Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.
Hepatology. 2015 Sep;62(3):684-93. doi: 10.1002/hep.27894. Epub 2015 Jul 28.
Widespread and long-term use of oral nucleos(t)ide analogs (NAs) to treat chronic hepatitis B (CHB) brings about safety data in a real-life setting. We aimed to determine the risks of renal and bone side effects in patients receiving or who have received NAs as CHB treatment. A territory-wide cohort study using the database from Hospital Authority, the major provider of medical services in Hong Kong, was conducted. We identified CHB patients by International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes, diagnosed between 2000 and 2012. The primary events were renal (incident renal failure and renal replacement therapy [RRT]) and bone events (incident hip, vertebral, and all fractures). A 3-year landmark analysis was used to evaluate the relative risk of primary outcome in patients with or without NA treatment. A total of 53,500 CHB patients (46,454 untreated and 7,046 treated), who were event free for 3 years, were included in the analysis. At a median follow-up of 4.9 years, chronic renal failure, RRT, all fractures, hip fractures, and vertebral fractures occurred in 0.6%, 0.2%, 0.7%, 0.1%, and 0.1% of untreated subjects and 1.4%, 0.7%, 1.3%, 0.2%, and 0.2% of treated subjects. After propensity score weighting, NA therapy did not increase the risk of any of the events (hazard ratios [HRs] ranged from 0.79 to 1.31; P = 0.225-0.887). Exposure to nucleotide analogues, compared with nucleoside analogs, increased the risk of hip fracture (HR = 5.69; 95% confidence interval: 1.98-16.39; P = 0.001), but not other events (HR = 0.58-1.44; P = 0.202-0.823).
NA treatment does not increase the risk of renal and bone events in general. Nucleotide analogs may increase the risk of hip fracture, but the overall event rate is low.
确定接受或曾经接受核苷（酸）类似物（NAs）治疗慢性乙型肝炎（CHB）的患者发生肾脏和骨骼副作用的风险。
我们进行了一项全港范围的队列研究，使用香港主要医疗服务提供者医院管理局的数据库。我们通过国际疾病分类，第九修订版，临床修正诊断代码识别 CHB 患者，诊断时间为 2000 年至 2012 年。主要事件是肾脏（急性肾衰竭和肾脏替代治疗[RRT]）和骨骼事件（髋部、椎体和所有骨折）。使用 3 年时间窗来评估有或无 NA 治疗的患者主要结局的相对风险。
共纳入 53500 例 CHB 患者（46454 例未治疗和 7046 例治疗），这些患者在 3 年内无事件发生。中位随访时间为 4.9 年，未治疗组中慢性肾衰竭、RRT、所有骨折、髋部骨折和椎体骨折的发生率分别为 0.6%、0.2%、0.7%、0.1%和 0.1%，治疗组中分别为 1.4%、0.7%、1.3%、0.2%和 0.2%。在倾向评分加权后，NA 治疗并未增加任何事件的风险（风险比[HR]范围为 0.79 至 1.31；P=0.225-0.887）。与核苷类似物相比，核苷酸类似物的暴露增加了髋部骨折的风险（HR=5.69；95%置信区间：1.98-16.39；P=0.001），但不增加其他事件的风险（HR=0.58-1.44；P=0.202-0.823）。
一般来说，NA 治疗不会增加肾脏和骨骼事件的风险。核苷酸类似物可能会增加髋部骨折的风险，但总体事件发生率较低。
