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. 2021 Jan 27:11:575843.
doi: 10.3389/fendo.2020.575843. eCollection 2020.

Correlations Between MRI Biomarkers PDFF and cT1 With Histopathological Features of Non-Alcoholic Steatohepatitis

Andrea Dennis  1 , Matt D Kelly  1 , Carolina Fernandes  1 , Sofia Mouchti  1 , Jonathan A Fallowfield  2 , Gideon Hirschfield  3 , Michael Pavlides  4   5   6 , Stephen Harrison  4   7 , Manu V Chakravarthy  8 , Rajarshi Banerjee  1 , Arun Sanyal  9
Affiliations

Correlations Between MRI Biomarkers PDFF and cT1 With Histopathological Features of Non-Alcoholic Steatohepatitis

Andrea Dennis et al. Front Endocrinol (Lausanne). .

Abstract

Introduction: Late stage clinical trials in non-alcoholic steatohepatitis (NASH) are currently required by the FDA to use liver biopsy as a primary endpoint. The well-reported limitations with biopsy, such as associated risks and sampling error, coupled with patient preference, are driving investigation into non-invasive alternatives. MRI-derived biomarkers proton density fat fraction (PDFF) and iron-corrected T1 mapping (cT1) are gaining traction as emerging alternatives to biopsy for NASH. Our aim was to explore the correlations between cT1 and PDFF (from LiverMultiScan®), with the histological components on the NAFLD-NASH spectrum in a large cohort of cross-sectional data, in order to calibrate the measurement to histology, and to infer what might constitute a clinically meaningful change when related to the FDA's criteria.

Materials and methods: In a retrospective analysis of data combined from three previously published observational NASH studies, in which adult participants who underwent liver biopsy on suspicion of NAFLD or NASH and had an MRI scan measuring cT1 and PDFF (LiverMultiScan®, Perspectum Ltd, UK), associations between imaging biomarkers and histology were tested using Spearman's rank correlation coefficient (rs), and further exploration of the relationships between the imaging variables and histology were performed using linear regression.

Results: N = 264 patients with mean age of 54 (SD:9.9), 39% female, and 69% with BMI ≥ 30kg.m-2 were included in the analysis. cT1 and PDFF both correlated with all features of the NAFLD activity score (NAS). cT1 was also positively correlated with Kleiner-Brunt fibrosis. Partial correlations, adjusting for steatosis, revealed cT1 correlated with inflammation and fibrosis, whereas PDFF did not, and both were still associated with the NAS, but correlation was weaker with PDFF than cT1. An estimated difference of 88 ms in cT1, or 21% relative difference in PDFF was related to a two-point difference in overall NAS.

Conclusion: The correlations between cT1 and PDFF with the histopathological hallmarks of NASH demonstrate the potential utility of both cT1 and PDFF as non-invasive biomarkers to detect a pharmacodynamic change in NASH, with cT1 showing superiority for detecting changes in inflammation and fibrosis, rather than liver fat alone.

Trial registration: ClinicalTrials.gov NCT01543646 NCT03142867.

Keywords: MRI; NAFLD; NASH; imaging; non-invasive biomarkers.

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Conflict of interest statement

Perspectum Ltd is a privately funded commercial enterprise that develops medical devices to address unmet clinical needs, including LiverMultiScan®. RB is the CEO and founder of Perspectum. AD, SM, CF, and MK are employees of Perspectum. MP is a shareholder in Perspectum. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of patient inclusion from the three trials RIAL/NICOLA, CALM, and PREVALENCE.
Figure 2
Figure 2
Example PDFF and cT1 parametric maps for patients with NAS = 1 (A) cT1 = 684ms, PDFF = 6.5%; NAS = 3 (B) cT1 = 833ms, PDFF = 16.9%; and NAS = 5 (C) cT1 = 916ms, PDFF = 18.5%.
Figure 3
Figure 3
Box plots showing relationships between cT1 and PDFF with NAS (top row) and fibrosis (bottom row).
See this image and copyright information in PMC

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References

    1. Marra F, Lotersztajn S. Pathophysiology of NASH: Perspectives for a Targeted Treatment. Curr Pharm Des (2013) 19:5250–69. 10.2174/13816128113199990344 - DOI - PMC - PubMed
    1. Younossi Z, Koenig A, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease— meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology (2016) 64(1):73–84. 10.1002/hep.28431 - DOI - PubMed
    1. Younossi Z, Anstee Q, Marietti M, Hardy T, Henry L, Eslam M, et al. Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol (2018) 15(1):11–20. 10.1038/nrgastro.2017.109 - DOI - PubMed
    1. Cholankeril G, Ahmed A. Alcoholic Liver Disease Replaces Hepatitis C Virus Infection as the Leading Indication for Liver Transplantation in the United States. Clin Gastroenterol Hepatol (2018) 16(8):1356–8. 10.1016/j.cgh.2017.11.045 - DOI - PMC - PubMed
    1. Noureddin M, Nissen AV, Bresee C, Todo T, Kim I, Alkhouri N, et al. NASH Leading Cause of Liver Transplant in Women: Updated Analysis of Indications For Liver Transplant and Ethnic and Gender Variances. Am J Gastroenterol (2018) 113(11):1649–59. 10.1038/s41395-018-0088-6 - DOI - PMC - PubMed

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