比較Tenofovir alafenamide (TAF) 和Tenofovir disoproxil fumarate (TDF) 藥物對於預防B型肝炎母嬰垂直傳染的成效：系統性回顧統合分析與臨床試驗計畫書

Abstract

研究背景 B型肝炎病毒通常透過血液或體液傳播，尤其主要在生產時由母親傳染給嬰兒，或在兒童年幼時因接觸B型肝炎帶原者之家庭成員而傳播。為了預防B型肝炎母嬰垂直傳染，除了施打三劑B型肝炎疫苗外，施打B型肝炎免疫球蛋白也已用來降低B型肝炎母嬰垂直傳染。然而，即使在上述疫苗政策規範下，B型肝炎病毒量高的孕婦仍有較高的機會發生母嬰垂直傳染。因此，近年針對B型肝炎病毒量高的孕婦，可使用抗病毒藥物降低母嬰垂直傳染的機會。“惠立妥”為現第一線使用之預防母嬰垂直傳染之抗病毒藥物，然而，新藥“韋立得”陸續有相關證據證明，比起“惠立妥”有更低的腎毒性或骨密度變化的風險。但關於懷孕期間使用“韋立得”比起“惠立妥”預防母嬰垂直傳染的有效性及安全性的相關資料仍有限。因此，我們進行了一項系統回顧分析，希望統合有限的資料，比較“韋立得”與“惠立妥”在預防B型肝炎母嬰垂直傳染方面的有效性和安全性。 方法 使用Pubmed、Cochrane library和 Embase資料庫進行搜索，選擇隨機對照臨床試驗或前瞻性研究且受試對象為在懷孕期間任何時間接受“韋立得”或“惠立妥”兩個藥物作為預防母嬰垂直傳染的慢性B型肝炎帶原孕婦及其所生之小孩，透過系統性回顧及統合分析探討使用“韋立得”與“惠立妥”在預防B型肝炎母嬰垂直傳染方面的有效性和安全性。 結果 本研究一共納入了4個研究，一項隨機對照試驗、3項多中心前瞻性研究，共有621名孕婦及628名嬰兒納入分析。其結果顯示，母親服用“韋立得”的嬰兒B型肝炎帶原率（嬰兒6-12個月大時測得表面抗原為陽性）與服用“惠立妥”相似（p=0.45），另外，在母親B型肝炎的病毒量方面，母親服用“韋立得”和服用“惠立妥”在生產時，兩組間無顯著差異，兩個藥物皆可有效降低B型肝炎的病毒量。而在藥物安全性方面，無論對於孕婦或是嬰兒，使用“韋立得”或“惠立妥”所產生的不良事件的機會，兩組間皆無顯著差異。 結論 根據本研究結果顯示，“韋立得”和“惠立妥”兩組，對於孕婦或是嬰兒的安全性和有效性相當。然而，仍需要更多資料證明，使用“韋立得”和“惠立妥”對於孕婦或嬰兒長期的安全性。

Background Hepatitis B virus (HBV) is transmitted by exposure to infected blood or other body fluids. It is mainly transmitted from mother to infant in the perinatal period or from household contacts in early childhood. To prevent mother-to-infant transmission (MTIT), the vaccination program in Taiwan, not only hepatitis B immunoglobulin (HBIG), but HBV vaccine for three doses was already provided to reduce MTIT. However, the MTIT is more likely to occur in pregnant women with high viral load. Therefore, not only vaccination programs but antiviral agents are necessary to prevent MTIT. Tenofovir disoproxil fumarate (TDF) is currently recommended as the first-line drug, while Tenofovir alafenamide (TAF) exhibits a lower risk of renal toxicity or bone density changes than TDF. Nevertheless, there are still few literatures regarding chronic HBV-infected women using TAF versus TDF during pregnancy to prevent MTIT till now. Therefore, we conducted a systematic review and meta-analysis to compare the efficacy and safety of TAF with TDF in preventing MTIT. Methods Pubmed, the Cochrane library, and Embase were searched to identify randomized controlled clinical trials (RCTs) and prospective studies that enrolled pregnant women with chronic HBV infection who received TDF or TAF at any time during pregnancy. Result 4 studies (1 RCT and 3 multi-center prospective studies) that enrolled 621 women and 628 infants were included. The pooled results showed that the MTIT rate (infant was 6-12 months of age, and was noted HBsAg-positive) in the TAF group was similar to the TDF group (p=0.45), and so did the maternal HBV DNA level at delivery. On the other hand, the TAF group had comparable safety profiles to the TDF group. Conclusion Through this meta-analysis, we found that the TAF group had comparable safety and effectiveness profiles as the TDF group. However, we still need to know the long-term safety outcomes for these mothers and infants.