Safety of withdrawal during treatment with tenofovir disoproxil of mothers and infants at various time-points

doi:10.3877/cma.j.issn.1674-1358.2019.01.003

Abstract

Abstract:

Objective

To investigate the safety of different withdraw timepoint of tenofovir disoproxil (TDF) for pregnant women with high hepatitis B virus (HBV) DNA load in blocking mother-to-child transmission of HBV.

Methods

From January 2015 to December 2017, a total of 109 pregnant women with HBsAg positive and immunoresistance were recruited from Shenzhen Third People’s Hospital, all patients were treated with TDF at 24-28 weeks of gestation, who were divided into two groups according to simple randomized grouping method: withdrawal immediately after delivery group (58 cases) and withdrawal 4-12 weeks after delivery group (51 cases). The levels of HBV DNA and ALT were measured quantitatively at 4 weeks, 8 weeks, 12 weeks after antiviral therapy, at withdrawal and 4 weeks, 8 weeks, 12 weeks and 24 weeks after TDF discontinuation in both groups. Quantitative HBsAg and HBsAb levels of newborns at 4 weeks after birth were detected.

Results

HBV DNA levels of all pregnant women before delivery were significantly lower than those of the baseline (withdrawal immediately after delivery group: Z = 8.459, P < 0.001; withdrawal 4-12 weeks after delivery group: Z = 7.760, P < 0.001). HBV DNA levels at the timepoint of withdrawal between the two groups were significantly different (Z = 2.242, P = 0.025). The difference of HBV DNA level 4 weeks after withdrawal between the two groups was not significant (Z = 1.041, P = 0.298), and no significant differences were found compared with the baseline levels (withdrawal immediately after delivery group: Z = 0.155, P = 0.877; withdrawal at 4-12 weeks after delivery group: Z = 0.376, P = 0.707). The difference of postpartum ALT levels between the two groups following up until 24 weeks after withdrawal was not significantly different (χ² = 1.319, P = 0.251). The median timepoint of ALT elevation of both groups was 4 weeks after withdrawal, with no significant difference (Z = 0.196, P = 0.844). The level of ALT increase during pregnancy may cause ALT increase after delivery, but it is not an independent risk factor. Total of 20 newborns were quantitatively detected for peripheral blood HBsAg and HBsAb at 4 weeks postpartum, all of them were HBsAg negative and successfully produced protective antibody.

Conclusions

TDF application in middle and late pregnancy could effectively block HBV transmission from mother to child. Following up for 24 weeks showed that there was no difference in postpartum safety between postpartum withdrawal and delayed withdrawal. Newborns produce protective antibody 4 weeks after birth and breast feeding was safe.

Key words: Tenofovir disoproxil, Hepatitis B virus, Mother-to-child transmission, Withdrawal, Safety

Ling Peng, Liuqing Yang, Tingting Peng, Jinghan Peng, Jing Yuan, Feng Chen, Zhenghua Ma, Yingxia Liu. Safety of withdrawal during treatment with tenofovir disoproxil of mothers and infants at various time-points[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2019, 13(01): 12-18.

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References 25

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组别	例数	年龄（岁，±s）	乙型肝炎家族史[例（%）]	分娩史[例（%）]	HBsAg（log₁₀IU/ml）^a
分娩时停药组	50	28.57 ± 3.41	22（44.00）	17（34.00）	4.54（4.36～4.68）
分娩后4～12周停药组	41	28.72 ± 4.08	18（43.90）	14（34.14）	4.48（3.72～4.61）
统计量	?	t = －0.075	χ²= 0.000	χ² = 0.000	Z =－1.334
P值	?	0.941	0.993	0.988	0.182
组别	例数	HBeAg（S/CO）^a	HBV DNA（log₁₀IU/ml）^a	基线ALT（U/L）^a
分娩时停药组	50	1 389.92（1 181.37～1 541.41）	8.09（7.55～8.23）	22.50（15.00～32.00）
分娩后4～12周停药组	41	1 406.84（1 221.23～1 536.65）	7.87（7.54～8.23）	21.00（12.00～35.00）
统计量	?	Z=－0.180	Z=－0.890	Z=－0.184
P值	?	0.857	0.373	0.854

组别	例数	年龄（岁，±s）	乙型肝炎家族史[例（%）]	分娩史[例（%）]	HBsAg（log₁₀IU/ml）^a
分娩时停药组	50	28.57 ± 3.41	22（44.00）	17（34.00）	4.54（4.36～4.68）
分娩后4～12周停药组	41	28.72 ± 4.08	18（43.90）	14（34.14）	4.48（3.72～4.61）
统计量	?	t = －0.075	χ²= 0.000	χ² = 0.000	Z =－1.334
P值	?	0.941	0.993	0.988	0.182
组别	例数	HBeAg（S/CO）^a	HBV DNA（log₁₀IU/ml）^a	基线ALT（U/L）^a
分娩时停药组	50	1 389.92（1 181.37～1 541.41）	8.09（7.55～8.23）	22.50（15.00～32.00）
分娩后4～12周停药组	41	1 406.84（1 221.23～1 536.65）	7.87（7.54～8.23）	21.00（12.00～35.00）
统计量	?	Z=－0.180	Z=－0.890	Z=－0.184
P值	?	0.857	0.373	0.854

组别	例数	产后4周ALT水平升高[例（%）]	停药后24周ALT水平升高[例（%）]	ALT水平升高出现时间[周，M（25%～75% IQR）]
分娩时停药组	50	13（26.00）	22（44.00）	4.00（4.00～8.00）
分娩后4～12周停药组	41	5（12.20）	23（56.10）	4.00（4.00～8.00）
统计量	?	χ²= 2.067	χ²= 1.319	Z = 0.196
P值	?	0.151	0.251	0.844
组别	例数	ALT水平最高值[U/L，M（25%～75% IQR）]	停药后24周ALT水平升高程度[例（%）]
组别	例数	ALT水平最高值[U/L，M（25%～75% IQR）]	轻度	中度
分娩时停药组	50	74.50（59.00～103.50）	11（50.00）	11（50.00）
分娩后4～12周停药组	41	69.00（60.00～98.00）	13（56.52）	10（43.48）
统计量	?	Z = 0.068	χ²= 0.192
P值	?	0.946	0.661

组别	例数	产后4周ALT水平升高[例（%）]	停药后24周ALT水平升高[例（%）]	ALT水平升高出现时间[周，M（25%～75% IQR）]
分娩时停药组	50	13（26.00）	22（44.00）	4.00（4.00～8.00）
分娩后4～12周停药组	41	5（12.20）	23（56.10）	4.00（4.00～8.00）
统计量	?	χ²= 2.067	χ²= 1.319	Z = 0.196
P值	?	0.151	0.251	0.844
组别	例数	ALT水平最高值[U/L，M（25%～75% IQR）]	停药后24周ALT水平升高程度[例（%）]
组别	例数	ALT水平最高值[U/L，M（25%～75% IQR）]	轻度	中度
分娩时停药组	50	74.50（59.00～103.50）	11（50.00）	11（50.00）
分娩后4～12周停药组	41	69.00（60.00～98.00）	13（56.52）	10（43.48）
统计量	?	Z = 0.068	χ²= 0.192
P值	?	0.946	0.661

临床资料		ALT水平正常组（46例）	ALT水平升高组（45例）	统计量	P值
年龄（±s，岁）		29.23 ± 3.95	28.00 ± 3.34	t = 1.613	0.110
乙型肝炎家族史[例（%）]		17（37.00）	23（51.11）	χ²= 1.850	0.174
分娩史[例（%）]		14（30.43）	17（37.78）	χ²= 0.546	0.460
分娩方式[例（%）]		?	?	χ²= 0.088	0.767
?	顺产	31（67.39）	29（64.44）	?	?
?	剖宫产	15（32.61）	16（35.56）	?	?
基线水平		?	?	?	?
?	HBsAg（log₁₀IU/ml）^a	4.47（4.30～4.65）	4.45（4.21～4.53）	Z = 0.634	0.526
?	HBeAg（S/CO）^a	1 406.84（1 154.18～1 541.37）	1 389.92（1 209.01～1 539.06）	Z=－0.056	0.955
?	HBV DNA（log₁₀IU/ml）^a	8.09（7.55～8.23）	7.89（7.57～8.23）	Z= 0.544	0.586
孕期ALT水平升高[例（%）]		0（0.00）	12（26.67）	χ²= 13.846	<0.001^b
停药时水平		?	?	?	?
?	HBsAg（log₁₀IU/ml）^a	4.46（4.27～4.62）	4.45（3.84～4.54）	Z= 0.661	0.509
?	HBeAg（S/CO）^a	1 314（1 112.74～1 506.59）	1 305.18（1 020.89～1 112.74）	Z=－0.524	0.605
?	HBV DNA（log₁₀IU/ml）^a	3.91（3.37～4.45）	4.21（3.41～4.80）	Z= 1.123	0.261

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