Maternal serum Sortilin-1 level as a potential biomarker for intrahepatic cholestasis of pregnancy

Abstract

Objective: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease related to pregnancy in women. Sortilin-1 is a sorting receptor belonging to the vacuolar protein sorting 10 (Vps10p) domain family, and recent studies have shown that Sortilin-1 has a distinct role in the pathogenesis of biliary fibrosis and cirrhosis. We aimed to evaluate maternal serum Sortilin-1 level as a potential biomarker in pregnant women with intrahepatic cholestasis.

Materials and methods: A prospective observational cohort study was conducted. We enrolled 80 pregnant women, 49 with the diagnosis of intrahepatic cholestasis of pregnancy and 31 healthy controls. Then, we measured maternal serum Sortilin-1 levels using an enzyme-linked immunosorbent assay method and compared them between groups.

Results: The mean Sortilin-1 level in the ICP group was higher than control group (3.3 ± 1.7 ng/mL vs. 2.0 ± 0.6 ng/mL, respectively, p < .001). The receiver operating characteristic curve (ROC) analysis based on maternal serum Sortilin-1 levels to predict the presence of ICP was 85.3% controls [area under the curve (AUC), 0.853; 95% CI, 0.738–0.938, p < .001]. The optimal cutoff value of Sortilin-1 was 2.24 ng/mL (71.4% sensitivity and 74.2% specificity) to detect intrahepatic cholestasis of pregnancy.

Conclusion: Elevated maternal serum Sortilin-1 levels are associated with ICP and can be used as a disease biomarker. Sortilin-1 levels can be combined with total bile acids, transaminases, and blood coagulation profile in the follow-up of ICP.

摘要

目的

妊娠期肝内胆汁淤积症（ICP）是女性最常见的妊娠相关肝病。Sortilin-1是属于空泡蛋白分选10（Vps10p）结构域家族的一种分选受体, 最近的研究表明Sortilin-1在胆道纤维化和肝硬变的发病机制中具有明显的作用。我们的目的是评估母体血清Sortilin-1水平作为妊娠期肝内胆汁淤积症孕妇的潜在生物标记物。

材料与方法

进行了前瞻性观察队列研究。我们招募了80名孕妇, 49名诊断为妊娠期肝内胆汁淤积症和31名健康对照。然后, 我们采用酶联免疫吸附分析法检测母体血清Sortilin-1水平, 并进行组间比较。

结果

ICP组患者血清Sortilin-1平均水平显著高于正常对照组（3.3 ± 1.7 ng/mL vs. 2.0 ± 0.6 ng/mL, p<.001）。基于母体血清Sortilin-1水平预测ICP存在的受试者工作特征曲线（ROC）分析为85.3%的对照组[曲线下面积（AUC）, 0.853；95%CI, 0.738-0.938, p<.001]。Sortilin-1检测ICP的最佳截断值为2.24 ng/ml（敏感性为71.4%, 特异性为74.2%）。

结论

孕妇血清中Sortilin-1水平升高与ICP有关, 可作为疾病的生物标志物。Sortilin-1水平可与总胆汁酸、转氨酶和凝血谱联合用于ICP的随访。

关键词:

• 妊娠期肝内胆汁淤积症
• Sortilin-1
• 生物标志物
• 妊娠
• 胆汁酸

Keywords:

• Intrahepatic cholestasis of pregnancy
• Sortilin-1
• biomarker
• pregnancy
• bile acids

Acknowledgements

Fazilet Ertas and İsmail İzzettin Ertas.

Authorship contributions

Concept: SE, Design: SE, U.T., Data Collection or Processing: G.U., Z.G.O, S.Y., I.D., Analysis or Interpretation: U.T. and SE, Literature Search: SE, G.U., Writing: SE.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Ethics committee approval

The study was approved by the Local Ethics Committee with the approval number of SBÜSEAH-KAEK-2019/4/25 in accordance with the 2003 Helsinki Declaration.

Informed consent

Written informed consent for the study was obtained from all patients according to the principles outlined by the Declaration of Helsinki (2013).

Trial registration number

SBÜSEAH-KAEK-2019/4/25