聚乙二醇化干扰素α联合阿德福韦对中国慢性乙型肝炎患者肾功能的联合影响
Combined effect of pegylated interferon α with adefovir on renal function in Chinese patients with chronic hepatitis B.
作者信息
Su Qian, Liu Yanyan, Li Jiabin
机构信息
Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University Department of Infectious Diseases, Chaohu Affiliated Hospital of Anhui Medical University, Hefei, China.
出版信息
Medicine (Baltimore). 2018 Aug;97(34):e12089. doi: 10.1097/MD.0000000000012089.
BACKGROUND
Long-term safety of treatment with hepatitis B virus (HBV) polymerase inhibitors is a concern. Adefovir dipivoxil (ADV) and/or interferon alfa (IFN-α) therapies have previously been associated with impairment of renal function. Limited data are available on the safety of combination therapy with nucleos (t)ide analogues (NAs) and IFN-α. The aim of this analysis was to assess the renal function during combined therapy with pegylated interferon α-2b (PEG-IFN-α-2b) and ADV versus PEG-IFN-α-2b alone in patients with chronic hepatitis B (CHB).
METHODS
We performed a multicenter, prospective, open-label, randomized-controlled trial of renal function data to investigate the efficacy of 48 weeks of therapy with PEG-IFN-α-2b and ADV versus PEG-IFN-α-2b alone in 102 patients with CHB in Anhui, China. Glomerular filtration rates (GFRs) were calculated by Cockcroft-Gault (CG), abbreviated Modification of Diet in Renal Disease (MDRD) study, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and were tested by repeated-measures 1-way analysis of variance within groups. A linear mixed effects model for repeated measures was also used to evaluate the association between baseline information and estimated glomerular filtration rate (eGFR) changes overtime in all enrolled patients. The model considered the baseline age, sex, HBV DNA, aminotransferase, treatment group, time, and group-by-time interaction as fixed effects and incorporated random effects for individual subjects.
RESULTS
After 48 weeks of therapy and further 24 weeks of follow-up, the eGFR decreased both in patients given PEG-IFN-α-2b single therapy and combined therapy. Age, HBV DNA, and combined therapy were significant negative predictive factors for eGFR changes.
CONCLUSION
The incidence of renal adverse events in both groups was low, and the combination therapy may have delayed, but reversible renal impairment.
背景
乙型肝炎病毒（HBV）聚合酶抑制剂治疗的长期安全性令人关注。阿德福韦酯（ADV）和/或干扰素α（IFN-α）治疗先前已与肾功能损害相关。关于核苷（酸）类似物（NAs）与IFN-α联合治疗安全性的数据有限。本分析的目的是评估聚乙二醇干扰素α-2b（PEG-IFN-α-2b）与ADV联合治疗与单独使用PEG-IFN-α-2b治疗慢性乙型肝炎（CHB）患者期间的肾功能。
方法
我们在中国安徽对102例CHB患者进行了一项多中心、前瞻性、开放标签、随机对照试验，以研究48周PEG-IFN-α-2b与ADV联合治疗与单独使用PEG-IFN-α-2b治疗的肾功能数据疗效。采用Cockcroft-Gault（CG）公式、简化的肾脏病饮食改良（MDRD）研究公式和慢性肾脏病流行病学协作组（CKD-EPI）公式计算肾小球滤过率（GFR），并在组内采用重复测量单因素方差分析进行检验。还使用重复测量的线性混合效应模型评估所有入组患者的基线信息与估计肾小球滤过率（eGFR）随时间变化之间的关联。该模型将基线年龄、性别、HBV DNA、转氨酶、治疗组、时间以及组间时间交互作用视为固定效应，并纳入个体受试者的随机效应。
结果
治疗48周并进一步随访24周后，接受PEG-IFN-α-2b单药治疗和联合治疗的患者eGFR均下降。年龄、HBV DNA和联合治疗是eGFR变化的显著负性预测因素。
结论
两组肾不良事件发生率均较低，联合治疗可能导致延迟但可逆的肾功能损害。
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