慢性HBV感染患者长期服用阿德福韦酯与肾性低磷血症的相关因素  

Hypophosphatemia during long-term adefovir dipivoxil therapy in patients with hepatitis B virus infection

作　　者：刘秋霞[1] 王磊[1] 刘峰[1] 曲云东[1] 叶茜[1] 钱钰[1] 张媛[2] 张立新[1] LIU Qiuxia WANG Lei LIU Feng QU Yundong YE Qian QIAN Yu ZHANG Yuan ZHANG Lixin(Department of Hepatology Center of Evidence-based Medicine, Second Hospital of Shandong University, Jinan 250033, Shandong, China)

机构地区：[1]山东大学第二医院肝病科,山东济南250033 [2]山东大学第二医院循证医学中心,山东济南250033

出　　处：《山东大学学报（医学版）》2017年第7期73-78,共6页Journal of Shandong University:Health Sciences

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：目的探讨慢性乙型肝炎病毒(HBV)感染患者中阿德福韦酯(ADV)相关肾性低磷血症的发生率及影响因素。方法回顾性分析自2005年6月至2015年6月在山东大学第二医院开始接受ADV或ADV联合拉米夫定(LAM)抗病毒治疗并随诊1年以上的慢性HBV感染患者的临床资料。评估血清磷酸盐水平、血清肌酐和估计肾小球滤过率(e GFR),采用Kaplan Meier方法计算低磷血症的累积发生率。结果 243例慢性HBV感染患者中,慢性乙型肝炎(慢乙肝)和乙型肝炎肝硬化(乙肝肝硬化)分别是171例和72例,服用ADV的中位数时间为66(12~120)个月,有24例患者发生低磷血症。在2~10年时慢乙肝和乙肝肝硬化的低磷血症累计发生率分别为:0.6%、0.6%、0.6%、3.2%、6.2%、11.2%、14.2%、14.2%、19.9%和1.5%、3.3%、7.9%、10.4%、13.7%、23.9%、32.3%、49.3%、49.3%(χ~2=6.685,P=0.010)。Cox多因素分析提示,ADV联合LAM(HR=2.661,P=0.010)、乙肝肝硬化(HR=2.886,P=0.020)是低磷血症发生的独立危险因素。结论慢性HBV感染患者长期服用ADV可引起低磷血症。LAM联合ADV以及肝硬化患者更易发生。Objective To assess the cumulative incidence of hypophosphatemia caused by long-term treatment with ade- fovir dipivoxil （ADV） in patients with hepatitis B virus （HBV） infection and to explore the risk factors. Methods The patients who received ADV monotherapy or ADV plus lamivudine （LAM） for more than 1 year were recruited. Serum phosphate level, serum creatinine and estimated glomerular filtration rate （eGFR） were evaluated. Cumulative incidences of hypophosphatemia were calculated with Kaplan-Meier method. Results Of the 243 cases involved, 171 were chronic hepatitis B （CHB） and 72 were liver cirrhosis （LC）. During a median treatment duration of 66 （12- 120） months, 24 patients developed hypophosphatemia. The cumulative incidences of hypophosphatemia for CHB and LC cases during 2-10 years were 0.6%, 0.6%, 0.6%, 3.2%, 6.2%, 11.2%, 14.2%, 14.2%, 19.9%, and 1.5%, 3.3%, 7.9%, 10.4%, 13.7%, 23.9%, 32.3%, 49.3% and 49.3%, respectively （x^2 =6.685, P= 0. 010）. Multivariate analysis identified LC （HR =2. 886, P =0.020） and ADV plus LAM （HR =2. 661, P =0. 010） as independent predictors of hypophosphatemia. Conclusion Long-term treatment of hepatitis B with ADV or ADV plus LAM can potentially cause hypophosphatemia. LC patients treated with ADV plus LAM are more likely to develop hypophosphatemia.

关 键 词：慢性乙型肝炎 阿德福韦酯 低磷血症 

分 类 号：R512.6[医药卫生—内科学]