Assessment of Liver Fibrosis Using the Coefficient of Variation on Gadoxetic Acid-Enhanced Hepatobiliary Phase MR Imaging: A Prospective Multicenter Study
7 affiliations
- 1Department of Radiology, Wonkwang University Hospital, 895 Muwang-ro, Iksan 54538, Jeollabuk-do, Republic of Korea
- 2Medical Convergence Research Center, Wonkwang University, 460 Iksandae-ro, Iksan 54538, Jeollabuk-do, Republic of Korea
- 3Department of Internal Medicine, Wonkwang University Hospital, 895 Muwang-ro, Iksan 54538, Jeollabuk-do, Republic of Korea
- 4Department of Pathology, Wonkwang University Hospital, 895 Muwang-ro, Iksan 54538, Jeollabuk-do, Republic of Korea
- 5Department of Radiology, Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun 58128, Jeollanam-do, Republic of Korea
- 6Department of Radiology, Asan Medical Center, 88 Olympic-ro 43-gil, Seoul 05505, Republic of Korea
- 7Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Seoul 05505, Republic of Korea
Abstract
Background: Accurate non-invasive assessment of liver fibrosis is needed in patients with chronic liver disease. Gadoxetic acid (Gd-EOB-DTPA)-enhanced hepatobiliary phase (HBP) magnetic resonance (MR) imaging reflects hepatocyte function and parenchymal heterogeneity, and the coefficient of variation (CV), which quantifies pixel-level signal inhomogeneity, has been proposed as a quantitative imaging biomarker of liver fibrosis. However, previous studies were retrospective, single-center, and lacked direct pathological validation. Objectives: To investigate the factors associated with CV on HBP images, evaluate the correlation between CV and pathologically confirmed liver fibrosis stage, and compare the diagnostic performance of CV with serum biomarkers, including the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4), in a prospective multicenter setting. Methods: This prospective multicenter study was conducted between April 2017 and August 2020 at three medical centers. Ninety-nine participants who underwent Gd-EOB-DTPA-enhanced HBP T1-weighted MRI and liver biopsy or surgery were enrolled. CV was measured on HBP images, and the METAVIR fibrosis stage was used as the reference standard. Univariate and multivariable linear regression analyses, including an additional model adjusted for institution and pathology confirmation method, Welch’s analysis of variance with the Games–Howell post hoc test, Spearman’s rank correlation analysis, receiver operating characteristic (ROC) curve analysis with DeLong’s method for AUROC comparison, and intraclass correlation coefficient (ICC) analyses were performed. Results: Ninety-nine participants (64 men and 35 women; mean age, 55.5 ± 15.1 years) were enrolled. In multivariable linear regression analysis adjusted for institution and pathology confirmation method, pathologic fibrosis stage (B = 0.468; 95% CI, 0.358–0.578; p < 0.001) and serum albumin level (B = −0.341; p = 0.015) were independently associated with CV. Spearman’s correlation coefficient between CV and fibrosis stage was 0.74 (p < 0.001). The AUROCs of CV for significant fibrosis (≥F2), advanced fibrosis (≥F3), and cirrhosis (F4) were 0.92, 0.88, and 0.86, respectively (all p < 0.001). CV outperformed APRI and FIB-4 across most fibrosis thresholds (p < 0.001 to p = 0.045), except for FIB-4 in the diagnosis of ≥F2 fibrosis (p = 0.09). The intra- and inter-observer ICC values were 0.94 and 0.84, respectively. Conclusions: In this prospective multicenter study with pathologically confirmed fibrosis stages, CV derived from Gd-EOB-DTPA-enhanced HBP MR images showed a strong correlation with liver fibrosis stage and higher diagnostic performance than APRI and FIB-4 across most fibrosis thresholds. Because CV can be calculated from routine clinical MRI acquisitions without additional hardware or blood tests, it may serve as a practical biomarker for non-invasive liver fibrosis assessment. However, because this study was conducted in a Korean cohort with predominantly hepatitis B virus-related liver disease, further validation in other ethnic groups and etiologies is needed.
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BibTeX
@article{kim2026assessment,
title = {{Assessment of Liver Fibrosis Using the Coefficient of Variation on Gadoxetic Acid-Enhanced Hepatobiliary Phase MR Imaging: A Prospective Multicenter Study}},
author = {Youe Ree Kim and Tae-Hoon Kim and Chang-Won Jeong and Young Hwan Lee and Eun Young Cho and Keum Ha Choi and Yong Yeon Jeong and Suk Hee Heo and Kyung Won Kim and Yousun Ko and Youngbin Shin and Dong Min Kang and Kwon-Ha Yoon},
journal = {Journal of Clinical Medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15207996},
url = {https://www.mdpi.com/2077-0383/15/20/7996},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Assessment of Liver Fibrosis Using the Coefficient of Variation on Gadoxetic Acid-Enhanced Hepatobiliary Phase MR Imaging: A Prospective Multicenter Study
AU - Youe Ree Kim
AU - Tae-Hoon Kim
AU - Chang-Won Jeong
AU - Young Hwan Lee
AU - Eun Young Cho
AU - Keum Ha Choi
AU - Yong Yeon Jeong
AU - Suk Hee Heo
AU - Kyung Won Kim
AU - Yousun Ko
AU - Youngbin Shin
AU - Dong Min Kang
AU - Kwon-Ha Yoon
PY - 2026
DA - 2026/10/01
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15207996
UR - https://www.mdpi.com/2077-0383/15/20/7996
AB - Background: Accurate non-invasive assessment of liver fibrosis is needed in patients with chronic liver disease. Gadoxetic acid (Gd-EOB-DTPA)-enhanced hepatobiliary phase (HBP) magnetic resonance (MR) imaging reflects hepatocyte function and parenchymal heterogeneity, and the coefficient of variation (CV), which quantifies pixel-level signal inhomogeneity, has been proposed as a quantitative imaging biomarker of liver fibrosis. However, previous studies were retrospective, single-center, and lacked direct pathological validation. Objectives: To investigate the factors associated with CV on HBP images, evaluate the correlation between CV and pathologically confirmed liver fibrosis stage, and compare the diagnostic performance of CV with serum biomarkers, including the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4), in a prospective multicenter setting. Methods: This prospective multicenter study was conducted between April 2017 and August 2020 at three medical centers. Ninety-nine participants who underwent Gd-EOB-DTPA-enhanced HBP T1-weighted MRI and liver biopsy or surgery were enrolled. CV was measured on HBP images, and the METAVIR fibrosis stage was used as the reference standard. Univariate and multivariable linear regression analyses, including an additional model adjusted for institution and pathology confirmation method, Welch’s analysis of variance with the Games–Howell post hoc test, Spearman’s rank correlation analysis, receiver operating characteristic (ROC) curve analysis with DeLong’s method for AUROC comparison, and intraclass correlation coefficient (ICC) analyses were performed. Results: Ninety-nine participants (64 men and 35 women; mean age, 55.5 ± 15.1 years) were enrolled. In multivariable linear regression analysis adjusted for institution and pathology confirmation method, pathologic fibrosis stage (B = 0.468; 95% CI, 0.358–0.578; p < 0.001) and serum albumin level (B = −0.341; p = 0.015) were independently associated with CV. Spearman’s correlation coefficient between CV and fibrosis stage was 0.74 (p < 0.001). The AUROCs of CV for significant fibrosis (≥F2), advanced fibrosis (≥F3), and cirrhosis (F4) were 0.92, 0.88, and 0.86, respectively (all p < 0.001). CV outperformed APRI and FIB-4 across most fibrosis thresholds (p < 0.001 to p = 0.045), except for FIB-4 in the diagnosis of ≥F2 fibrosis (p = 0.09). The intra- and inter-observer ICC values were 0.94 and 0.84, respectively. Conclusions: In this prospective multicenter study with pathologically confirmed fibrosis stages, CV derived from Gd-EOB-DTPA-enhanced HBP MR images showed a strong correlation with liver fibrosis stage and higher diagnostic performance than APRI and FIB-4 across most fibrosis thresholds. Because CV can be calculated from routine clinical MRI acquisitions without additional hardware or blood tests, it may serve as a practical biomarker for non-invasive liver fibrosis assessment. However, because this study was conducted in a Korean cohort with predominantly hepatitis B virus-related liver disease, further validation in other ethnic groups and etiologies is needed.
SN - 2077-0383
ER -