替諾福韋阿拉芬酰胺預防高病毒載量母親的圍產期乙肝傳播

StephenW

Tenofovir alafenamide to prevent perinatal hepatitis B transmission in mothers with high viral load: a multicenter, prospective, observational study.

TAF and TDF Prevent HBV Transmission From Mothers With High HBV Loads in China

AASLD The Liver Meeting Digital Experience, November 13-16, 2020

Mark Mascolini

Both tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) taken by pregnant women with an HBV load above 200,000 IU/mL prevented HBV transmission to all newborns in a matched comparison of 232 women in China [1]. All infants also received standard immunoprophylaxis against HBV: 100 IU of hepatitis B immunoglobin and 3 individual 10-μg doses of recombinant HBV vaccine within 12 hours of birth, at 1 month, and at 6 months. TAF also prevented mother-to-child HBV transmission in a separate 71-mother national multicenter study in China [2].

The TAF-TDF comparison enrolled 20- to 40-year-old women pregnant for more than 24 weeks. They all had HBV DNA above 200,000 IU/mL and normal alanine aminotransferase (ALT). The study excluded women who received anti-HBV therapy or treatment to lower ALT and women with evidence of hepatocellular carcinoma, cirrhosis, another hepatitis virus, HIV, or systemic disorders.

Researchers matched 116 mother who chose TDF for prophylaxis to 116 who chose TAF by age (within 1 year), gestational age (within 1 week), and HBeAg status (HBeAg indicates replicating virus that can be transmitted). Women in each matched pair started TDF or TAF within 1 week. Women taking TAF bore 117 infants, and women taking TDF bore 116. All 232 women completed their full course of TAF or TDF from baseline to delivery.

Age averaged a few months over 29 years in both the TAF and TDF group, while gestational age averaged 28.2 weeks in both groups. The groups did not differ in proportions bearing their first child (about three quarters) or in hemoglobin, platelets, ALT, total bilirubin, or creatinine. Fifteen women taking TAF (12.9%) and 14 taking TDF (12.1%) had premature rupture of membranes.

At delivery and 3 and 6 months after delivery, 92% of women in both groups were positive for HBeAg. HBV DNA at delivery averaged 3.5 IU/mL in the TAF group and 3.4 IU/mL in the TDF group. HBV DNA averaged 7.7 IU/mL at 3 months in both the TAF and TDF groups and 7.8 IU/mL at 6 months in both groups. Among infant parameters, the TAF and TDF groups did not differ in weight, height, head circumference, or Apgar score at 1 minute. No infant in either group had congenital defects or malformation. Physical and neurologic development were normal in both groups.

At infant 7-month visits, no infant tested positive for HBsAg in either group, a result indicating none of them had current HBV infection. Almost all infants in both groups tested positive for anti-HBs at 7 months.

For mothers, TAF and TDF had similarly good safety profiles. No mothers stopped TAF because of adverse events. The most frequent TAF adverse event was nausea in 19%.

References
1. Zeng QL, Yu Z, Wang FS. Tenofovir alafenamide to prevent perinatal hepatitis B transmission in mothers with high viral load: a multicenter, prospective, observational study. AASLD The Liver Meeting Digital Experience, November 13-16, 2020. Abstract 160.
2. Ding Y, Cao L, Zhu L, et al. Tenofovir alafenamide fumarate therapy for the prevention of hepatitis B vertical transmission in highly viremic mothers with chronic hepatitis B. AASLD The Liver Meeting Digital Experience, November 13-16, 2020. Abstract 20. (Reported separately by NATAP.)

StephenW

替諾福韋阿拉芬酰胺預防高病毒載量母親的圍產期乙肝傳播：一項多中心，前瞻性和觀察性研究。

TAF和TDF阻止了中國HBV高負荷母親的HBV傳播

AASLD肝臟會議數字體驗，2020年11月13日至16日

馬克·馬斯科利尼

HBV負荷超過200,000 IU / mL的孕婦服用替諾福韋alafenamide（TAF）和替諾福韋二吡呋酯富馬酸酯（TDF）阻止了HBV傳播給所有新生兒[232]。所有嬰兒均在出生後12個月，1個月和6個月內接受了針對HBV的標準免疫預防：100 IU乙型肝炎免疫球蛋白和3份單獨的10μg劑量的重組HBV疫苗。在另一項由中國71位母親組成的全國性多中心研究中，TAF還阻止了母嬰HBV傳播[2]。

TAF-TDF的比較納入了20至40歲懷孕24週以上的女性。他們的HBV DNA均高於200,000 IU / mL，且丙氨酸轉氨酶（ALT）正常。該研究排除了接受抗HBV治療或降低ALT的婦女以及有肝細胞癌，肝硬化，另一種肝炎病毒，HIV或全身性疾病的證據的婦女。

研究人員將116名選擇TDF進行預防的母親與116名選擇了TAF的母親按年齡（1歲以內），胎齡（1週以內）和HBeAg狀況（HBeAg表示可以傳播的複制病毒）配對。每對匹配的女性在1週內開始TDF或TAF。服用TAF的婦女有117名嬰兒，而服用TDF的婦女有116嬰兒。所有232名婦女從基線到分娩都完成了TAF或TDF的整個療程。

TAF和TDF組的平均年齡在29歲以上的幾個月，而兩組的平均胎齡為28.2週。兩組中生第一個孩子的比例（大約四分之三）或血紅蛋白，血小板，ALT，總膽紅素或肌酐的比例無差異。服用TAF的15名女性（佔12.9％）和服用TDF的14名女性（佔12.1％）的胎膜早破。

分娩時以及分娩後3和6個月，兩組中92％的婦女HBeAg陽性。在TAF組中，交貨時的HBV DNA平均為3.5 IU / mL，在TDF組中，平均為3.4 IU / mL。 TAF和TDF組在3個月時的HBV DNA平均為7.7 IU / mL，兩組在6個月時的平均值為7.8 IU / mL。在嬰兒參數中，TAF和TDF組在1分鐘時的體重，身高，頭圍或Apgar評分沒有差異。兩組中的嬰兒均無先天性缺陷或畸形。兩組的身體和神經發育均正常。

在嬰兒接受7個月的隨訪時，兩組嬰兒均未檢測出HBsAg陽性，結果表明他們均未感染HBV。兩組中幾乎所有嬰兒在7個月時抗HBs呈陽性。

對於母親來說，TAF和TDF具有相似的良好安全性。沒有母親因為不良事件而停止TAF。 TAF最常見的不良反應是噁心，佔19％。

參考文獻
1.曾慶良，於忠，王FS。替諾福韋阿拉芬酰胺預防高病毒載量母親的圍產期乙型肝炎傳播：一項多中心，前瞻性和觀察性研究。 AASLD肝臟會議數字體驗，2020年11月13日至16日。摘要160。
2.丁Y，曹力，朱力，等。替諾福韋阿拉芬酰胺富馬酸酯療法可預防高病毒血症慢性乙型肝炎母親的乙型肝炎垂直傳播。AASLD肝臟會議數字體驗，2020年11月13日至16日。摘要20.（由NATAP另行報告）