丙酚替诺福韦：新版欧洲/美国慢乙肝指南推荐的一线治疗药物
<div> <section class="xmteditor" style="display:none;" data-tools="新媒体管家" data-label="powered by xmt.cn"></section><section data-role="outer" label="Powered by 135editor.com"><section data-role="outer" label="Powered by 135editor.com"><section><section powered-by="135编辑器" class="_135editor"><section><section><section powered-by="135编辑器"><p></p><section><section><section><section data-role="outer" label="Powered by 135editor.com" style="max-width: 100%;font-size: 16px;box-sizing: border-box !important;word-wrap: break-word !important;"><section data-role="outer" label="Powered by 135editor.com" style="max-width: 100%;box-sizing: border-box !important;word-wrap: break-word !important;"><section style="max-width: 100%;box-sizing: border-box;word-wrap: break-word !important;"><section powered-by="135编辑器" class="" style="max-width: 100%;box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;word-wrap: break-word !important;"><section style="margin-top: 10px;margin-bottom: 10px;max-width: 100%;box-sizing: border-box;word-wrap: break-word !important;"><section style="padding-right: 10px;padding-bottom: 10px;padding-left: 10px;max-width: 100%;box-sizing: border-box;display: inline-block;width: 677px;vertical-align: top;border-style: solid;border-width: 2px;border-radius: 0px;border-color: rgb(138, 176, 240);word-wrap: break-word !important;"><section powered-by="135编辑器" style="max-width: 100%;box-sizing: border-box;word-wrap: break-word !important;"><section style="margin-bottom: 8px;max-width: 100%;box-sizing: border-box;text-align: center;word-wrap: break-word !important;"><section style="max-width: 100%;box-sizing: border-box;display: inline-block;vertical-align: top;word-wrap: break-word !important;"><section style="max-width: 100%;box-sizing: border-box;width: 0px;display: inline-block;vertical-align: top;border-top: 0.8em solid rgb(95, 156, 239);border-right: 0.4em solid rgb(95, 156, 239);word-wrap: break-word !important;border-left: 0.4em solid transparent !important;border-bottom: 0.8em solid transparent !important;"></section><section style="padding-right: 5px;padding-left: 5px;max-width: 100%;box-sizing: border-box;display: inline-block;vertical-align: top;height: 1.6em;line-height: 1.6em;background-color: rgb(95, 156, 239);color: rgb(255, 255, 255);word-wrap: break-word !important;"><p style="max-width: 100%;box-sizing: border-box;min-height: 1em;word-wrap: break-word !important;">编者按</p></section><section style="max-width: 100%;box-sizing: border-box;width: 0px;display: inline-block;vertical-align: top;border-top: 0.8em solid rgb(95, 156, 239);border-left: 0.4em solid rgb(95, 156, 239);word-wrap: break-word !important;border-right: 0.4em solid transparent !important;border-bottom: 0.8em solid transparent !important;"></section></section></section></section><section powered-by="135编辑器" style="max-width: 100%;box-sizing: border-box;word-wrap: break-word !important;"><section style="max-width: 100%;box-sizing: border-box;word-wrap: break-word !important;"><section style="max-width: 100%;box-sizing: border-box;font-size: 14px;line-height: 1.8;color: rgb(58, 160, 230);word-wrap: break-word !important;"><p style="max-width: 100%;box-sizing: border-box;min-height: 1em;word-wrap: break-word !important;"><span style="max-width: 100%;box-sizing: border-box;font-family: Avenir, sans-serif;word-wrap: break-word !important;">丙酚替诺福韦（TAF，韦立得</span><sup style="max-width: 100%;box-sizing: border-box;font-family: Avenir, sans-serif;word-wrap: break-word !important;"></sup><span style="max-width: 100%;box-sizing: border-box;font-family: Avenir, sans-serif;word-wrap: break-word !important;">），是全新一代的口服核苷酸类似物，也被称作为替诺福韦升级版。TAF聽是美国聽FDA聽过去聽10聽年唯一批准上市的慢乙肝口服抗病毒药物，也是新版欧洲和美国慢乙肝诊疗指南推荐的一线治疗药物。本文根据已公布的相关临床数据总结了聽TAF聽聽的特点，希望能给医生的临床工作提供一些便利。</span></p></section></section></section></section></section></section></section></section></section></section></section></section></section></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin-top: 10px;margin-right: 0%;margin-left: 0%;box-sizing: border-box;"><section style="display: inline-block;width: 100%;vertical-align: top;background-color: rgba(242, 166, 166, 0);box-sizing: border-box;"><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="text-align: center;margin: 10px 0%;box-sizing: border-box;"><section style="display: inline-block;width: 100%;vertical-align: top;border-width: 1px;border-radius: 0px;border-style: solid;border-color: rgb(202, 198, 198);padding: 10px;box-sizing: border-box;"><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin-top: 10px;margin-bottom: 10px;box-sizing: border-box;"><section style="display: inline-block;padding-top: 3px;padding-bottom: 3px;border-top: 1px solid rgb(202, 198, 198);border-bottom: 1px solid rgb(202, 198, 198);border-right-color: rgb(202, 198, 198);border-left-color: rgb(202, 198, 198);box-sizing: border-box;"><section style="padding-right: 5px;padding-left: 5px;display: inline-block;background-color: rgb(95, 156, 239);color: rgb(254, 254, 254);box-sizing: border-box;"><p style="box-sizing: border-box;"><strong style="box-sizing: border-box;"></strong><strong style="box-sizing: border-box;">丙</strong><strong style="box-sizing: border-box;">酚替诺福韦（TAF）特有的靶向肝脏机制赋予其高效安全的特征</strong></p><p style="box-sizing: border-box;"><strong style="box-sizing: border-box;"></strong></p></section></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="text-align: justify;color: rgba(10, 9, 9, 0.8);line-height: 1.8;font-size: 14px;box-sizing: border-box;"><p style="white-space: normal;box-sizing: border-box;"><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">TAF聽的体外血浆半衰期达聽90聽min，显著长于聽TDF聽的聽0.4聽min，在血浆中更稳定。TAF聽能直接靶向递送至肝脏，使得在较低剂量时即可达到相似的抗病毒活性、全身暴露减少，因此肾脏和骨骼毒性下降聽</span><sup style="color: rgb(51, 51, 51);font-family: Avenir, sans-serif;box-sizing: border-box;"></sup><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">。1b聽期研究发现，≤聽25聽mg聽的聽TAF聽能达到与聽300聽mg聽的聽TDF聽相似的病毒抑制，但聽TFV聽的暴露减少聽90%聽以上聽</span><sup style="color: rgb(51, 51, 51);font-family: Avenir, sans-serif;box-sizing: border-box;"></sup><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">。对机制的进一步研究聽</span><sup style="color: rgb(51, 51, 51);font-family: Avenir, sans-serif;box-sizing: border-box;"></sup><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">显示，TAF聽能通过多个步骤被肝细胞有效地摄取和活化，使肝细胞内维持高浓度的活性代谢产物替诺福韦双磷酸盐（TFV-DP）。在犬体内的药代动力学研究表明，肝脏能高效摄取聽TAF，摄取率约聽65%</span><sup style="color: rgb(51, 51, 51);font-family: Avenir, sans-serif;box-sizing: border-box;"></sup><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">。</span></p></section></section></section></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin-right: 0%;margin-left: 0%;box-sizing: border-box;"><section style="background-color: rgb(95, 156, 239);height: 4px;box-sizing: border-box;"></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="text-align: center;margin: 10px 0%;box-sizing: border-box;"><section style="display: inline-block;width: 100%;vertical-align: top;border-width: 1px;border-radius: 0px;border-style: solid;border-color: rgb(202, 198, 198);padding: 10px;box-sizing: border-box;"><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin-top: 10px;margin-bottom: 10px;box-sizing: border-box;"><section style="display: inline-block;padding-top: 3px;padding-bottom: 3px;border-top: 1px solid rgb(202, 198, 198);border-bottom: 1px solid rgb(202, 198, 198);border-right-color: rgb(202, 198, 198);border-left-color: rgb(202, 198, 198);box-sizing: border-box;"><section style="padding-right: 5px;padding-left: 5px;display: inline-block;background-color: rgb(95, 156, 239);color: rgb(254, 254, 254);box-sizing: border-box;"><p style="box-sizing: border-box;"><strong style="box-sizing: border-box;"><strong style="color: rgb(254, 254, 254);font-size: 16px;text-align: center;white-space: normal;background-color: rgb(95, 156, 239);box-sizing: border-box;"><strong style="box-sizing: border-box;">丙酚替诺福韦（TAF）</strong>的抗病毒疗效与 TDF 相似</strong></strong></p></section></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="text-align: justify;color: rgba(10, 9, 9, 0.8);line-height: 1.8;font-size: 14px;box-sizing: border-box;"><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;color: rgb(51, 51, 51);font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">TAF 的全球 III 期临床研究聽<sup style="box-sizing: border-box;"></sup>和我国 III 期研究聽<sup style="box-sizing: border-box;"></sup>显示，25聽mg聽的聽TAF聽抑制聽HBV聽复制的作用与聽300聽mg聽富马酸替诺福韦二吡呋酯（TDF）相当。</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;color: rgb(51, 51, 51);font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">全球研究中，治疗聽144聽周时，TAF聽组和聽TDF聽组的病毒学应答率（HBV聽DNA＜29聽IU/mL）在聽HBeAg聽阴性人群分别为聽87%（TAF）和聽85%（TDF），P聽=聽0.71，在聽HBeAg聽阳性人群分别为聽74%（TAF）和聽71%（TDF），P聽=聽0.59，如图聽1。</p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin: 0.5em auto;box-sizing: border-box;"><section style="max-width: 100%;display: inline-block;line-height: 0;border-color: rgb(204, 204, 204);border-width: 8px;border-style: solid;box-sizing: border-box;"></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="color: rgba(62, 62, 62, 0.79);line-height: 1.8;font-size: 12px;box-sizing: border-box;"><p style="box-sizing: border-box;"><span style="font-family: Avenir, sans-serif;box-sizing: border-box;">图 1. TAF 对比 TDF 治疗慢乙肝 III 期研究 144 周的病毒学应答</span></p></section></section></section></section></section></section></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin-right: 0%;margin-left: 0%;box-sizing: border-box;"><section style="background-color: rgb(95, 156, 239);height: 4px;box-sizing: border-box;"></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="text-align: center;margin: 10px 0%;box-sizing: border-box;"><section style="display: inline-block;width: 100%;vertical-align: top;border-width: 1px;border-radius: 0px;border-style: solid;border-color: rgb(202, 198, 198);padding: 10px;box-sizing: border-box;"><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin-top: 10px;margin-bottom: 10px;box-sizing: border-box;"><section style="display: inline-block;padding-top: 3px;padding-bottom: 3px;border-top: 1px solid rgb(202, 198, 198);border-bottom: 1px solid rgb(202, 198, 198);border-right-color: rgb(202, 198, 198);border-left-color: rgb(202, 198, 198);box-sizing: border-box;"><section style="padding-right: 5px;padding-left: 5px;display: inline-block;background-color: rgb(95, 156, 239);color: rgb(254, 254, 254);box-sizing: border-box;"><p style="box-sizing: border-box;"><strong style="font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;"><strong style="caret-color: rgb(254, 254, 254);color: rgb(254, 254, 254);font-size: 16px;text-align: center;white-space: normal;box-sizing: border-box;">丙酚替诺福韦（TAF）</strong>具有更高的生化学应答</strong></p></section></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="text-align: justify;color: rgba(10, 9, 9, 0.8);line-height: 1.8;font-size: 14px;box-sizing: border-box;"><p style="white-space: normal;box-sizing: border-box;"><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">TAF聽与聽TDF聽相比，能取得更高的聽ALT聽复常率（男性聽≤聽35聽U/L，女性聽≤聽25聽U/L），治疗为聽71%（HBeAg聽阴性）和聽64%（HBeAg聽阳性），TDF聽组为聽59%（HBeAg聽阴性）和聽53%（HBeAg聽阳性），P聽值为聽0.052（HBeAg聽阴性人群）和聽0.01（HBeAg聽阳性人群）。如图聽2。</span></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin: 0.5em auto;box-sizing: border-box;"><section style="max-width: 100%;display: inline-block;line-height: 0;border-color: rgb(204, 204, 204);border-width: 8px;border-style: solid;box-sizing: border-box;"></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="color: rgba(62, 62, 62, 0.79);line-height: 1.8;font-size: 12px;box-sizing: border-box;"><p style="box-sizing: border-box;"><span style="font-family: Avenir, sans-serif;box-sizing: border-box;">图 2. TAF 对比 TDF 治疗慢乙肝 III 期研究 144 周的生化学应答</span></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="text-align: left;box-sizing: border-box;"><p style="box-sizing: border-box;"><br/></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="text-align: justify;color: rgba(10, 9, 9, 0.8);line-height: 1.8;font-size: 14px;box-sizing: border-box;"><p style="white-space: normal;box-sizing: border-box;"><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">最近对聽ALT聽复常与肝癌风险的关系得到了很多热议和关注。例如，AASLD2018聽上韩国学者报告聽</span><sup style="color: rgb(51, 51, 51);font-family: Avenir, sans-serif;box-sizing: border-box;"></sup><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">，ALT聽复常是预测慢乙肝肝癌发展的独立替代性指标。同期来自欧洲的研究提示，慢乙肝治疗聽1聽年时聽ALT聽是否恢复正常与聽HCC聽独立相关聽</span><sup style="color: rgb(51, 51, 51);font-family: Avenir, sans-serif;box-sizing: border-box;"></sup><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">。我国香港学者的研究表明，慢乙肝治疗聽1聽年时聽ALT聽是否恢复正常与聽HCC聽独立相关聽</span><sup style="color: rgb(51, 51, 51);font-family: Avenir, sans-serif;box-sizing: border-box;"></sup><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">。而在聽2018聽年年底引起热议的发表于聽JAMA聽Oncology聽的文章中聽</span><sup style="color: rgb(51, 51, 51);font-family: Avenir, sans-serif;box-sizing: border-box;"></sup><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">，TDF聽治疗后比恩替卡韦能显著降低更多肝癌风险（推测核苷酸类似物产生的干扰素λ3聽样作用可能是其中一个原因），而分析显示，TDF聽治疗的聽ALT聽复常率更高，并且聽ALT聽是影响聽HCC聽发生的因素。上述结果的临床意义值得借鉴和参考，也期待中国大陆的研究数据能够进一步探索阐明。</span></p></section></section></section></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin-right: 0%;margin-left: 0%;box-sizing: border-box;"><section style="background-color: rgb(95, 156, 239);height: 4px;box-sizing: border-box;"></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="text-align: center;margin: 10px 0%;box-sizing: border-box;"><section style="display: inline-block;width: 100%;vertical-align: top;border-width: 1px;border-radius: 0px;border-style: solid;border-color: rgb(202, 198, 198);padding: 10px;box-sizing: border-box;"><section style="box-sizing: border-box;" powered-by="135编辑器"><section style="margin-top: 10px;margin-bottom: 10px;box-sizing: border-box;"><section style="display: inline-block;padding-top: 3px;padding-bottom: 3px;border-top: 1px solid rgb(202, 198, 198);border-bottom: 1px solid rgb(202, 198, 198);border-right-color: rgb(202, 198, 198);border-left-color: rgb(202, 198, 198);box-sizing: border-box;"><section style="padding-right: 5px;padding-left: 5px;display: inline-block;background-color: rgb(95, 156, 239);color: rgb(254, 254, 254);box-sizing: border-box;"><p style="box-sizing: border-box;"><strong style="font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;"><strong style="caret-color: rgb(254, 254, 254);color: rgb(254, 254, 254);font-size: 16px;text-align: center;white-space: normal;box-sizing: border-box;">丙酚替诺福韦（TAF）</strong>治疗 144 周「零」耐药</strong></p></section></section></section></section><section style="box-sizing: border-box;" powered-by="135编辑器"><section style="box-sizing: border-box;"><section style="text-align: justify;color: rgba(6, 5, 5, 0.84);line-height: 1.8;font-size: 14px;box-sizing: border-box;"><p style="white-space: normal;box-sizing: border-box;"><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">TAF 全球 III 期临床试验聽</span><sup style="color: rgb(51, 51, 51);font-family: Avenir, sans-serif;box-sizing: border-box;"></sup><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">聽中，治疗聽144聽周未检测到与聽TAF聽耐药有关的变异，突变病毒的表型分析，TAF聽的敏感性未见下降，意味着聽TAF聽治疗聽144聽周保持「零」耐药。我国慢乙肝患者治疗聽96聽周同样未发现耐药。</span></p></section></section></section></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin-right: 0%;margin-left: 0%;box-sizing: border-box;"><section style="background-color: rgb(95, 156, 239);height: 4px;box-sizing: border-box;"></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="text-align: center;margin: 10px 0%;box-sizing: border-box;"><section style="display: inline-block;width: 100%;vertical-align: top;border-width: 1px;border-radius: 0px;border-style: solid;border-color: rgb(202, 198, 198);padding: 10px;box-sizing: border-box;"><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin-top: 10px;margin-bottom: 10px;box-sizing: border-box;"><section style="display: inline-block;padding-top: 3px;padding-bottom: 3px;border-top: 1px solid rgb(202, 198, 198);border-bottom: 1px solid rgb(202, 198, 198);border-right-color: rgb(202, 198, 198);border-left-color: rgb(202, 198, 198);box-sizing: border-box;"><section style="padding-right: 5px;padding-left: 5px;display: inline-block;background-color: rgb(95, 156, 239);color: rgb(254, 254, 254);box-sizing: border-box;"><p style="box-sizing: border-box;"><strong style="font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;"><strong style="caret-color: rgb(254, 254, 254);color: rgb(254, 254, 254);font-size: 16px;text-align: center;white-space: normal;box-sizing: border-box;">丙酚替诺福韦（TAF）</strong>的肾脏功能及骨密度的影响小于 TDF</strong></p></section></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="text-align: justify;color: rgba(6, 5, 5, 0.84);line-height: 1.8;font-size: 14px;box-sizing: border-box;"><p style="white-space: normal;box-sizing: border-box;"><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">TAF聽对比聽TDF聽治疗慢乙肝的聽III聽期临床试验聽48聽周、96聽周和聽144聽周的结果均一致显示，TAF聽治疗的肾脏安全性和骨骼代谢的相关参数均显著优于聽TDF。与聽TDF聽组相比，TAF聽治疗对肾脏功能的影响显著更小，eGFR</span><sub style="color: rgb(51, 51, 51);font-family: Avenir, sans-serif;box-sizing: border-box;">CG</sub><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">的下降更少（图聽3），近端小管蛋白尿标志物的变化更小。</span></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin: 0.5em auto;box-sizing: border-box;"><section style="max-width: 100%;display: inline-block;line-height: 0;border-color: rgb(204, 204, 204);border-width: 8px;border-style: solid;box-sizing: border-box;"></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="color: rgba(62, 62, 62, 0.79);line-height: 1.8;font-size: 12px;box-sizing: border-box;"><p style="box-sizing: border-box;"><span style="font-family: Avenir, sans-serif;box-sizing: border-box;">图 3. TAF 对比 TDF 治疗慢乙肝 III 期研究 144 周的 eGFR 变化</span></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="text-align: left;box-sizing: border-box;"><p style="box-sizing: border-box;"><br/></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="text-align: justify;color: rgba(6, 5, 5, 0.84);line-height: 1.8;font-size: 14px;box-sizing: border-box;"><p style="white-space: normal;box-sizing: border-box;"><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">同样，TAF聽治疗对骨密度的影响也显著更小，治疗聽3聽年，TAF聽组的脊柱和髋关节的聽BMD聽变化轻微，而聽TDF聽组呈明显下降（图聽4）。</span></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin: 0.5em auto;box-sizing: border-box;"><section style="max-width: 100%;display: inline-block;line-height: 0;border-color: rgb(204, 204, 204);border-width: 8px;border-style: solid;box-sizing: border-box;"></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="color: rgba(62, 62, 62, 0.79);line-height: 1.8;font-size: 12px;box-sizing: border-box;"><p style="box-sizing: border-box;"><span style="font-family: Avenir, sans-serif;box-sizing: border-box;">图 4. TAF 对比 TDF 治疗慢乙肝 III 期研究 144 周的骨密度变化</span></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="text-align: left;box-sizing: border-box;"><p style="box-sizing: border-box;"><br/></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="text-align: justify;color: rgba(6, 5, 5, 0.84);line-height: 1.8;font-size: 14px;box-sizing: border-box;"><p style="white-space: normal;box-sizing: border-box;"><span style="color: #333333;font-family: Avenir, sans-serif;box-sizing: border-box;">不仅如此，TDF聽治疗的患者换用聽TAF聽后，肾脏和骨骼的安全性指标均持续改善，说明原本受到影响的肾脏功能和骨骼代谢均有所恢复。</span></p></section></section></section></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin-right: 0%;margin-left: 0%;box-sizing: border-box;"><section style="background-color: rgb(95, 156, 239);height: 4px;box-sizing: border-box;"></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="text-align: center;margin: 10px 0%;box-sizing: border-box;"><section style="display: inline-block;width: 100%;vertical-align: top;border-width: 1px;border-radius: 0px;border-style: solid;border-color: rgb(202, 198, 198);padding: 10px;box-sizing: border-box;"><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin-top: 10px;margin-bottom: 10px;box-sizing: border-box;"><section style="display: inline-block;padding-top: 3px;padding-bottom: 3px;border-top: 1px solid rgb(202, 198, 198);border-bottom: 1px solid rgb(202, 198, 198);border-right-color: rgb(202, 198, 198);border-left-color: rgb(202, 198, 198);box-sizing: border-box;"><section style="padding-right: 5px;padding-left: 5px;display: inline-block;background-color: rgb(95, 156, 239);color: rgb(254, 254, 254);box-sizing: border-box;"><p style="box-sizing: border-box;"><strong style="font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;"><strong style="caret-color: rgb(254, 254, 254);color: rgb(254, 254, 254);font-size: 16px;text-align: center;white-space: normal;box-sizing: border-box;">丙酚替诺福韦（TAF）</strong>整体安全性和耐受性好，适用人群更广</strong></p></section></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="text-align: justify;color: rgba(6, 5, 5, 0.84);line-height: 1.8;font-size: 14px;box-sizing: border-box;"><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;color: rgb(51, 51, 51);font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">除肾脏功能及骨密度的影响更小外，TAF 治疗慢乙肝的整体安全性和耐受性好，绝大部分不良事件为轻～中度聽<sup style="box-sizing: border-box;"></sup>。</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;color: rgb(51, 51, 51);font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">因应用 TDF 时曾有过乳酸性酸中毒和伴脂肪变性的严重肝肿大病例报道聽<sup style="box-sizing: border-box;"></sup>，TAF聽上市之初聽FDA聽也就这两种情况在聽TAF聽标签中做出了黑框警告。TAF聽上市不到半年，2017聽年聽4聽月，美国聽FDA聽同意取消了这部分黑框警告的内容聽<sup style="box-sizing: border-box;"></sup>，目前在中国已经获批的聽TAF聽说明书中，没有黑框警告。但说明书中也提到，任何患者的临床或实验室结果如果提示使用聽TAF聽治疗过程中，如有乳酸性酸中毒或显著的肝毒性（可能包括肝肿大和脂肪变性，即便转氨酶没有显著升高），应当暂停聽TAF聽治疗。</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;color: rgb(51, 51, 51);font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">此外，TAF 用于 HBV 母婴阻断的相关临床研究正在进行中，目前数据尚不充分（少于 300 例），但根据说明书中对于生育、生殖的动物研究数据以及 TDF 的母婴阻断数据，TAF 说明书中建议如有需要，可以考虑在妊娠期间使用聽<sup style="box-sizing: border-box;"></sup>。</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;color: rgb(51, 51, 51);font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">TAF 卓越的安全性还体现在聽<sup style="box-sizing: border-box;"></sup>：</p><p style="white-space: normal;box-sizing: border-box;"><br/></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="text-align: justify;line-height: 1.8;font-size: 14px;box-sizing: border-box;"><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">●聽聽聽无需针对年龄为聽65聽岁及以上的患者调整剂量。</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">●聽聽聽聽轻、中、重度肾功能不全患者无需调整剂量。</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">●聽聽聽聽没有观察到聽TAF聽治疗的患者出现近端肾小管病变或范可尼综合征。</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">●聽聽聽聽无需针对肝功能损害患者调整剂量。</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">●聽聽聽聽关于生殖毒性，动物研究未发现聽TAF聽存在直接或间接有害影响。</p></section></section></section></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin-right: 0%;margin-left: 0%;box-sizing: border-box;"><section style="background-color: rgb(95, 156, 239);height: 4px;box-sizing: border-box;"></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="text-align: center;margin: 10px 0%;box-sizing: border-box;"><section style="display: inline-block;width: 100%;vertical-align: top;border-width: 1px;border-radius: 0px;border-style: solid;border-color: rgb(202, 198, 198);padding: 10px;box-sizing: border-box;"><section style="box-sizing: border-box;" powered-by="135编辑器"><section style="margin-top: 10px;margin-bottom: 10px;box-sizing: border-box;"><section style="display: inline-block;padding-top: 3px;padding-bottom: 3px;border-top: 1px solid rgb(202, 198, 198);border-bottom: 1px solid rgb(202, 198, 198);border-right-color: rgb(202, 198, 198);border-left-color: rgb(202, 198, 198);box-sizing: border-box;"><section style="padding-right: 5px;padding-left: 5px;display: inline-block;background-color: rgb(95, 156, 239);color: rgb(255, 255, 255);font-size: 17px;box-sizing: border-box;"><p style="box-sizing: border-box;"><strong style="box-sizing: border-box;">指南推荐</strong></p></section></section></section></section><section style="box-sizing: border-box;" powered-by="135编辑器"><section style="box-sizing: border-box;"><section style="text-align: justify;font-size: 14px;line-height: 1.8;box-sizing: border-box;"><p style="white-space: normal;box-sizing: border-box;"><span style="font-family: Avenir, sans-serif;box-sizing: border-box;">在最新 AASLD</span><sup style="font-family: Avenir, sans-serif;box-sizing: border-box;"></sup><span style="font-family: Avenir, sans-serif;box-sizing: border-box;">聽和 EASL 慢乙肝指南聽</span><sup style="font-family: Avenir, sans-serif;box-sizing: border-box;"></sup><span style="font-family: Avenir, sans-serif;box-sizing: border-box;">中，TAF聽作为一线口服抗病毒药物得到推荐。并且，伴肾功能不全或骨病或存在肾功能不全或骨病风险的患者应考虑使用聽TAF聽或聽ETV，而不是聽TDF。正在使用聽TDF聽治疗的患者若有潜在的肾脏损害或骨病或有肾损害或骨病风险，应考虑转换至聽ETV聽或聽TAF（如果既往有核苷类似物暴露史，应选择聽TAF）。</span></p></section></section></section><section style="box-sizing: border-box;" powered-by="135编辑器"><section style="margin: 0.5em auto;box-sizing: border-box;"><section style="max-width: 100%;display: inline-block;line-height: 0;border-color: rgb(204, 204, 204);border-width: 8px;border-style: solid;box-sizing: border-box;"></section></section></section></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="box-sizing: border-box;"><p style="box-sizing: border-box;"><br/></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="text-align: center;box-sizing: border-box;"><section style="display: inline-block;width: 100%;height: 240px;vertical-align: top;overflow-y: auto;box-sizing: border-box;-webkit-overflow-scrolling: touch;"><section style="overflow-x: hidden;box-sizing: border-box;"><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="margin-top: 20px;margin-right: 0%;margin-left: 0%;box-sizing: border-box;"><section style="display: inline-block;border-width: 2px;border-style: solid;border-color: rgba(9, 9, 9, 0.16);padding: 0.1em 0.3em;color: rgba(62, 62, 62, 0.79);text-align: justify;font-size: 12px;line-height: 1.6;box-sizing: border-box;"><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">参考文献</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">1.聽聽聽聽聽聽聽聽聽聽Terrault聽NA,聽Lok聽AS,聽McMahon聽BJ,聽et聽al.聽Update聽on聽Prevention,聽Diagnosis,聽and聽Treatment聽and聽of聽Chronic聽Hepatitis聽B:聽AASLD聽2018聽Hepatitis聽B聽Guidance.聽Hepatology.聽2018,聽https://doi.org/10.1002/hep.29800</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">2.聽聽聽聽聽聽聽聽聽聽Agarwal聽K,聽Fung聽SK,聽Nguyen聽TT,聽et聽al.聽Twenty-eight聽day聽safety,聽antiviral聽activity,聽and聽pharmacokinetics聽of聽tenofovir聽alafenamide聽for聽treatment聽of聽chronic聽hepatitis聽B聽infection.聽J聽Hepatol聽2014;62:533–540.</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">3.聽聽聽聽聽聽聽聽聽聽Murakami聽E,聽Wang聽T,聽Park聽YJ,聽et聽al.聽Implications聽of聽Efficient聽Hepatic聽Delivery聽by聽Tenofovir聽Alafenamide聽(GS-7340)聽for聽Hepatitis聽B聽Virus聽Therapy.聽Antimicrob聽Agents聽Chemoth.聽2015;59(6)：3563-3569</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">4.聽聽聽聽聽聽聽聽聽聽Babusis聽D,聽Phan聽TK,聽Lee聽WA,聽et聽al.聽Mechanism聽for聽effective聽lymphoid聽cell聽and聽tissue聽loading聽following聽oral聽administration聽of聽nucleotide聽prodrug聽GS-7340.聽Mol聽Pharm聽2013.聽10:459–466.</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">5.聽聽聽聽聽聽聽聽聽 Chan HL, Lim YS, Seto WK, et al. Three Year Efficacy and Safety of Tenofovir Alafenamide (TAF) Compared to Tenofovir Disoproxil Fumarate (TDF) in Hbeag-Negative and Hbeag-Positive Patients with Chronic Hepatitis B. AASLD2018 Poster 381.</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">6.聽聽聽聽聽聽聽聽聽聽聽Hou聽JL,聽Zhang聽LL,聽Duan聽ZP,聽et聽al.聽A聽Phase聽3聽Study聽Comparing聽Tenofovir聽Alafenamide聽With聽Tenofovir聽Disoproxil聽Fumarate聽in聽Patients聽From聽China聽With聽HBeAg-Positive,聽Chronic聽Hepatitis聽B:聽Efficacy聽and聽Safety聽Results聽at聽Week聽48.聽APASL2018.聽HBV-C82</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">7.聽聽聽聽聽聽聽聽聽聽聽Ning聽Q,聽Duan聽ZP,聽Chen聽Y,聽et聽al.聽A聽Phase聽3聽Study聽Comparing聽Tenofovir聽Alafenamide聽With聽Tenofovir聽Disoproxil聽Fumarate聽in聽Patients聽From聽China聽With聽HBeAg-Negative,聽Chronic聽Hepatitis聽B:聽Efficacy聽and聽Safety聽Results聽at聽Week聽48.聽APASL2018.聽O-HBV-12.</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">8.聽聽聽聽聽聽聽聽聽 Choi J, Lim YS, Han SB, et al. Comprehensive Analysis for the Impact of on-Treatment Intermediate Endpoints on Outcomes of Hbeag (+) Chronic Hepatitis B AASLD 2018, Oral 267.</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">9.聽聽聽聽聽聽聽聽聽 Papatheodoridis GV, et al. ALT Levels and Risk of Hepatocellular Carcinoma (HCC) in Caucasian Chronic Hepatitis B (CHB) Patients Under Long-Term Therapy with Entecavir (ETV) or Tenofovir Disoproxil Fumarate (TDF). AASLD 2018, Oral 265.</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">10.聽聽聽聽聽聽Wong聽GL,聽Chan聽HL,聽Tse聽YK,聽et聽al.聽Normal聽on-treatment聽ALT聽during聽antiviral聽treatment聽is聽associated聽with聽a聽lower聽risk聽of聽hepatic聽events聽in聽patients聽with聽chronic聽hepatitis聽B.聽J聽Hepatol.聽2018聽Oct;69(4):793-802.聽</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">11.聽聽聽聽聽 Choi J, Kim HJ, Lee J, et al. Risk of Hepatocellular Carcinoma in Patients Treated With Entecavir vs Tenofovir for Chronic Hepatitis B A Korean Nationwide Cohort Study.JAMA ONcology. 2018. Sep 27</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">12.聽聽聽聽聽 Chan HL, Marcellin P, Pan CQ, et al. No Resistance to Tenofovir Alafenamide Detected through 144 Weeks of Treatment in Patients with Chronic Hepatitis B. AASLD2018. Poster 386.</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">13.聽聽聽聽聽 富马酸丙酚替诺福韦片（韦立得）产品说明书. 2018 年版</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">14.聽聽聽聽聽聽Gilead聽Sciences.聽Prescribing聽information:聽VIREAD聽(tenofovir聽disoproxil聽fumarate).聽https://www.gilead.com/～/media/files/pdfs/medicines/liver-disease/viread/viread_pi.pdf?la聽=聽en</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">15.聽聽聽聽聽聽Gilead聽Sciences.聽Prescribing聽information:聽VEMLIDY聽(tenofovir聽alafenamide).聽https://www.gilead.com/～/media/files/pdfs/medicines/liver-disease/vemlidy/vemlidy_pi.pdf?la聽=聽en</p><p style="margin-top: 5px;padding-bottom: 25px;overflow-wrap: break-word;font-family: Avenir, sans-serif;white-space: normal;box-sizing: border-box;">16.聽聽聽聽聽聽European聽Association聽for聽the聽Study聽of聽the聽Liver.聽EASL聽2017聽Clinical聽Practice聽Guidelines聽on聽the聽management聽of聽hepatitis聽B聽virus聽infection.聽J聽Hepatol聽(2017),聽http://dx.doi.org/10.1016/j.jhep.2017.03.021</p></section></section></section></section></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="box-sizing: border-box;"><p style="box-sizing: border-box;"><br/></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="text-align: right;font-size: 14px;color: rgba(10, 9, 9, 0.8);box-sizing: border-box;"><p style="box-sizing: border-box;"><span style="box-sizing: border-box;">*</span><span style="box-sizing: border-box;">本文仅供医学专业人士阅读</span><br style="box-sizing: border-box;"/></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="box-sizing: border-box;"><p style="box-sizing: border-box;"><br/></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="font-size: 14px;box-sizing: border-box;"><p style="text-align: right;box-sizing: border-box;"><span style="color: rgba(5, 5, 5, 0.62);box-sizing: border-box;">责编：仇道虹</span><br style="box-sizing: border-box;"/></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="box-sizing: border-box;"><p style="box-sizing: border-box;"><br/></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="font-size: 14px;color: rgba(5, 5, 5, 0.62);box-sizing: border-box;"><p style="text-align: right;box-sizing: border-box;">封面图来源：吉利德科学<br style="box-sizing: border-box;"/></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="box-sizing: border-box;"><p style="box-sizing: border-box;"><br/></p></section></section></section><section style="box-sizing: border-box;border-width: 0px;border-style: none;border-color: initial;" powered-by="135编辑器" class="_135editor"><section style="box-sizing: border-box;"><section style="text-align: right;font-size: 14px;color: rgba(5, 5, 5, 0.62);box-sizing: border-box;"><p style="box-sizing: border-box;">插图来源：吉利德科学</p></section></section></section></section></section></section> </div>
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