Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2022; 28(20): 2214-2226
Published online May 28, 2022. doi: 10.3748/wjg.v28.i20.2214
Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid-enhanced magnetic resonance imaging for evaluating fibrosis regression in chronic hepatitis C patients after direct-acting antiviral
Xiao-He Li, Rui Huang, Ming Yang, Jian Wang, Ying-Hui Gao, Qian Jin, Dan-Li Ma, Lai Wei, Hui-Ying Rao
Xiao-He Li, Rui Huang, Ming Yang, Jian Wang, Ying-Hui Gao, Qian Jin, Dan-Li Ma, Lai Wei, Hui-Ying Rao, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Peking University People’s Hospital, Beijing 100044, China
Ming Yang, Lai Wei, Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 100044, China
Author contributions: Li XH, Rao HY and Wei L designed the protocol of this study; Li XH, Huang R, Yang M, Wang J, Gao YH, Jin Q and Ma DL collected the data; Li XH analyzed and interpreted the patient data and was major contributors in writing the manuscript; Wei L and Rao HY give advice in study design, statistical analysis and writing the manuscript; All authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81870406; and Nature Science Foundation of Beijing Municipality, No. 7182174.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of Peking University People’s Hospital (2020PHB039-01), and the requirement for patient informed consent was waived.
Informed consent statement: Patients were not required to provide informed consent for this study, as the analysis used anonymous clinical data. The Institutional Review Board of Peking University People’s Hospital approved waiving the requirement for patient informed consent.
Conflict-of-interest statement: Prof. Rao reports grants from National Natural Science Foundation of China (NSFC), No. 81870406, and Beijing Natural Science Foundation, No. 7182174 during the conduct of the study.
Data sharing statement: No additional data are available.
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: Hui-Ying Rao, MD, Chief Doctor, Professor, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Peking University People’s Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing 100044, China. rao.huiying@163.com
Received: September 30, 2021
Peer-review started: September 30, 2021
First decision: March 11, 2022
Revised: March 25, 2022
Accepted: April 21, 2022
Article in press: April 21, 2022
Published online: May 28, 2022
Processing time: 239 Days and 3.3 Hours
Abstract
BACKGROUND

Direct acting antiviral (DAA) therapy has enabled hepatitis C virus infection to become curable, while histological changes remain uncontained. Few valid non-invasive methods can be confirmed for use in surveillance. Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) is a liver-specific magnetic resonance imaging (MRI) contrast, related to liver function in the hepatobiliary phase (HBP). Whether Gd-EOB-DTPA-enhanced MRI can be used in the diagnosis and follow up of hepatic fibrosis in patients with chronic hepatitis C (CHC) has not been investigated.

AIM

To investigate the diagnostic and follow-up values of Gd-EOB-DTPA-enhanced MRI for hepatic histology in patients with CHC.

METHODS

Patients with CHC were invited to undergo Gd-EOB-DTPA-enhanced MRI and liver biopsy before treatment, and those with paired qualified MRI and liver biopsy specimens were included. Transient elastography (TE) and blood tests were also arranged. Patients treated with DAAs who achieved 24-wk sustained virological response (SVR) underwent Gd-EOB-DTPA-enhanced MRI and liver biopsy again. The signal intensity (SI) of the liver and muscle were measured in the unenhanced phase (UEP) (SIUEP-liver, SIUEP-muscle) and HBP (SIHBP-liver, SIHBP-muscle) via MRI. The contrast enhancement index (CEI) was calculated as [(SIHBP-liver/SIHBP-muscle)]/[(SIUEP-liver/SIUEP-muscle)]. Liver stiffness measurement (LSM) was confirmed with TE. Serologic markers, aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4), were also calculated according to blood tests. The grade of inflammation and stage of fibrosis were evaluated with the modified histology activity index (mHAI) and Ishak fibrosis score, respectively. Fibrosis regression was defined as a ≥ 1-point decrease in the Ishak fibrosis score. The correlation between the CEI and liver pathology was evaluated. The diagnostic and follow-up values of the CEI, LSM, and serologic markers were compared.

RESULTS

Thirty-nine patients with CHC were enrolled [average age, 42.3 ± 14.4 years; 20/39 (51.3%) male]. Twenty-one enrolled patients had eligible paired Gd-EOB-DTPA-enhanced MRI and liver tissues after achieving SVR. The mHAI median significantly decreased after SVR [baseline 6.0 (4.5-13.5) vs SVR 2.0 (1.5-5.5), Z = 3.322, P = 0.017], but the median stage of fibrosis did not notably change (P > 0.05). Sixty pairs of qualified MRI and liver tissue samples were available for use to analyze the relationship between the CEI and hepatic pathology. The CEI was negatively correlated with the mHAI (r = -0.56, P < 0.001) and Ishak score (r = -0.69, P < 0.001). Further stratified analysis showed that the value of the CEI decreased with the progression of the stage of fibrosis rather than with the grade of necroinflammation. For patients with Ishak score ≥ 5, the areas under receiver operating characteristics curve of the CEI, LSM, APRI, and FIB-4 were approximately at baseline, 0.87–0.93, and after achieving SVR, 0.83–0.91. The CEI cut-off value was stable (baseline 1.58 and SVR 1.59), but those of the APRI (from 1.05 to 0.24), FIB-4 (from 1.78 to 1.28), and LSM (from 10.8 kpa to 7.1 kpa) decreased dramatically. The APRI and FIB-4 cannot be used as diagnostic means for SVR in patients with Ishak score ≥ 3 (P > 0.05). Seven patients achieved fibrosis regression after achieving SVR. In these patients, the CEI median increased (from 1.71 to 1.83, Z = -1.981, P = 0.048) and those of the APRI (from 1.71 to 1.83, Z = -2.878, P = 0.004) and LSM (from 6.6 to 4.8, Z = -2.366, P = 0.018) decreased. However, in patients without fibrosis regression, the medians of the APRI, FIB-4, and LSM also changed significantly (P < 0.05).

CONCLUSION

Gd-EOB-DTPA-enhanced MRI has good diagnostic value for staging fibrosis in patients with CHC. It can be used for fibrotic-change monitoring post SVR in patients with CHC treated with DAAs.

Keywords: Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid-enhanced magnetic resonance imaging; Contrast enhancement index; Hepatitis C virus; Direct acting antiviral; Sustained virological response; Fibrosis regression

Core Tip: In this prospective, comparative study, the correlation between the contrast enhancement index (CEI) in the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid enhanced magnetic resonance imaging and liver pathology measures was analyzed in patients with chronic hepatitis C. It was determined that the CEI has good diagnostic performance and is more useful than serological markers and transient elastography for hepatic-fibrosis monitoring in patients achieving sustained virological response.