Ochsner Medical Center, New Orleans, Louisiana, USA.
Cedar Sinai Medical Center, Los Angeles, California, USA.
Am J Gastroenterol. 2019 Aug;114(8):1283-1291. doi: 10.14309/ajg.0000000000000221.
Alterations in the immune system can result in alanine aminotransferase (ALT) flares either during pregnancy or after delivery in women with chronic hepatitis B virus (HBV) infection. The aim of this study was to prospectively assess changes in serum biochemical and virological markers of HBV infection during and after pregnancy in a large North American cohort of pregnant women with chronic HBV.
Adult pregnant women enrolled in the Hepatitis B Research Network between 2011 and 2016 were included. Serum ALT values and HBV DNA viral levels were obtained at <28 weeks and >28 weeks of gestation and <16 weeks, 16-31 weeks, and 32-48 weeks postpartum. Outcomes of ALT flares included severity, duration, and initiation of antiviral therapy.
Among the 158 pregnant women with chronic HBV, the median age was 33 years, 73% were Asian, and 63% were hepatitis B e antigen (HBeAg) negative. The median HBV DNA level was substantially higher in the HBeAg-positive vs HBeAg-negative women (1.3 × 10 vs 343 IU/mL), but serum ALT levels at their first study visit were similar. Among untreated pregnant women, there was a very mild increase in serum ALT postpartum among both HBeAg-positive and HBeAg-negative women (P < 0.001). Serum ALT flares (range 107-513 U/L) developed in 3.4% (5/149) during pregnancy and in 4.3% (4/92) after delivery. Twenty-two percent were initiated on antiviral therapy. After withdrawal of prophylactic anti-HBV therapy, 17.2% (5/29) developed serum ALT flares (range 107-208 U/L) within 14 weeks of drug discontinuation, and 3 additional women had flares despite continuous anti-HBV therapy during pregnancy or postpartum. Many ALT flares were not associated with significant changes in HBV DNA levels. No flares were severe with elevations of bilirubin or clinical decompensation.
Spontaneous ALT flares in untreated pregnant women with chronic HBV are infrequent, mild, and self-limited both prepartum and postpartum. Although flares after the withdrawal of antiviral therapy postpartum are more common, they were also mild and self-limited. Further studies of the immunopathogenesis of pregnancy-related flares are needed, as well as effects on long-term outcome of the mother and infant.
在慢性乙型肝炎病毒（HBV）感染的女性中，妊娠期间或产后，免疫系统的改变可导致丙氨酸氨基转移酶（ALT）升高。本研究旨在前瞻性评估 158 例慢性 HBV 感染的北美大型孕妇队列在妊娠期间和产后的血清生化和 HBV 感染病毒学标志物的变化。
纳入 2011 年至 2016 年期间入组乙型肝炎研究网络的成年孕妇。在妊娠 <28 周和 >28 周以及产后 <16 周、16-31 周和 32-48 周时，获取血清 ALT 值和 HBV DNA 病毒载量。ALT 升高的结局包括严重程度、持续时间和抗病毒治疗的启动。
在 158 例慢性 HBV 孕妇中，中位年龄为 33 岁，73%为亚洲人，63%为乙型肝炎 e 抗原（HBeAg）阴性。HBeAg 阳性与 HBeAg 阴性女性的 HBV DNA 水平中位数明显更高（1.3×10 与 343 IU/mL），但首次就诊时的血清 ALT 水平相似。在未经治疗的孕妇中，HBeAg 阳性和 HBeAg 阴性女性的产后血清 ALT 均有轻度升高（P < 0.001）。3.4%（5/149）的孕妇在妊娠期间和 4.3%（4/92）的孕妇在产后发生血清 ALT 升高（范围 107-513 U/L）。22%开始接受抗病毒治疗。在停止预防性抗 HBV 治疗后，17.2%（5/29）在停药后 14 周内出现血清 ALT 升高（范围 107-208 U/L），尽管在妊娠或产后期间持续接受抗 HBV 治疗，仍有 3 名女性出现了升高。许多 ALT 升高与 HBV DNA 水平的显著变化无关。无严重升高胆红素或临床失代偿的情况。
未经治疗的慢性 HBV 感染孕妇的自发性 ALT 升高在产前和产后均不常见、轻度且自限性。尽管产后停止抗病毒治疗后的升高更为常见，但它们也是轻度且自限性的。需要进一步研究妊娠相关升高的免疫发病机制，以及对母婴长期结局的影响。
