Clinical and Translational Research
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2021; 27(7): 609-623
Published online Feb 21, 2021. doi: 10.3748/wjg.v27.i7.609
Quantitative multiparametric magnetic resonance imaging can aid non-alcoholic steatohepatitis diagnosis in a Japanese cohort
Kento Imajo, Louise Tetlow, Andrea Dennis, Elizabeth Shumbayawonda, Sofia Mouchti, Timothy J Kendall, Eve Fryer, Shogi Yamanaka, Yasushi Honda, Takaomi Kessoku, Yuji Ogawa, Masato Yoneda, Satoru Saito, Catherine Kelly, Matt D Kelly, Rajarshi Banerjee, Atsushi Nakajima
Kento Imajo, Yasushi Honda, Takaomi Kessoku, Yuji Ogawa, Satoru Saito, Atsushi Nakajima, Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
Louise Tetlow, Andrea Dennis, Elizabeth Shumbayawonda, Sofia Mouchti, Catherine Kelly, Matt D Kelly, Rajarshi Banerjee, Innovation, Perspectum, Oxford OX4 2LL, United Kingdom
Timothy J Kendall, Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom, Edinburgh EH16 4TJ, United Kingdom
Eve Fryer, Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, United Kingdom
Shogi Yamanaka, Anatomic and Clinical Pathology Department, Yokohoma City University Hospital, Yokohoma 236-0004, Japan
Masato Yoneda, Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
Author contributions: Imajo K and Nakajima A developed the study concept, protocols and initiated the project; Kelly MD and Banerjee R assisted in the further development of the protocol and drafting the clinical study protocol; Imajo K, Nakajima A, Fryer E, Kendall TJ, Yamanaka S, Honda Y, Kessoku T, Ogawa Y, Yoneda M and Saito S contributed to the data collection; Tetlow L, Dennis AM, Shumbayawonda E to the data analysis; Imajo K, Tetlow L, Nakajima A, Dennis AM, Shumbayawonda E, Kelly C, Kelly MD and Banerjee R drafted and completed the manuscript. All authors contributed to the final manuscript.
Institutional review board statement: The study was conducted in accordance with the ethical principles of the Declaration of Helsinki 2013, was approved by the Ethics Committee of Yokohama City University Hospital and was registered as a clinical trial (UMIN Clinical Trials Registry: UMIN000026145).
Conflict-of-interest statement: Perspectum Ltd is a privately funded commercial enterprise that develops medical devices to address unmet clinical needs, including LiverMultiScan®. LT, ES, AD, MK are all employees of Perspectum. RB is CEO of Perspectum. KI, and AN have no relevant disclosures to this study. TK and EF undertake consultancy work for Perspectum.
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:
Corresponding author: Andrea Dennis, PhD, Research Scientist, Innovation, Perspectum, Gemini One, 5520 John Smith Drive, Oxford OX4 2LL, United Kingdom.
Received: August 28, 2020
Peer-review started: August 28, 2020
First decision: November 3, 2020
Revised: November 17, 2020
Accepted: December 28, 2020
Article in press: December 28, 2020
Published online: February 21, 2021
Research background

Non-alcoholic fatty liver disease affects 25% of the population worldwide and up to 30% in the Japanese population, and in some can progress to non-alcoholic steatohepatitis (NASH), a leading cause of liver transplant due to its strong propensity to develop into cirrhosis and hepatocellular carcinoma.

Research motivation

Liver biopsy is the current reference standard for a clinical diagnosis of NASH, a method that is expensive, invasive and suffers from great observer variability. Non-invasive and scalable alternatives are required in order to meet the burgeoning demands of the disease on clinical caseloads across the globe.

Research objectives

The main objectives of the study were to evaluate the diagnostic performance of non-invasive, image derived metrics to identify patients with suspected NASH. The metrics under investigation included two quantitative multi-parametric magnetic resonance imaging (MRI) measures, iron corrected T1 mapping [(cT1), a marker of fibro-inflammation] and proton density liver fat fraction (a marker of liver fat), magnetic resonance elastography and ultrasound based transient elastography (vibration-controlled transient elastography and 2D shear-wave elastography), both markers of liver stiffness.

Research methods

In an observational study of patients who were being screened clinically on suspicion of NASH, n = 145 individuals underwent liver biopsy and concomitant imaging measures of liver health. Diagnosis of NASH was based on histology, graded using the NAS- Clinical Research Network scoring system and diagnostic accuracy of the image-derived metrics assessed using area under receiver operator characteristic curve. In addition, the biopsy slides were read by 2 further pathologists and comparisons made to explore the level of agreement on diagnosis between individual doctors.

Research results

In this study assessing the ability of different non-invasive biomarkers to detect NASH, MR liver fat and cT1 were superior to the other metrics investigated. Crucially however, the composite marker of cT1 and MR liver fat showed the greatest diagnostic accuracy for identifying those with NASH and also those with NASH with fibrosis. These measures also had very few technical failures. This is the first assessment and direct comparison of these technologies in a Japanese cohort. We also observed discordance between different pathologists across the four cardinal pathological features (steatosis, ballooning, lobular inflammation and fibrosis), with no common pattern of agreement seen between any two pathologists.

Research conclusions

These results demonstrate the clinical utility of quantitative multiparametric magnetic resonance imaging (mpMRI) for the identification and stratification of patients with NASH from those with evidence of NAFLD and encourages mpMRI use as a non-invasive alternative to biopsy in the clinical care pathway. Quantitative mpMRI metrics showed the strongest correlation to the histological components of NASH with fewer technical failures. mpMRI also out-performed magnetic resonance elastography and ultrasound-based elastography methods in the identification of patients with NASH and fibrosis. Liver biopsy suffered from high levels of inter-reading disagreement, highlighting the pressing need for alternative diagnostic tests for NASH.

Research perspectives

The ability to risk stratify patients in a single non-invasive test is a particular strength of mpMRI, offering a safe and cost-effective alternative to liver biopsy. Future work should be focused on validating these findings further and on longer term outcomes studies to investigate the prognostic natures of these measurements in a Japanese population.