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Non-invasive methods for imaging hepatic steatosis and their clinical importance in NAFLD

Nature Reviews Endocrinology volume 18, pages 55–66 (2022)Cite this article

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Abstract

Hepatic steatosis is a key histological feature of nonalcoholic fatty liver disease (NAFLD). The non-invasive quantification of liver fat is now possible due to advances in imaging modalities. Emerging data suggest that high levels of liver fat and its temporal change, as measured by quantitative non-invasive methods, might be associated with NAFLD progression. Ultrasound-based modalities have moderate diagnostic accuracy for liver fat content and are suitable for screening. However, of the non-invasive imaging modalities, MRI-derived proton density fat fraction (MRI-PDFF) has the highest diagnostic accuracy and is used for trial enrolment and to evaluate therapeutic effects in early-phase clinical trials in nonalcoholic steatohepatitis (NASH). In patients with NAFLD without advanced fibrosis, high levels of liver fat are associated with rapid disease progression. Furthermore, changes on MRI-PDFF (≥30% decline relative to baseline) are associated with NAFLD activity score improvement and fibrosis regression. However, an inverse association exists between liver fat and complications of cirrhosis. Liver fat decreases as liver fibrosis progresses towards cirrhosis, and the clinical importance of quantitative measurements of liver fat differs by NAFLD status. As such, patients with NAFLD should be stratified by fibrosis severity to investigate the utility of quantitative measurements of liver fat for assessing NAFLD progression and prognosis.

Key points

  • Ultrasound-based modalities for the quantification of liver fat content have moderate diagnostic accuracy for the degree of hepatic steatosis and are useful as a pre-screen strategy in clinical trials in nonalcoholic steatohepatitis (NASH).

  • Compared with other imaging modalities, MRI-derived proton density fat fraction (MRI-PDFF) has the highest diagnostic accuracy for quantification of liver fat content and is commonly used in trials in NASH.

  • Increased liver fat content (MRI-PDFF ≥15%) is associated with increased odds of fibrosis progression in patients with NAFLD at an early stage of fibrosis.

  • In patients with NAFLD, change in MRI-PDFF (≥30% decline relative to baseline) is associated with a histological response (NAFLD activity score ≥2 points improvement with no worsening of fibrosis) and fibrosis regression (reduction of one or more stages).

  • Decreased liver fat content is associated with an increased incidence of liver-related events and poor prognosis in patients with NASH with advanced fibrosis.

  • Liver fat content decreases in the setting of cirrhosis; therefore, the clinical importance of quantitative assessment of liver fat content and its change over time differs by NAFLD disease status and fibrosis severity.

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Fig. 1: Accumulation of lipids in the liver and disease progression in NAFLD.
Fig. 2: Two-step liver fat content assessment to reduce screen failure rate in trials in NASH.
Fig. 3: Clinical importance of quantitative liver fat content assessment in NAFLD.

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Acknowledgements

R.L. acknowledges the support of funding from NIEHS (5P42ES010337), NCATS (5UL1TR001442), DOD PRCRP (W81XWH-18-2-0026), NIDDK (U01DK061734, R01DK106419, R01DK121378, R01DK124318, P30DK120515), NHLBI (P01HL147835) and NIAAA (U01AA029019). V.A. acknowledges the support of funding from NIDDK (K23DK119460). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. N.T. acknowledges the support of funding from the Uehara Memorial Foundation (201940021).

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Authors and Affiliations

  1. NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, USA

    Nobuharu Tamaki, Veeral Ajmera & Rohit Loomba

  2. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan

    Nobuharu Tamaki

  3. The Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA

    Rohit Loomba

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  1. Nobuharu Tamaki
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  2. Veeral Ajmera
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  3. Rohit Loomba
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The authors contributed equally to all aspects of the article.

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Correspondence to Rohit Loomba.

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Competing interests

R.L. serves as a consultant or advisory board member for Anylam/Regeneron, Arrowhead Pharmaceuticals, AstraZeneca, Bird Rock Bio, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Cirius, CohBar, Conatus, Eli Lilly, Galmed, Gemphire, Gilead, Glympse bio, GNI, GRI Bio, Inipharm, Intercept, Ionis, Janssen Inc., Merck, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Prometheus, Promethera, Sanofi, Siemens, and Viking Therapeutics. In addition, his institution has received grant support from Allergan, Boehringer-Ingelheim, Bristol-Myers Squibb, Cirius, Eli Lilly and Company, Galectin Therapeutics, Galmed Pharmaceuticals, GE, Genfit, Gilead, Intercept, Grail, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, NuSirt, Pfizer, pH Pharma, Prometheus, and Siemens. He is also co-founder of Liponexus, Inc. The other authors declare no competing interests.

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Nature Reviews Endocrinology thanks M. Romero-Gomez who co-reviewed with R. Montero Vallejo, S. Petta, K. Tokushige and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Tamaki, N., Ajmera, V. & Loomba, R. Non-invasive methods for imaging hepatic steatosis and their clinical importance in NAFLD. Nat Rev Endocrinol 18, 55–66 (2022). https://doi.org/10.1038/s41574-021-00584-0

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