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
ARTICLE HIGHLIGHTS
Research background

Intrahepatic cholestasis of pregnancy (ICP) is a rare but severe hepatic complication for both mother and unborn child. Diagnosis is normally based on elevated serum levels of bile acids. Unfortunately, these blood tests usually take several hours, even at maximum care facilities. So far, there are no screening test for liver disease in pregnancy besides serological testing for viral hepatitis in the third trimester.

Research motivation

Measurement of liver stiffness (LS) through elastographic techniques has become the novel gold standard for the non-invasive diagnosis of liver cirrhosis often avoiding invasive liver biopsies. LS is not only highly correlated to the hepatic fibrosis stage but can also be elevated due to other important confounding factors such as inflammation, congestion or cholestasis. For these reasons, liver elastography could be an ideal diagnostic tool to address hepatic complications during pregnancy.

Research objectives

The aim of the present study was to specifically explore LS in a large cohort of women with ICP before and after delivery compared to a control group with uncomplicated pregnancy.

Research methods

LS and the hepatic steatosis marker controlled attenuation parameter (CAP) were measured in 100 pregnant women with ICP using transient elastography (Fibroscan, Echosens, Paris, France). In 17 cases, LS could be measured after delivery. A large cohort of women with uncomplicated pregnancy served as control group. Routine laboratory, levels of bile acids and the apoptosis marker M30 were also measured.

Research results

In the third trimester, women with ICP show a significantly increased LS at 7.3 ± 3.0 kPa compared to controls (6.2 ± 2.3 kPa, P < 0.0001). LS decreases significantly 24 h after deliver and remains higher in ICP (5.8 ± 1.7 kPa vs 4.2 ± 0.9 kPa, P < 0.0001). In ICP, LS is mainly correlated with levels of bile acids and the apoptosis marker M30. No correlation was seen with GGT and GGT even increased after delivery in women with ICP.

Research conclusions

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.

Research perspectives

In the future, elastography should be further validated in order to early identify women at risk for complications. Moreover, elastography studies should be combined with genetic risk assessment, as several mutations of bile transport proteins are involved in the development of ICP.