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METABOLIC LIVER DISEASE IN 2020

Metabolic liver disease — what’s in a name?

Owing to the strong association of non-alcoholic fatty liver disease with obesity and cardiometabolic disease, in 2020 experts controversially proposed to rename this condition as ‘metabolic associated fatty liver disease’. Additional studies have elucidated new genetic and dietary modifiers of this disease. This knowledge is essential to improve diagnosis, risk-stratification and treatment.

Key advances

  • The largest genome-wide association study performed on liver biopsy samples to date confirmed a role for a variant in the PNPLA3 locus in the complete histological spectrum of non-alcoholic fatty liver disease and implicated PYGO1, a gene involved in hepatocellular development, in this condition3.

  • Preliminary data show that a machine learning algorithm efficiently quantified steatosis in population scale MRI data and helped define the role of genetic variants and environmental modifiers in hepatic steatosis, including a role for alcohol metabolism5.

  • Fructose metabolism within the small intestine regulates the delivery of fructose to the liver and the distal colon, which affects hepatic lipogenesis and steatosis8,9,10.

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References

  1. Eslam, M. et al. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology 158, 1999–2014 (2020).

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  2. Younossi, Z. M. et al. From NAFLD to MAFLD: implications of a premature change in terminology. Hepatology https://doi.org/10.1002/hep.31420 (2020).

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  7. Jensen, T. et al. Fructose and sugar: a major mediator of non-alcoholic fatty liver disease. J. Hepatol. 68, 1063–1075 (2018).

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  8. Andres-Hernando, A. et al. Deletion of fructokinase in the liver or in the intestine reveals differential effects on sugar-induced metabolic dysfunction. Cell Metab. 32, 117–127 (2020).

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  9. Jang, C. et al. The small intestine shields the liver from fructose-induced steatosis. Nat. Metab. 2, 586–593 (2020).

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  10. Zhao, S. et al. Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. Nature 579, 586–591 (2020).

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Acknowledgements

The author acknowledges the support of NIH R01-DK100425 and NIH R01-DK121710.

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Correspondence to Mark A. Herman.

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The author declares no competing interests.

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Herman, M.A. Metabolic liver disease — what’s in a name?. Nat Rev Endocrinol 17, 79–80 (2021). https://doi.org/10.1038/s41574-020-00452-3

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