评论性文章：在HBV-monoinfected患者核苷和核苷酸类似物的长期

StephenW

Review article: long-term safety of nucleoside and nucleotide analogues in HBV-monoinfected patients

    P. Lampertico1,*, H. L. Y. Chan2, H. L. A. Janssen3, S. I. Strasser4, R. Schindler5 andT. Berg6

Version of Record online: 19 MAY 2016

DOI: 10.1111/apt.13659

© 2016 John Wiley & Sons Ltd

Issue
Cover image for Vol. 43 Issue 12
Alimentary Pharmacology & Therapeutics

Early View (Online Version of Record published before inclusion in an issue)
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Summary
Background

Nucleos(t)ide analogues (NUCs) for chronic hepatitis B treatment achieve high rates of viral suppression and are generally well tolerated. Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are the currently preferred first-line agents. The safety of these agents in clinical practice is particularly relevant since long-term treatment is usually required.
Aim

To summarise and critically discuss recent real-world evidence on the safety of treatment with ETV or TDF in hepatitis B virus (HBV)-monoinfected patients.
Methods

PubMed and conference proceedings up to 15th June 2015 were searched using the terms ((((Hepatitis_B) OR HBV) AND ((tenofovir) OR entecavir)) AND (((lactic_acidosis) OR bone) OR renal)).
Results

In selected populations included in registration studies, both ETV and TDF were well tolerated with no clinically significant renal toxicity or lactic acidosis. Growing ‘real-world’ clinical experience with these agents includes some reports of ETV-associated lactic acidosis and TDF-associated renal impairment; however, evidence from cohort studies appears to be conflicting. In the case of ETV-related lactic acidosis, a small number of cases have been reported, all in patients with decompensated cirrhosis. The degree of association between TDF treatment and changes in markers of renal function varies between studies: discrepancies may result from the use of different definitions and cut-offs for reporting renal toxicities, and differences in patient populations.
Conclusions

Pre-treatment and on-treatment monitoring of eGFR and phosphorus, with prompt appropriate dose adjustment or treatment switch can minimise the impact of NUC renal toxicity. Standardisation of measures of renal impairment and identification of early molecular markers remain an unmet need.

StephenW

评论性文章：在HBV-monoinfected患者核苷和核苷酸类似物的长期安全性

    P. Lampertico1，*，H. L. Y. CHAN2，H. L. A. Janssen3，S.一Strasser4，R. Schindler5和T。 Berg6

2016年5月19日：记录在线版本

DOI：10.1111 / apt.13659

2016年©约翰·威利父子有限公司

问题
封面图片的卷。 43第12期
消化系统药理学和治疗

早期的视图（记录的网上版本包括前一个问题出版）
文章中4的比分altmetric

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概要
背景

核苷（酸）类似物（NUCs）用于慢性乙型肝炎治疗达到病毒抑制率较高，一般耐受性良好。恩替卡韦（ETV）和富马酸替诺福韦酯（TDF）是目前优选的一线药物。在临床实践中，这些药物的安全性是特别相关的，因为通常需要长期治疗。
目标

为了总结和批判性讨论治疗与ETV或TDF在乙型肝炎病毒（HBV）-monoinfected病人的安全最近真实世界的证据。
方法

考研和会议记录达2015年6月15日进行了使用条款（（（（Hepatitis_​​B）或HBV）AND（（替诺福韦）或恩替卡韦））AND（（（lactic_acidosis）或骨）或肾））搜索。
结果

在纳入注册研究选择的人群，ETV和TDF两人都很好，没有临床显著肾毒性或乳酸性酸中毒的耐受性。不断增长的“真实世界”这些药物的临床经验，包括ETV相关的乳酸性酸中毒和TDF相关的肾功能损害的一些报告;然而，从队列研究的证据似乎是相互矛盾的。在ETV相关乳酸性酸中毒的情况下，病例少数已报道，所有患者的失代偿性肝硬化。 TDF治疗和变化之间的关联性的肾功能的标志物的程度的研究之间变化：可能会导致从使用不同的定义和切割取舍报告肾毒性，和在患者群体差异的差异。
结论

前处理和治疗监测的eGFR和磷，以提示适当调整剂量或治疗开关可以最小NUC肾毒性的影响。肾损害和早期分子标记鉴定的标准化措施仍然是一个尚未满足的需求。

StephenW

We suggest that for standard monitoring of patients receiving TDF in clinical practice, in agreement with AASLD guidelines, serial measures of serum creatinine (eGFR) and serum phosphate should be made at baseline and every 3–6 months (Table 5). In a clinical research setting, signs of tubular damage can be monitored using spot urine samples taken every 3–6 months to measure protein, albumin and creatinine and calculate urinary albumin–creatinine or protein–creatinine ratios.[79] As a result of proximal tubular injury, TDF may cause urinary leakage of proteins that are not albumin but of lower molecular weight.[28] In this context, it is important to mention that normal urine dipstick tests predominantly detect albumin; thus dipsticks are not appropriate to monitor NUC nephrotoxicity. Careful monitoring of renal function and proactive dose adjustment of TDF minimises the risk of renal toxicity. Where TDF-related renal impairment arises, in patients who have not previously received LVD a switch to ETV may restore renal function while maintaining viral suppression. For patients who have previous LVD experience TDF dose reduction should be tried first. If a switch to ETV is needed it should be accompanied by close viral load monitoring and careful, gradual reintroduction of TDF should be considered once renal symptoms have abated. However, in the case of Fanconi's syndrome treatment should be switched rapidly regardless of prior LVD history. In this case, the resulting improvement in renal function should be quickly apparent.
我们建议，对于接收的TDF在临床实践中，在与AASLD指南协议患者标准的监测，血清肌酐（EGFR）和血清磷酸盐的串行措施应在基线和每3-6个月（表5）进行。在临床研究的设置，肾小管损伤的迹象可以使用取点尿样品每3-6个月来测量蛋白质，白蛋白和肌酸酐，计算尿白蛋白肌酐或蛋白质 - 肌酸酐比率进行监测。[79]作为近端的结果肾小管损伤，TDF可能导致不白蛋白但较低分子量的蛋白质的漏尿[28]在这种情况下，它提及正常尿试纸测试主要检测白蛋白是重要的。;因此试纸是不恰当的监测NUC肾毒性。肾功能和TDF的主动调整剂量仔细监测减少肾毒性的危险。其中，TDF相关肾损害发生时，在谁没有先前接收的LVD患者开关ETV可能，同时保持病毒抑制恢复肾功能。对于谁拥有以前的经验，LVD TDF减少剂量的患者，应首先尝试。如果需要切换到ETV应该很近病毒载量监测和TDF的细心，逐步放归伴随肾后症状有所减轻，应考虑。然而，在范可尼氏综合征治疗的情况下，应迅速无论以前LVD的历史切换。在这种情况下，在肾功能所得改进应迅速显现。

全文:
http://onlinelibrary.wiley.com/doi/10.1111/apt.13659/full