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  • Review Article
  • Published:

Noninvasive evaluation of NAFLD

Abstract

A common clinical concern in patients with NAFLD is whether they have NASH or simple steatosis and, more importantly, what the stage of fibrosis is and whether the level of fibrosis has increased over time. Such concern is based on the fact that patients with NAFLD with advanced fibrosis are at greatest risk of developing complications of end-stage liver disease. Although it lacks sensitivity, ultrasonography is an accepted tool for steatosis screening. The controlled attenuation parameter or CAP seems a promising screening technique, but requires further validation. Cytokeratin-18 has been extensively validated, but it is an imperfect serum marker of NASH. Ultrasonography-based transient elastography can exclude advanced fibrosis and cirrhosis, but its main limitation is its reduced applicability in patients with NAFLD, which is not completely solved by use of the XL probe. Of the noninvasive serum markers, the NAFLD fibrosis score is the most validated and has appropriate accuracy in distinguishing patients with and without advanced fibrosis. Although noninvasive methods require further validation, they could be useful for selecting those patients with NAFLD who require a liver biopsy. This Review discusses the advantages and limitations of noninvasive methods for the management of adults with NAFLD, including diagnosis and quantification of steatosis, diagnosis of NASH and staging of hepatic fibrosis.

Key Points

  • Liver biopsy remains the reference standard for diagnosing NASH and staging fibrosis in patients with NAFLD

  • Identifying advanced fibrosis and cirrhosis is paramount as it dictates the need to screen for gastro-oesophageal varices and hepatocellular carcinoma

  • Noninvasive methods for fibrosis assessment rely on two different, but complementary, approaches: the biological approach based on serum biomarker levels and the physical approach based on liver stiffness (measured mainly using transient elastography)

  • The main limitation of ultrasonography-based transient elastography in clinical practice is its failure to obtain reliable liver stiffness measurements (20% of cases, mainly obese patients), which diminishes its application in NAFLD

  • The XL probe could be used as second line in the subset of patients in whom the regular (M) probe fails, but appropriate cut-off levels remain to be defined

  • Several biomarkers have been proposed to reliably identify advanced fibrosis and cirrhosis and could be useful to select patients with NAFLD who might benefit most from a liver biopsy

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Figure 1: Algorithm for noninvasive diagnosis of NAFLD.

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Acknowledgements

P. Angulo is supported in part by NIH R01 DK82426 grant.

Author information

Authors and Affiliations

Authors

Contributions

L. Castera researched data for the article. L. Castera, V. Vilgrain and P. Angulo made equal contributions to discussion of content and writing the article. L. Castera and P. Angulo reviewed and edited the manuscript before submission.

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Correspondence to Laurent Castera.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Performance of CAP using transient elastography for grading steatosis in patients with NAFLD (DOC 43 kb)

Supplementary Table 2

Performance of transient elastrography with the M probe for staging fibrosis in patients with NAFLD (DOC 50 kb)

Supplementary Table 3

Comparing the performance of transient elastrography with the XL and M probe for staging fibrosis in patients with NAFLD (DOC 40 kb)

Supplementary Table 4

Routine laboratory and clinical predictors of advanced fibrosis in patients with NAFLD (DOC 46 kb)

Supplementary Table 5

Serum markers of fibrogenesis and clinical predictors of advanced fibrosis (F3 4) in patients with NAFLD (DOC 61 kb)

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Castera, L., Vilgrain, V. & Angulo, P. Noninvasive evaluation of NAFLD. Nat Rev Gastroenterol Hepatol 10, 666–675 (2013). https://doi.org/10.1038/nrgastro.2013.175

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