Nees Juliane, Ammon Franziska J, Mueller Johannes, Fluhr Herbert, Mueller Sebastian
Department of Gynecology and Obstetrics, University Hospital Heidelberg, Heidelberg 69120, Germany.
Center for Alcohol Research, University Hospital Heidelberg, Heidelberg 69120, Germany.
World J Hepatol. 2023 Jul 27;15(7):904-913. doi: 10.4254/wjh.v15.i7.904.
Intrahepatic cholestasis of pregnancy (ICP) is a rare but severe complication for both the mother and the unborn child. The diagnosis is primarily based on elevated serum levels of bile acids. In a large ICP cohort, we here study in detail liver stiffness (LS) using transient elastography (TE), now widely used to non-invasively screen for liver cirrhosis within minutes.
To specifically explore LS in a large cohort of women with ICP compared to a control group with uncomplicated pregnancy.
LS and hepatic steatosis marker controlled attenuation parameter (CAP) were measured in 100 pregnant women with ICP using TE (Fibroscan, Echosens, Paris, France) between 2010 and 2020. In 17 cases, LS could be measured postpartum. 450 women before and 38 women after delivery with uncomplicated pregnancy served as control group. Routine laboratory, levels of bile acids and apoptosis marker caspase-cleaved cytokeratin 18 fragment (M30) were also measured.
Women with ICP had significantly elevated transaminases but normal gamma-glutamyl transferase (GGT). Mean LS was significantly increased at 7.3 ± 3.0 kPa compared to the control group at 6.2 ± 2.3 kPa ( < 0.0001). Postpartum LS decreased significantly in both groups but was still higher in ICP (5.8 ± 1.7 kPa 4.2 ± 0.9 kPa, < 0.0001), respectively. In ICP, LS was highly significantly correlated with levels of bile acids and M30 but not transaminases. No correlation was seen with GGT that even increased significantly after delivery in the ICP group. Bile acids were mostly correlated with the liver apoptosis marker M30, LS and levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin. In multivariate analysis, LS remained the sole parameter that was independently associated with elevated bile acids.
In conclusion, LS is significantly elevated in ICP which is most likely due to toxic bile acid accumulation and hepatocyte apoptosis. In association with conventional laboratory markers, LS provides additional non-invasive information to rapidly identify women at risk for ICP.
妊娠期肝内胆汁淤积症(ICP)是一种罕见但对母亲和胎儿都很严重的并发症。诊断主要基于血清胆汁酸水平升高。在一个大型ICP队列中,我们在此使用瞬时弹性成像(TE)详细研究肝脏硬度(LS),TE现在被广泛用于在几分钟内非侵入性筛查肝硬化。
在一大群ICP女性中与无并发症妊娠的对照组相比,专门探究LS。
在2010年至2020年间,使用TE(Fibroscan,Echosens,法国巴黎)对100例ICP孕妇测量LS和肝脏脂肪变性标志物受控衰减参数(CAP)。17例患者产后可测量LS。450例未合并并发症妊娠的产前女性和38例产后女性作为对照组。还测量了常规实验室指标、胆汁酸水平和凋亡标志物半胱天冬酶切割的细胞角蛋白18片段(M30)。
ICP女性转氨酶显著升高,但γ-谷氨酰转移酶(GGT)正常。平均LS显著升高,为7.3±3.0 kPa,而对照组为6.2±2.3 kPa(<0.0001)。两组产后LS均显著下降,但ICP组仍较高(分别为5.8±1.7 kPa对4.2±0.9 kPa,<0.0001)。在ICP中,LS与胆汁酸和M30水平高度显著相关,但与转氨酶无关。与GGT无相关性,甚至在ICP组产后GGT显著升高。胆汁酸大多与肝脏凋亡标志物M30、LS以及丙氨酸转氨酶、天冬氨酸转氨酶和胆红素水平相关。在多变量分析中,LS仍然是与胆汁酸升高独立相关的唯一参数。
总之,ICP中LS显著升高,这很可能是由于有毒胆汁酸积累和肝细胞凋亡所致。与传统实验室标志物相结合,LS提供了额外的非侵入性信息,以快速识别有ICP风险的女性。