阿德福韦酯致范可尼综合征

Fanconi＇s syndrome induced by adefovir dipivoxil

1例50岁女性乙型肝炎肝硬化患者于8年前开始口服拉米夫定（100 mg/d）治疗.用药1年后出现拉米夫定耐药,加用阿德福韦酯10 mg/d.联合抗病毒治疗约6年后,患者出现下肢无力且症状逐渐加重,1年内相继出现右侧季肋区疼痛伴翻身困难、下肢活动受限和左侧季肋区疼痛.实验室检查示血磷0.55 mmol/L,血钙2.13 mmol/L,血尿酸98 μmol/L,考虑为范可尼综合征（FS）,停用阿德福韦酯和拉米夫定,换用替诺福韦酯（300 mg/隔日）.1个月后复查,患者血磷0.65 mmol/L,血钙2.25 mmol/L,血尿酸109 μmol/L;尿 pH 6.00,24 h尿钾69 mmol/L、钠384 mmol/L、氯350 mmol/L;骨密度检查示骨质疏松.明确阿德福韦酯相关FS的诊断,加用骨化三醇（0.25 μg/d）治疗.3个月后,患者双下肢无力症状明显好转,停用替诺福韦酯改用恩替卡韦（0.5 mg/d）治疗.停用阿德福韦酯半年后患者双下肢无力消失,两季肋区疼痛明显减轻,可耐受中等体力活动.血磷、钙、尿酸水平均恢复正常,尿电解质排出量明显减少.

A 50-year-old female patient with hepatitis B cirrhosis received oral lamivudine（100 mg/d） 8 years ago. Lamivudine resistance appeared one year after the administration. Then adefovir dipivoxil 10 mg/d was added. About 6 years after the combined antiviral treatments,weakness of lower limbs appeared and gradually worsened. At following one year,the patient successively presented with right hypochondrium pain accompanied by difficulty in turning over,limited movement of the lower extremities, and left hypochondrium pain. Laboratory tests showed serum phosphorus 0.55 mmol/L,serum calcium 2.13 mmol/L,and serum uric acid 98 mol/L. Fanconi syndrome（FS）was considered. Adefovir dipivoxil and lamivudine were discontinued and changed to tenofovir disoproxil（300 mg every other day）. After one month of treatment,laboratory tests showed serum phosphorus 0.65 mmol/L,serum calcium 2.25 mmol/L, serum uric acid 109 mol/L,urine pH 6.00,24 hours urine potassium 69 mmol/L,urine sodium 384 mmol/L, and urine chlorine 350 mmol/L. Bone mineral density examination showed osteoporosis. Adefovir dipivoxil-related FS was diagnosed and calcitriol（0.25 g/d）was added. Three months later,weakness of bilateral lower extremities was improved markedly. Tenofovir disoproxil was discontinued and changed to entecavir （0.5 mg/d）. Six months after discontinuation of adefovir dipivoxil,weakness of bilateral lower extremities subsided,right hypochondrium pain alleviated,and moderate physical activity could be tolerated,serum phosphorus,calcium,and uric acid levels returned to normal,and urine electrolyte output was obviously reduced.