Case Control Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jul 27, 2023; 15(7): 904-913
Published online Jul 27, 2023. doi: 10.4254/wjh.v15.i7.904
Liver stiffness in pregnant women with intrahepatic cholestasis of pregnancy: A case control study
Juliane Nees, Franziska J Ammon, Johannes Mueller, Herbert Fluhr, Sebastian Mueller
Juliane Nees, Franziska J Ammon, Department of Gynecology and Obstetrics, University Hospital Heidelberg, Heidelberg 69120, Germany
Johannes Mueller, Sebastian Mueller, Center for Alcohol Research, University Hospital Heidelberg, Heidelberg 69120, Germany
Herbert Fluhr, Division of Obstetrics, Department of Obstetrics and Gynecology, Medical University of Graz, Graz 8036, Austria
Author contributions: Nees J, Fluhr H, and Mueller S designed and coordinated the study; Nees J and Ammon FJ performed the experiments; Nees J, Mueller S, and Mueller J analyzed and interpreted the data; Nees J and Mueller S wrote the manuscript.
Supported by The Faculty of Medicine Heidelberg in The Form of The Rahel-Goitein-Strauss Fellowship to JN.
Institutional review board statement: The study was approved by the ethics committee of University of Heidelberg.
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Data available from the corresponding author at sebastian.mueller@urz.uni-heidelberg.de.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sebastian Mueller, PhD, Professor, Center for Alcohol Research, University Hospital Heidelberg, Im Neuenheimer Feld 350, Heidelberg 69120, Germany. sebastian.mueller@urz.uni-heidelberg.de
Received: March 27, 2023
Peer-review started: March 27, 2023
First decision: April 19, 2023
Revised: May 17, 2023
Accepted: June 12, 2023
Article in press: June 12, 2023
Published online: July 27, 2023
Processing time: 116 Days and 1 Hours
Abstract
BACKGROUND

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.

AIM

To specifically explore LS in a large cohort of women with ICP compared to a control group with uncomplicated pregnancy.

METHODS

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.

RESULTS

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 (P < 0.0001). Postpartum LS decreased significantly in both groups but was still higher in ICP (5.8 ± 1.7 kPa vs 4.2 ± 0.9 kPa, P < 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.

CONCLUSION

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.

Keywords: Intrahepatic cholestasis of pregnancy; Transient elastography; Bile acids; Liver stiffness; High risk pregnancy

Core Tip: Intrahepatic cholestasis of pregnancy (ICP) is a rare but severe complication in both mothers and unborn children. In a large ICP cohort, we studied liver stiffness (LS) in detail using transient elastography, which is now widely used for non-invasive screening of liver cirrhosis within minutes. LS is significantly elevated in pregnancies with ICP, most likely owing to toxic bile acid accumulation and hepatocyte apoptosis. Interestingly, no correlation was observed with γ-glutamyl transferase. In association with conventional laboratory markers, LS provides a novel non-invasive tool to rapidly identify women at risk for pregnancy complications.