Observational Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 27, 2022; 14(4): 778-790
Published online Apr 27, 2022. doi: 10.4254/wjh.v14.i4.778
Gravity assistance enables liver stiffness measurements to detect liver fibrosis under congestive circumstances
Takeshi Suda, Ai Sugimoto, Tsutomu Kanefuji, Atsushi Abe, Takeshi Yokoo, Takahiro Hoshi, Satoshi Abe, Shinichi Morita, Kazuyoshi Yagi, Masashi Takahashi, Shuji Terai
Takeshi Suda, Takahiro Hoshi, Satoshi Abe, Shinichi Morita, Kazuyoshi Yagi, Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami Uonuma 949-7302, Niigata, Japan
Ai Sugimoto, Masashi Takahashi, Division of Thoracic and Cardiovascular Surgery, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8122, Japan
Tsutomu Kanefuji, Department of Gastroenterology and Hepatology, Tsubame Rosai Hospital, Tsubame 959-1228, Niigata, Japan
Atsushi Abe, Department of Administration, Joetsu-Area General Health Care Center, Joetsu 943-0803, Niigata, Japan
Takeshi Yokoo, Department of Preemptive Medicine for Digestive Diseases and Healthy Active Life, Niigata University School of Medicine, Niigata 951-8122, Japan
Shuji Terai, Division of Gastroenterology and Hepatology, School of Medical and Dental Sciences, Niigata University, Niigata 951-8122, Japan
Author contributions: Suda T established the study concept, designed the research; Hoshi T, Abe S, Morita S and Takahashi M acquired the data; Suda T, Sugimoto A, Kanefuji T and Yokoo T analyzed and interpretated the data; Abe A supported the materials and performed statistical analyses; Suda T wrote the paper; Yagi K supervised the study; Abe A and Takahashi M critically revised the manuscript for important intellectual content; Terai S administratively supervised.
Institutional review board statement: In this study, two different cohorts were employed for liver stiffness measurements: cohort #1 (298 cases with various liver diseases) and cohort #2 (41 cases receiving cardiac surgery). The review boards of the Uonuma Institute of Community Medicine and Niigata University Medical and Dental Hospital approved both studies.
Informed consent statement: The review boards of Uonuma Institute of Community Medicine and Niigata University Medical and Dental Hospital did not require informed consent in the studies for cohorts #1 and #2 because these studies were retrospective studies using medical records and no additional invasive examinations were conducted for the study.
Conflict-of-interest statement: Takeshi Suda, Ai Sugimoto, Atsushi Abe, Tsutomu Kanefuji, Takahiro Hoshi, Satoshi Abe, Shinichi Morita, Takeshi Yokoo, Kazuyoshi Yagi, Masashi Takahashi, and Shuji Terai declare that they have no conflicts of interest. There is no relationship that should be disclosed in association with this study. The authors have nothing to disclose in relation to this manuscript.
Data sharing statement: The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.
STROBE statement: The guidelines of the STROBE Statement have been adopted.
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: Takeshi Suda, MD, PhD, Professor, Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, 4132 Urasa, Minami Uonuma 949-7302, Niigata, Japan. tspitt@med.niigata-u.ac.jp
Received: September 30, 2021
Peer-review started: September 30, 2021
First decision: December 4, 2021
Revised: December 30, 2021
Accepted: March 6, 2022
Article in press: March 6, 2022
Published online: April 27, 2022
Processing time: 204 Days and 5 Hours
Abstract
BACKGROUND

As survival has been prolonged owing to surgical and medical improvements, liver failure has become a prognostic determinant in patients with congestive heart diseases. Congestive hepatopathy, an abnormal state of the liver as a result of congestion, insidiously proceed toward end-stage liver disease without effective biomarkers evaluating pathological progression. Regular measurements of shear wave elastography cannot qualify liver fibrosis, which is a prognosticator in any type of chronic liver disease, in cases of congestion because congestion makes the liver stiff without fibrosis. We hypothesized that the effects of congestion and fibrosis on liver stiffness can be dissociated by inducing architectural deformation of the liver to expose structural rigidity.

AIM

To establish a strategy measuring liver stiffness as a reflection of architectural rigidity under congestion.

METHODS

Two-dimensional shear wave elastography (2dSWE) was measured in the supine (Sp) and left decubitus (Ld) positions in 298 consecutive cases as they were subjected to an ultrasound study for various liver diseases. Regions of interest were placed at twelve sites, and the median and robust coefficient of variation were calculated. Numerical data were compared using the Mann-Whitney U or Kruskal-Wallis test followed by Dunn's post-hoc multiple comparisons. The inferior vena cava (IVC) diameters at different body positions were compared using the Wilcoxon matched pairs signed rank test. The number of cases with cardiothoracic ratios greater than or not greater than 50% was compared using Fisher’s exact test. A correlation of 2dSWE between different body positions was evaluated by calculating Spearman correlation coefficients.

RESULTS

The IVC diameter was significantly reduced in Ld in subjects with higher 2dSWE values in Ld (LdSWE) than in Sp (SpSWE) (P = 0.007, (average ± SD) 13.9 ± 3.6 vs 13.1 ± 3.4 mm) but not in those with lower LdSWE values (P = 0.32, 13.3 ± 3.5 vs 13.0 ± 3.5 mm). In 81 subjects, SpSWE was increased or decreased in Ld beyond the magnitude of robust coefficient of variation, which suggests that body postural changes induced an alteration of liver stiffness significantly larger than the technical dispersion. Among these subjects, all 37 with normal SpSWE had a higher LdSWE than SpSWE (Normal-to-Hard, SpSWE - LdSWE (∆2dSWE): (minimum-maximum) -0.74 - -0.08 m/sec), whereas in 44 residual subjects with abnormal SpSWE, LdSWE was higher in 27 subjects (Hard-to-Hard, -0.74 - -0.05 m/sec) and lower in 17 subjects (Hard-to-Soft, 0.04 - 0.52 m/sec) than SpSWE. SpSWE was significantly correlated with ∆2dSWE only in Hard-to-Soft (P < 0.0001). ∆2dSWE was larger in each lobe than in the entire liver. When Hard-to-Hard and Hard-to-Soft values were examined for each lobe, fibrosis-4 or platelet counts were significantly higher or lower only for Hard-to-Soft vs Normal-to-Hard cases.

CONCLUSION

Gravity alters the hepatic architecture during body postural changes, causing outflow blockage in hepatic veins. A rigid liver is resistant to structural deformation. Stiff-liver softening in the Ld position suggests a fibrous liver.

Keywords: Shear wave elastography; Inferior vena cava diameter; Congestive hepatopathy; Liver fibrosis; Body positions; Fibrosis-4 index

Core Tip: Medical progress ironically makes the liver a prognostic determinant in patients with congenital heart diseases because there are no effective biomarkers to evaluate pathological progression in congestive hepatopathy. A canonical liver stiffness measurement cannot screen for fibrous liver under congestion because congestion itself makes the liver stiff without fibrosis. Here, we report a simple strategy of liver stiffness measurement to identify clues to liver fibrosis even under congestion. The basic data presented in this report provide insights not only for the clinical application of liver stiffness in patients with congestive heart diseases but also for the physiological components and mechanisms underlying liver stiffness.