修回日期: 2020-07-02
接受日期: 2020-07-15
在线出版日期: 2020-08-28
妊娠期间母体肝脏血供减少, 负荷代谢增加等容易使妊娠期肝炎发作, 严重者将出现肝衰竭, 导致凝血机制异常, 引起大量出血和感染, 胎儿宫内窘迫, 早产, 死胎等. 因此, 对慢性乙型肝炎病毒(hepatitis B virus, HBV)感染孕妇治疗和管理的高度重视是降低HBV母婴传播的关键所在, 也是临床医护人员关注的重要问题, 尤其关注妊娠期肝炎发作的早期诊断和治疗尤为重要.
观察慢性HBV感染孕妇妊娠期肝炎发作的临床特点及抗病毒治疗的疗效评价.
选择2017-02/2019-06在浙江省余姚市妇幼保健院就诊的慢性HBV感染孕妇180例为研究对象, 在妊娠期每4-12 wk行肝功能, HBV血清标志物检查以判断是否有妊娠期肝炎发作. 对于明确诊断者即可给予口服替比夫定600 mg, 1次/d. 观察慢性HBV感染孕妇妊娠期肝炎发作临床特点和丙氨酸转氨酶(alanine aminotransferase, ALT), HBV血清标志物和HBV DNA的变化, 以及妊娠不同时间点抗病毒治疗后ALT复常率, HBV DNA和乙型肝炎核心抗原(hepatitis B e antigen, HBeAg)阴转率及HBeAg 血清学转换率.
本研究纳入180例慢性HBV感染孕妇, 其中48例(26.67%)孕妇妊娠期肝炎发作. 年龄26-36岁, 平均32.3岁±2.4岁; 肝炎发作时间6-34 wk, 平均20.3 wk±7.8 wk；ALT平均值为224.95 U/L±19.6 U/L. 与妊娠期无肝炎发作孕妇比较, 妊娠期肝炎发作孕妇ALT, HBV DNA变化显著(P<0.05), 乙型肝炎表面抗原和HBeAg定量均明显降低(P<0.05). 妊娠期肝炎发作孕妇随着治疗时间的延长ALT复常率, HBV DNA阴转率, HBeAg阴转率及HBeAg血清学转换率均有不同程度的升高, 尤其在治疗36 wk时, 孕妇ALT复常率为100.0%, HBV DNA阴转率为72.92%, HBeAg阴转率为41.67%, HBeAg血清学转换率为37.5%, 均明显高于治疗6 wk时、治疗12 wk时和治疗24 wk的疗效, 差异比较均有统计学意义(P<0.05).
慢性HBV感染孕妇妊娠期肝炎发作多发生在妊娠中期, 给予积极抗病毒治疗后在第36周时HBeAg血清学转换率高.
核心提要: 关注妊娠期肝炎发作的早期诊断和治疗是临床医务人员关注的重要问题, 早期诊断并采取抗病毒治疗, 既可恢复孕妇肝功, 又可防止肝衰竭, 保证胎儿足月妊娠和降低其他并发症发生, 保证母婴安全.
引文著录: 杜鹃, 郑维平, 冯银宏. 慢性乙型肝炎病毒感染孕妇妊娠期肝炎发作的临床特点及抗病毒治疗的疗效评价. 世界华人消化杂志 2020; 28(16): 813-818
Revised: July 2, 2020
Accepted: July 15, 2020
Published online: August 28, 2020
During pregnancy, decreased maternal liver blood supply and increased load metabolism make woman susceptible to hepatitis attack. Severe cases often develop liver failure, leading to coagulation mechanism abnormality, bleeding and infection, fetal distress, premature delivery, stillbirth, etc. Therefore, high attention to the treatment and management of pregnant women with chronic hepatitis B virus (HBV) infection is the key to reducing the mother-to-child transmission of HBV, representing an important issue of concern for clinical medical personnel. Therefore, the early diagnosis and treatment of hepatitis attack during pregnancy are particularly important.
To observe the clinical characteristics of HBV in pregnant women and evaluate the efficacy of antiviral therapy.
A total of 180 pregnant women with chronic HBV infection who visited Yuyao Maternal and Child Health Center of Zhejiang Province from February 2017 to June 2019 were selected as study subjects. Liver function was tested every 4 to 12 wk during pregnancy, and HBV serum markers were checked to determine whether there was hepatitis attack during pregnancy. For those with a definite diagnosis, tibivudine was given orally at a dose of 600 mg once per day. The clinical characteristics, alanine aminotransferase (ALT), HBV serum markers, and HBV DNA changes in pregnant women with chronic HBV infection were recorded. ALT recovery rate, HBV DNA and hepatitis B e antigen (HBeAg) negative conversion rate, and HBeAg seroconversion rate after antiviral treatment at different time points during pregnancy were also recorded.
Of the 180 pregnant women with chronic HBV infection included in this study, 48 (26.67%) had hepatitis attacks during pregnancy. The average age was 32.3 ± 2.4 years. The duration of hepatitis attacks ranged from 6 to 34 wk, with an average of 20.3 ± 7.8 wk. The mean value of ALT was 224.95 ± 19.6 U/L. Compared with pregnant women without hepatitis attack during pregnancy, ALT and HBV DNA changes were significant (P < 0.05), and hepatitis B surface antigen and HBeAg quantification were significantly reduced (P < 0.05). For hepatitis attacks during pregnancy, with the extension of treatment time, ALT recovery rate, HBV DNA negative conversion rate, HBeAg negative conversion rate, and HBeAg seroconversion rate had varying degrees of rise. Especially at 36 wk after treatment, the ALT recovery rate was 100.0%, HBV DNA negative conversion rate was 72.92%, HBeAg negative conversion rate was 41.67%, and HBeAg seroconversion rate was 37.5%, which were significantly higher than those at 6 wk, 12 wk, and 24 wk of treatment (P < 0.05).
Hepatitis attacks in pregnant women with chronic HBV infection usually occur in the second trimester.
- Citation: Du J, Zheng WP, Feng YH. Clinical characteristics and efficacy evaluation of antiviral therapy in pregnant women with chronic hepatitis B virus infection. Shijie Huaren Xiaohua Zazhi 2020; 28(16): 813-818
- URL: https://www.wjgnet.com/1009-3079/full/v28/i16/813.htm
- DOI: https://dx.doi.org/10.11569/wcjd.v28.i16.813
我国乙型肝炎病毒(hepatitis B virus, HBV)传播的主要途径是通过母婴传播, 当慢性HBV感染时, 大多数孕妇均处于免疫耐受期[1,2]. 由于肝脏是代谢旺盛的器官, 妊娠期间母体肝脏血供减少, 负荷代谢增加等容易使妊娠期肝炎发作, 严重者将出现肝衰竭, 导致凝血机制异常, 引起大量出血和感染, 胎儿宫内窘迫, 早产, 死胎等[3,4]. 因此, 对慢性HBV感染孕妇治疗和管理的高度重视是降低HBV母婴传播的关键所在, 也是临床医护人员关注的重要问题, 尤其关注妊娠期肝炎发作的早期诊断和治疗尤为重要. 早期明确诊断并采取抗病毒治疗, 既可恢复孕妇肝功, 又可防止肝衰竭, 保证胎儿足月妊娠和降低其他并发症发生, 保证母婴安全[5-7]. 因此, 本研究对180例慢性HBV感染孕妇为研究对象研究其妊娠期间肝炎发作情况和在不同妊娠时间抗病毒药物治疗的临床疗效.
1.1.1 一般资料: 选择2017-02/2019-06在浙江省余姚市妇幼保健院就诊的慢性HBV感染孕妇180例为研究对象, 年龄26-38岁, 平均32.1岁±3.2岁.
1.1.2 纳入标准: (1)慢性HBV感染者, 乙型肝炎表面抗原(hepatitis B surface antigen, HBsAg), 乙型肝炎核心抗原(hepatitis B e antigen, HBeAg)和HBV DNA阳性; (2)妊娠≥4 wk; (3)经患者及家属知情同意; (4)经医院伦理委员会批准同意者.
1.1.3 排除标准: (1)急性HBV感染者; (2)HBV合并人类免疫缺陷病毒(human immunodeficiency virus, HIV), 丙肝病毒等其它噬肝病毒感染者; (3)HIV感染者; (4)近1 mo内因其他疾病用过激素或细胞毒药物者; (5)同时参与其他研究者; (6)依从性差者, 或中途退出者.
1.2.1 研究方法: 在妊娠期每4-12 wk行肝功能, HBV血清标志物检查以判断是否有妊娠期肝炎发作. 对于明确诊断者即可给予口服替比夫定600 mg, 1次/d, 并观察妊娠不同时间点疗效.
1.2.2 观察指标: 观察慢性HBV感染孕妇妊娠期肝炎发作临床特点和ALT, HBV血清标志物和HBV DNA的变化, 以及妊娠不同时间点抗病毒治疗后ALT复常率, HBV DNA和HBeAg阴转率及HBeAg 血清学转换率.
统计学处理 采用SPSS 23.0软件分析数据. 计数资料采用(%)表示, 采用χ2检验; 计量资料以mean±SD表示, 采用t检验. P<0.05为差异有统计学意义.
本研究纳入180例慢性HBV感染孕妇, 其中48例(26.67%)孕妇妊娠期肝炎发作. 年龄26-36岁, 平均32.3岁±2.4岁; 肝炎发作时间6-34 wk, 平均20.3 wk±7.8 wk; ALT平均值为224.95 U/L±19.6 U/L. 见表1.
| 项目 | 肝炎发作孕妇(n = 48) | 平均 |
| 年龄(岁) | ||
| 26-30 | 27 (56.25) | 27.83±1.24 |
| 31-36 | 21 (43.75) | 33.21±1.62 |
| 肝炎发作时间(wk) | ||
| <12 | 2 (4.17) | 9.15±1.61 |
| 13-24 | 41 (85.42) | 19.34±2.12 |
| 25-36 | 5 (10.42) | 28.47±1.91 |
| ALT峰值(U/L)×正常值 | ||
| 2-5 | 28 (58.33) | 3.65±1.20 |
| 5-10 | 14 (29.17) | 7.12±1.63 |
| >10 | 6 (12.5) | 12.48±0.82 |
| HBV DNA(Log10 IU/mL) | ||
| <6 | 10 (20.83) | 4.96±0.53 |
| 6-7 | 7 (14.58) | 6.43±0.32 |
| >7 | 31 (64.59) | 8.16±1.23 |
| HBsAg(Log10 IU/mL) | ||
| <4 | 25 (52.08) | 3.81±0.32 |
| 4-5 | 22 (45.83) | 4.45±0.23 |
| >5 | 1 (2.09) | 5.27±0.22 |
| HBeAg(Log10 S/CO) | ||
| <2 | 7 (14.58) | 1.76±0.31 |
| 2-3 | 24 (50.0) | 2.58±0.32 |
| >3 | 17 (35.42) | 3.26±0.24 |
与妊娠期无肝炎发作孕妇比较, ALT, HBV DNA变化显著(P<0.05), HBsAg和HBeAg定量均明显降低(P<0.05). 见表2.
| 组别 | n | ALT (IU/mL) | HBV DNA (Log10 IU/mL) | HBsAg (Log10 IU/mL) | HBeAg (Log10 S/CO) |
| 肝炎发作组 | 48 | 43.67±7.28 | 12.23±3.25 | 4.02±0.56 | 2.69±0.57 |
| 无肝炎发作组 | 132 | 34.58±4.34 | 7.18±1.82 | 4.39±0.48 | 2.93±0.62 |
| t值 | -0.482 | 0.823 | -3.256 | -2.246 | |
| P值 | 0.007 | 0.001 | 0.001 | 0.025 |
妊娠期肝炎发作孕妇随着治疗时间的延长ALT复常率, HBV DNA阴转率, HBe Ag阴转率及HBeAg血清学转换率均有不同程度的升高, 尤其在治疗36 wk时, 孕妇ALT复常率为100.0%, HBV DNA阴转率为72.92%, HBeAg阴转率为41.67%, HBeAg血清学转换率为37.5%, 均明显高于治疗6 wk时、治疗12 wk时和治疗24 wk的疗效, 差异均有统计学意义(P<0.05). 见表3.
既往有研究表明[8,9], 慢性HBV感染孕妇分娩后容易肝炎发作, 大多数在产后3 mo内发生, 发病率约为20%-35%, 这可能与分娩后孕妇免疫系统重建和内分泌水平改变有很大关系. 但是, 目前临床上关于孕妇妊娠期肝炎发作研究较少. 因此, 本研究对180例慢性HBV感染孕妇妊娠期内肝炎发作情况及抗病毒治疗效果进行研究, 旨在为临床诊疗提供参考价值.
本研究纳入180例慢性HBV感染孕妇, 其中48例(26.67%)孕妇妊娠期肝炎发作; 年龄26-36岁, 平均32.3岁±2.4岁, 其中以30岁以下多见, 约占56.25%; 肝炎发作时间6-34 wk, 平均20.3wk±7.8 wk, 其中在13-24 wk妊娠中期多见, 共41例(85.42%). 本研究孕妇ALT平均值为224.95 U/L±19.6U/L, 其中58.33% ALT轻中度升高, 有12.5%的ALT显著升高, 但未发生肝衰竭, 所以在临床上对妊娠期慢性HBV感染孕妇肝功能密切监测非常重要, 对于肝功能损害严重者及时给予抗病毒药物治疗, 在一定程度上会保护肝脏, 防止病情加重, 出现爆发性肝衰竭[10,11]. 本研究孕妇的HBV DNA病毒复制活跃, 其中31例孕妇(64.59%)的HBV DNA>7 Log10 IU/mL. 但孕妇HBV DNA和HBsAg水平并不一致, HBsAg有明显的降低, 这可能与本研究样本量小有关系, 也可能与病毒变异有关, 在今后的研究中将进一步增加样本量以明确其原因.
本研究对慢性HBV感染孕妇肝炎发作和无肝炎发作孕妇的ALT, HBV DNA, HBsAg和HBeAg定量进行对比分析, 发现妊娠期肝炎发作孕妇的HBsAg和HBeAg定量低(P<0.05), ALT, HBV DNA变化显著(P<0.05). 所以在临床上可通过HBsAg和HBeAg定量进行预测慢性HBV感染孕妇是否肝炎发作, 但仅做参考. 在今后的研究中将进一步通过logistic回归分析对影响孕妇肝炎发作的多因素分析, 以提高对孕妇肝炎发作的独立危险因子准确预测.
既往有研究表明[12,13], 慢性HBV感染孕妇采用不同抗病毒药物治疗后HBV DNA阴转率, HBeAg血清阴转率, HBeAg血清学转换率均有不同程度的提高, 但疗效不一. 本研究给予口服替比夫定治疗, 结果表明, 在治疗36 wk时, 孕妇ALT复常率为100.0%, HBV DNA阴转率为72.92%, HBeAg阴转率为41.67%, HBeAg血清学转换率为37.5% (P<0.05). 由此可见, 妊娠期肝炎发作孕妇抗病毒治疗短期效果好. 本研究治疗36 wk, 是否延长治疗时间能达到最佳效果有待进一步研究, 在今后的研究中将延长治疗时间, 并对分娩后继续抗病毒治疗以观察HBsAg定量变化, 从而为临床治疗提供客观依据[14,15].
综上所述, 慢性HBV感染孕妇在妊娠期应定期监测肝功能, HBV血清标志物和HBV DNA, 尤其在妊娠中期, 观察是否出现肝炎发作, 并积极给予抗病毒药物治疗, 以提高HBeAg血清学转换率.
对慢性乙型肝炎病毒(hepatitis B virus, HBV)感染孕妇治疗和管理的高度重视是降低HBV母婴传播的关键所在, 也是临床医护人员关注的重要问题, 尤其关注妊娠期肝炎发作的早期诊断和治疗尤为重要.
观察HBV感染孕妇妊娠期肝炎发作的临床特点.
观察HBV感染孕妇妊娠期肝炎发作的临床特点及抗病毒治疗的疗效评价.
选择慢性HBV感染孕妇180例为研究对象, 在妊娠期每4-12 wk行肝功能, HBV血清标志物检查以判断是否有妊娠期肝炎发作. 观察慢性HBV感染孕妇妊娠期肝炎发作临床特点和丙氨酸转氨酶(alanine aminotransferase, ALT), HBV血清标志物和HBV DNA的变化, 以及妊娠不同时间点抗病毒治疗后ALT复常率, HBV DNA和乙型肝炎核心抗原(hepatitis B e antigen, HBeAg)阴转率及HBeAg 血清学转换率.
与妊娠期无肝炎发作孕妇比较, 妊娠期肝炎发作孕妇ALT, HBV DNA变化显著(P<0.05), 乙型肝炎表面抗原和HBeAg定量均明显降低(P<0.05). 妊娠期肝炎发作孕妇随着治疗时间的延长ALT复常率, HBV DNA阴转率, HBe Ag阴转率及HBeAg血清学转换率均有不同程度的升高, 尤其在治疗36 wk时, 孕妇ALT复常率为100.0%, HBV DNA阴转率为72.92%, HBeAg阴转率为41.67%, HBeAg血清学转换率为37.5%, 均明显升高(P<0.05).
慢性HBV感染孕妇妊娠期肝炎发作多发生在妊娠中期, 给予积极抗病毒治疗后在第36周时HBeAg血清学转换率高.
关注妊娠期肝炎发作的早期诊断和治疗是临床医务人员关注的重要问题.
学科分类: 胃肠病学和肝病学
手稿来源地: 浙江省
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