Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong, China.
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong, China.
Aliment Pharmacol Ther. 2018 Mar;47(6):730-737. doi: 10.1111/apt.14497. Epub 2018 Jan 22.
Safety profile of nucleos(t)ide analogues is an important issue in view of its widespread use for decades in patients with chronic hepatitis B (CHB).
To review and evaluate the latest evidence on the safety profiles of the six approved nucleoside analogues.
Relevant articles related to nucleoside analogue safety were selected for review following extensive language- and date-unrestricted, electronic searches of the literature.
Nephrotoxicity has been well reported in patients receiving older generations of nucleotide analogues, namely adefovir dipivoxil and tenofovir disoproxil fumarate (TDF). Yet risks of renal failure and renal replacement therapy were similar in patients treated with nucleoside analogues versus nucleotide analogues in real-life setting. Bone toxicity is closely related to nucleoside analogue effect on renal proximal tubular and phosphaturia. Real-life data demonstrated increased risk of hip fracture in patients receiving adefovir but not TDF. The newly approved tenofovir alafenamide (TAF) has improved renal and bone safety profiles compared to TDF. Long-term use of nucleoside analogues eg entecavir does not increase the risk of other cancers. Muscular toxicity may be seen in telbivudine-treated patients so regular monitoring is advised. Peripheral neuropathy and lactic acidosis are rare adverse events. Latest international guidelines support the use of TDF, telbivudine and lamivudine during pregnancy; breastfeeding is not contraindicated during TDF therapy.
Long-term safety profile of nucleoside analogues is now better defined with more data from large real-life cohorts and clinical trials with long-term follow-up. The new nucleotide analogue, TAF is now available with favourable renal and bone safety profiles.
鉴于核苷（酸）类似物在慢性乙型肝炎（CHB）患者中已广泛使用数十年，其安全性特征是一个重要问题。
综述和评估已批准的六种核苷类似物的最新安全性特征证据。
通过广泛的无语言和无日期限制的电子文献检索，选择与核苷类似物安全性相关的相关文章进行综述。
在真实环境中，接受阿德福韦酯和富马酸替诺福韦二吡呋酯（TDF）等较老一代核苷酸类似物治疗的患者已充分报道了肾毒性。然而，在接受核苷类似物治疗的患者与接受核苷酸类似物治疗的患者中，肾衰竭和肾脏替代治疗的风险相似。骨毒性与核苷类似物对肾近端小管和磷尿的作用密切相关。真实数据表明，接受阿德福韦酯治疗的患者髋部骨折风险增加，但 TDF 则不然。新批准的替诺福韦艾拉酚胺（TAF）与 TDF 相比，具有改善的肾脏和骨骼安全性特征。长期使用核苷类似物（如恩替卡韦）不会增加其他癌症的风险。替比夫定治疗的患者可能会出现肌肉毒性，因此建议定期监测。周围神经病和乳酸酸中毒是罕见的不良事件。最新的国际指南支持在妊娠期间使用 TDF、替比夫定和拉米夫定；TDF 治疗期间不禁止母乳喂养。
随着来自大型真实队列和长期随访临床试验的更多数据，核苷类似物的长期安全性特征现在得到了更好的定义。新型核苷酸类似物 TAF 具有良好的肾脏和骨骼安全性特征。
