Observational Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2018; 24(38): 4393-4402
Published online Oct 14, 2018. doi: 10.3748/wjg.v24.i38.4393
Liver stiffness reversibly increases during pregnancy and independently predicts preeclampsia
Franziska J Ammon, Anna Kohlhaas, Omar Elshaarawy, Johannes Mueller, Thomas Bruckner, Christof Sohn, Gabriele Fluhr, Herbert Fluhr, Sebastian Mueller
Franziska J Ammon, Christof Sohn, Herbert Fluhr, Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg 69120, Germany
Anna Kohlhaas, Omar Elshaarawy, Johannes Mueller, Gabriele Fluhr, Sebastian Mueller, Department of Medicine and Center for Alcohol Research, Liver Disease and Nutrition, Salem Medical Center, University of Heidelberg, Heidelberg 69121, Germany
Thomas Bruckner, Institute of Medical Biometry und Informatics, University of Heidelberg, Heidelberg 69121, Germany
Author contributions: Fluhr H and Mueller S designed research; Ammon FJ, Kohlhaas A and Fluhr G performed measurements; Ammon FJ, Mueller J and Mueller S analyzed the data and wrote the paper; Elshaarawy O revised the paper; Bruckner T reviewed statistics; Elshaarawy O, Sohn C and Fluhr H reviewed the paper.
Supported by the Dietmar Hopp Foundation (in part, DFG), No. MU 1373/9-1.
Institutional review board statement: The study was approved by the Ethical Committee of the University of Heidelberg.
Informed consent statement: All participants of the study, or their legal guardians, provided written informed consent prior to study enrollment.
Conflict-of-interest statement: The authors have declared no conflicts of interest.
Data sharing statement: Dataset and other information are available from the corresponding author at sebastian.mueller@urz.uni-heidelberg.de. Patients gave informed consent before inclusion in the study; the presented data are anonymized and the risk of identification is very low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Sebastian Mueller, MD, PhD, Professor, Department of Internal Medicine, Salem Medical Center and Center for Alcohol Research and Liver Disease, University of Heidelberg, Zeppelinstraße 11-33, Heidelberg 69121, Germany. sebastian.mueller@urz.uni-heidelberg.de
Telephone: +49-6221-483210 Fax: +49-6221-484494
Received: August 1, 2018
Peer-review started: August 1, 2018
First decision: August 24, 2018
Revised: September 20, 2018
Accepted: October 5, 2018
Article in press: October 5, 2018
Published online: October 14, 2018

To study liver stiffness (LS) during pregnancy and its association with complications during pregnancy.


In this observational, diagnostic study, 537 pregnant women were prospectively enrolled at the Department of Obstetrics and Gynecology, University hospital Heidelberg and Salem Medical Center. LS was measured using the Fibroscan device (Echosens, Paris) in all women and in 41 cases 24 h after delivery. Clinical and morphological data were recorded and abdominal ultrasound and standard laboratory tests were performed. No complications were observed in 475 women (controls) while preeclampsia and intrahepatic cholestasis of pregnancy (ICP) developed in 22 and 40 women, respectively.


In controls, LS increased significantly from initially 4.5 ± 1.2 kPa in the second trimester to 6.0 ± 2.3 kPa (P < 0.001) in the third trimester. In the third trimester, 41% of women had a LS higher than 6 kPa. Elevated LS in controls was significantly correlated with alkaline phosphatase, leukocytes, gestational age and an increase in body weight and body mass index (BMI). In women with pregnancy complications, LS was significantly higher as compared to controls (P < 0.0001). Moreover, in multivariate analysis, LS was an independent predictor for preeclampsia with an odds ratio of 2.05 (1.27-3.31) and a cut-off value of 7.6 kPa. In contrast, ICP could not be predicted by LS. Finally, LS rapidly decreased in all women within 24 h after delivery from 7.2 ± 3.3 kPa down to 4.9 ± 2.2 kPa (P < 0.001).


During pregnancy, LS significantly and reversibly increases in the final trimester of pregnant women without complications. In women with preeclampsia, LS is significantly elevated and an independent non-invasive predictor.

Keywords: Pregnancy, Transient elastography, Liver stiffness, Pregnancy complications, Hemolysis, elevated liver enzymes and low platelets syndrome, Intrahepatic cholestasis of pregnancy, Preeclampsia

Core tip: Liver stiffness (LS) was measured by transient elastography during pregnancy in 537 healthy pregnant women without complications and in 62 women with pregnancy complications such as preeclampsia or intrahepatic cholestasis of pregnancy. Our results show that LS increases during pregnancy to levels above 6 kPa even in women without pregnancy complications and rapidly normalizes within 24 h after delivery. LS was significantly elevated in women with preeclampsia and, moreover, an independent predictor for preeclampsia in multivariate analysis. In conclusion, LS could be a novel non-invasive screening parameter to identify pregnant women at risk for complications of pregnancy.