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1 Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
2 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
3 State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
4 Department of Statistics, The Chinese University of Hong Kong, Hong Kong
5 Big Data Decision Analytics Research Centre, The Chinese University of Hong Kong, Hong Kong
*Corresponding Author: Henry LY Chan, MD Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong. Telephone: 852-2632-3942, Fax: 852-2637-3852, Email: [email protected]
Widespread and long-term use of oral nucleos(t)ide analogues (NAs) to treat chronic hepatitis B (CHB) brings about the safety data in real-life setting. We aimed to determine the risks of renal and bone side effects in patients receiving/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 (ICD-9-CM) 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. 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 [HR] ranged from 0.79-1.31; P=0.225-0.887). Exposure to nucleotide analogues, compared with nucleoside analogues, 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). Conclusions: NA treatment does not increase the risk of renal and bone events in general. Nucleotide analogues may increase the risk of hip fracture, but the overall event rate is low. This article is protected by copyright. All rights reserved.
摘要
广泛和长期使用口服核苷(酸)类似物(NAS)治疗慢性乙型肝炎(CHB)形成了现实生活中的安全数据。我们旨在确定那些正在或是已经接受了NAs来治疗CHB的病人在肾脏和骨骼方面产生副作用的风险。通过使用来自医院管理局(香港医疗服务的主要提供者)的数据库而进行的一项全港范围内的队列研究(百度百科:队列研究是将人群按是否暴露于某可疑因素及其暴露程度分为不同的亚组,追踪其各自的结局,比较不同亚组之间频率的差异,从而判定暴露因子与结局之间有无因果关联及关联大小的一种观察性研究方法。)我们按照国际疾病分类第9版,临床修订(ICD-9-CM)的诊断代码,认定2000和2012年的主要事件是肾脏(伴随而来的肾衰竭和肾替代疗法【RRT】)和骨事件(伴随而来的髋部,脊椎和所有骨折)。一项为期3年的里程碑式的分析被用于评估有与没有使用NA治疗的患者主要结果的相对风险。53,500名慢性乙肝患者(46454未治疗过和7046已治疗)并且近3年未出现过什么并发症,被纳入了本项分析。在平均4.9年的随访中,未治疗过的样本中,发生慢性肾功能衰竭,RRT,全部骨折,髋部骨折和脊椎骨折的概率分别为0.6%,0.2%,0.7%,0.1%,0.1%,已治疗的样本的概率为1.4%,0.7%,1.3%,0.2%,0.2%。经过倾向评分权重后发现,NA治疗并没有增加任何并发症的风险(风险比[HR]范围从0.79-1.31不等; P = 0.225-0.887)。