慢性B型肝炎患者服用Tenofovir Alafenamide治療之療效和安全性—系統性回顧和統合分析

背景與目的：慢性B型肝炎（chronic hepatitis B, CHB）患者若未接受治療，很可能會併發嚴重的併發症。目前治療CHB患者療效最佳的藥物為Tenofovir disoproxil fumarate（TDF），但長期服用會有較高骨密度流失及腎毒性反應。Tenofovir alafenamide（TAF）為Tenofovir的新型藥物，過去用以治療HIV患者的臨床試驗中，顯示與TDF相比，效果相似但安全性較佳。TAF已經開始用於治療一般族群的慢性B型肝炎，安全性需要有更robust的實證資料。本研究旨在探討在治療CHB患者時，TAF是否較TDF，有較好的療效以及更佳的安全性。研究方法：利用PubMed、Cochrane和Embase進行TDF和TAF比較的隨機對照試驗文獻搜尋，搜尋日至2022年3月前出版之英文文獻。統合分析以random-effects model估算療效和安全性，統計軟體選用Review Manager Version 5.4。研究結果：本研究共收錄4篇文獻，在療效部分，TAF相較於TDF在HBV DNA<29 IU/ml (RR=1.00, 95%CI= 0.96-1.03)和HBeAg消失(RR=1.19, 95%CI= 0.95-1.50)未達統計上顯著差異；HBeAg血清學轉換則有統計顯著差異(RR=1.39，95%CI= 1.04-1.83)。在髖骨密度與脊骨密度變化，和血清肌酸酐濃度變化之安全性指標，TAF變化程度皆較TDF小，TAF較TDF有較佳的安全性。結論：本研究結果顯示在治療CHB患者上TAF與TDF相比，在療效結果具非劣性，安全性結果則為TAF優於TDF。因此TAF有機會可以作為臨床上的另一種選擇，未來也建議應使用真實世界的資料進行長期慢性副作用的驗證。  Background and purpose: Nowadays, the most effective drug for the treatment of chronic hepatitis B (CHB) patients is Tenofovir disoproxil fumarate (TDF), how-ever long-term use will lead to high bone density loss and nephrotoxicity. Tenofovir alafenamide (TAF) is a noval drug of Tenofovir. In the past clinical trials for the treatment of HIV patients, it has shown similar effects but better safety than TDF. TAF has been used to treat CHB in the general population, but more robust evidence is needed for safety. This study aims to investigate whether TAF has better efficacy and better safety than TDF in the treatment of CHB patients. Methods: PubMed, Cochrane and Embase were used to conduct a literature search of randomized con-trolled trials comparing TDF and TAF, and the English language literature published by March 2022 was searched. Meta-analysis used random-effects model to estimate efficacy and safety, and the statistical software was Review Manager Version 5.4. Results: A total of four articles were included in this study. In the efficacy, TAF com-pared with TDF in HBV DNA<29 IU/ml (RR=1.00, 95%CI=0.96-1.03) and HBeAg loss (RR=1.19, 95 %CI=0.95-1.50) was not statistically significant; HBeAg serocon-version was statistically significant (RR=1.39, 95%CI=1.04-1.83). In the safety indi-cators of changes in hip BMD and spine BMD, and changes in serum creatinine con-centration, the degree of change in TAF was smaller than TDF, and TAF had better safety than TDF. Conclusion: The results of this study show that TAF is non-inferior to TDF in the treatment of CHB patients in terms of efficacy outcomes and TAF is superior to TDF in safety outcomes. Therefore, TAF has the opportunity to be used as another clinical option.