrough. Adefovir resistance was detected in two patients. At the end of follow up, there was a significant decrease in mean eC(CR) (95 ± 31-83 ± 30 ml/min, P = 0.003) in the treated patients with 16% presenting aeC(CR) decrease >30%. Similar changes in eC(CR) were observed in the control group (108 ± 28-96 ± 26 ml/min, P = 0.003). In multiple regression analysis, age and baseline eC(CR) were independent predictors of eC(CR) reduction.
Adefovir and lamivudine combination therapy is not an independent factor for significant renal dysfunction in HBeAg-negative patients with lamivudine-resistance. Baseline age and creatinine clearance are the only independent predictors of worsening renal function.
背景/目的：由于核苷酸类似物存在潜在肾毒性的担忧，我们评估了阿德福韦酯和拉米夫定联合治疗的长期过程中肾功能参数的变化。
共纳入 46 例对拉米夫定耐药的 HBeAg 阴性患者，这些患者接受阿德福韦酯和拉米夫定联合治疗，疗程最长达 90 个月。通过估算的肌酐清除率（eC（CR））评估肾功能，并与未经治疗的非活动性乙型肝炎病毒携带者的匹配对照组进行比较。
平均 37 ± 21 个月后，39 例（85%）患者的血清 HBV DNA 检测不到。3 例（6.5%）患者发生病毒学突破。两名患者检测到阿德福韦耐药。随访结束时，治疗组患者的平均 eC（CR）显著下降（95 ± 31-83 ± 30 ml/min，P = 0.003），其中 16%的患者 eC（CR）下降超过 30%。对照组患者也观察到 eC（CR）相似的变化（108 ± 28-96 ± 26 ml/min，P = 0.003）。多元回归分析显示，年龄和基线 eC（CR）是 eC（CR）下降的独立预测因素。
阿德福韦酯和拉米夫定联合治疗不是对拉米夫定耐药的 HBeAg 阴性患者发生显著肾功能障碍的独立因素。基线年龄和肌酐清除率是肾功能恶化的唯一独立预测因素。
