39例阿德福韦酯相关肾性低磷血症及骨软化症临床分析和初步转归  

Clinical features and individualized treatment of 39 cases of adefovir dipivoxil-induced renal hypophosphatemia and osteomalacia

作　　者：曲云东[1] 叶茜[1] 王磊[1] 刘峰[1] 钱钰[1] 王子瑜[1] 张立新[1] 

机构地区：[1]山东大学第二医院感染/肝病科,济南250033

出　　处：《中华传染病杂志》2015年第11期678-681,共4页Chinese Journal of Infectious Diseases

基　　金：艾滋病和病毒性肝炎等重大传染病防治和“十二五”国家科技重大专项“山东省乙型病毒性肝炎防治综合示范区规模化现场流行病学和干预研究”项目（2013ZX10004902）;山东省医药卫生科技发展计划项目（2014WS0424）

摘　　要：目的研究阿德福韦酯（ADV）治疗CHB和乙型肝炎肝硬化所致肾性低磷血症及骨软化症的临床特点，探讨早期诊断和干预措施。方法连续收集ADV治疗CHB或乙型肝炎肝硬化发生肾性低磷血症患者，总结临床特点，随访转归。结果共收集39例患者，男26例，女13例，平均年龄为54（27～71）岁，其中乙型肝炎肝硬化19例；平均ADV服用时间69（18～116）个月，31例用药36～96个月；平均血磷0．68（0．42～0．79）mmol／L，低磷骨软化症26例；14例发生骨痛，19例碱性磷酸酶升高；3例血肌酐升高，24例肾小球滤过率下降。干预后，血磷于2．0（0．5～6．0）个月复常；骨痛0．8（0．2～1.0）个月开始缓解，1．5（0．5～5．0）个月消失；肝功能、肾功能及肾损伤指标逐渐恢复；骨密度改善缓慢。结论长期应用ADV的部分CHB和乙型肝炎肝硬化患者可出现ADV相关肾性低磷血症及骨软化症，且具有可逆性。应用ADV的患者应定期监测血磷、肾功能和肾损伤等指标。确诊后应停用或减量ADV，换替比夫定或恩替卡韦及对症治疗，并密切监测血磷和HBVDNA等指标。Objective To investigate the clinical features, early diagnosis and individualized treatment of renal hypophosphatemia and osteomalacia induced by adefovir dipivoxil （ADV） in patients with chronic hepatitis B （CHB）. Methods Thirty-nine CHB or hepatitis B virus （HBV）-related cirrhosis patients of renal hypophosphatemia and osteomalacia induced by ADV were consecutively collected. The clinical features were analyzed and treatment outcome was followed up. Results The mean age of the 39 patients was 54 （27--71） years old. There were 26 male and 13 female patients, and 19 patients with cirrhosis. The mean ADV treatment duration was 69 （range 18- 116） months, and 31 patients were treated for 36--96 months. The mean serum phosphate was 0. 68 （0.42-0.79） mmol/L. Twenty-six cases developed renal hypophosphatemic osteomaolacia, of which 14 had bone pain and 19 had abnormally elevated alkaline phosphatase （ALP）. Three patients had increased serum creatinine and 24 patients had decreased estimated glomerular filtration rate （eGFR）. After individualized treatment, patients gained normal serum phosphate in mean of 2.0 （range 0.5-6.0） months, and had bone pain remission in the mean of 0.8 （range 0.2 - 1.0） month and bone pain disappeared in the mean of 1.5 （range 0.5 - 5.0） months. Function indices of liver and kidney were improved gradually, and the bone mineral density examination improved slowly. Conclusions CHB and HBV-related cirrhosis patients treated with long- term ADV could develop renal hypophosphatemia and hypophosphatemic osteomalacia, which is partially reversible. Monitoring serum phosphate, creatinine and cystatin C is necessary during long-term ADVtherapy. After confirmed diagnosis, withdrawal or dosage reduction of ADV, and switch to telbivudine or entecavir should be considered. Meanwhile, serum phosphate and HBV DNA level should be monitored.

关 键 词：阿德福韦酯 低磷血症 骨软化症 肝炎 乙型 慢性 

分 类 号：R512.62[医药卫生—内科学]