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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. 作者: StephenW 时间: 2016-5-28 21:24
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
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。