Noninvasive biomarkers in NAFLD and NASH — current progress and future promise

Abstract

Nonalcoholic fatty liver disease (NAFLD) affects 25% of the global adult population and is the most common chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is the active form of NAFLD, with hepatic necroinflammation and faster fibrosis progression. With an increasing number of patients developing NASH-related end-stage liver disease and pharmacological treatments on the horizon, there is a pressing need to develop NAFLD and NASH biomarkers for prognostication, selection of patients for treatment and monitoring. This requirement is particularly true as liver biopsy utility is limited by its invasive nature, poor patient acceptability and sampling variability. This article reviews current and potential biomarkers for different features of NAFLD, namely, steatosis, necroinflammation and fibrosis. For each biomarker, we evaluate its accuracy, reproducibility, responsiveness, feasibility and limitations. We cover biochemical, imaging and genetic biomarkers and discuss biomarker discovery in the omics era.

Key points

  • When assessing a patient with nonalcoholic fatty liver disease (NAFLD), the key histological features of interest include the degree of steatosis, necroinflammation and fibrosis.

  • MRI-estimated proton density fat fraction is currently the most accurate test to quantify hepatic steatosis and can be considered the gold standard.

  • Magnetic resonance elastography is the most accurate fibrosis test, yet its use is limited by cost and availability.

  • Controlled attenuation parameter and liver stiffness measurement by transient elastography also enables simultaneous assessment of hepatic steatosis and fibrosis, albeit with lower accuracy and success rates than MRI-based methods.

  • Plasma cytokeratin 18 (CK18) fragment levels are a marker of hepatocyte apoptosis and represent the most extensively evaluated biomarker of steatohepatitis, although the accuracy is modest.

  • A number of gene polymorphisms (such as those in PNPLA3 and TM6SF2) have been shown to correlate with NAFLD and its severity, yet their role in patient assessment remains to be established.

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Fig. 1: Management of NAFLD according to disease severity.
Fig. 2: Ultrasound-based measurement of liver stiffness or elasticity.
Fig. 3: Noninvasive assessment of NAFLD and NASH.

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Acknowledgements

The work of the authors was supported partially by grants PICT 2014–543 and PICT 2015–0551 (Agencia Nacional de Promoción Científica y Tecnológica) and the General Research Fund from the Research Grants Council, Hong Kong SAR Government (project reference 14108916). The authors thank C. Cassinotto and N. Frulio for the 2D shear wave elastography and point shear wave elastography images.

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Correspondence to Vincent Wai-Sun Wong.

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V.W.-S.W. served as a consultant for AbbVie, Allergan, Gilead Sciences, Janssen, Perspectum Diagnostics and Pfizer and a speaker for Bristol-Myers Squibb, Echosens, Gilead Sciences and Merck. L.A.A. has received speaking fees from Bayer and holds patents for Hepascore (Quest Diagnostics) for which his employer (University of Western Australia) has received royalties from Quest Diagnostics for its commercialization. V.d.L. has served as a consultant for AbbVie, Bristol-Myers Squibb, Echosens, Gilead Sciences, Merck, Intercept Pharma and Supersonic Imagine and a speaker for AbbVie, Bristol-Myers Squibb, Echosens, Gilead Sciences, Intercept Pharma and Merck. G.L.-H.W. has served as an advisory committee member for Gilead Sciences and a speaker for Abbott, AbbVie, Bristol-Myers Squibb, Echosens, Furui, Gilead Sciences, Janssen and Roche. S.S. declares no competing interests.

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Wong, V.W., Adams, L.A., de Lédinghen, V. et al. Noninvasive biomarkers in NAFLD and NASH — current progress and future promise. Nat Rev Gastroenterol Hepatol 15, 461–478 (2018). https://doi.org/10.1038/s41575-018-0014-9

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