Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May;23(5):1069-1083.
doi: 10.1111/dom.14322. Epub 2021 Feb 10.

Nonalcoholic fatty liver disease as a metabolic disease in humans: A literature review

Bertrand Cariou  1 , Christopher D Byrne  2   3 , Rohit Loomba  4 , Arun J Sanyal  5
Affiliations

Nonalcoholic fatty liver disease as a metabolic disease in humans: A literature review

Bertrand Cariou et al. Diabetes Obes Metab. 2021 May.

Abstract

Aims: To conduct a systematic literature review to identify recent epidemiological, biomarker, genetic and clinical evidence that expands our understanding of nonalcoholic fatty liver disease (NAFLD) as a metabolic disorder.

Materials and methods: We performed a literature search using PubMed to identify trials, observational studies and meta-analyses published in the past 5 years.

Results: A total of 95 publications met prespecified inclusion criteria and reported on the interplay between NAFLD/nonalcoholic steatohepatitis (NASH) and metabolic dysfunction, in terms of disease burden and/or epidemiology (n = 10), pathophysiology, risk factors and associated conditions (n = 29), diagnosis and biomarkers (n = 34), and treatment approaches (n = 22). There is a growing body of evidence on the links between NAFLD/NASH pathogenesis and mechanisms of metabolic dysfunction, through liver lipid accumulation, insulin resistance, inflammation, apoptosis, and fibrogenic remodelling within the liver. The frequent co-occurrence of NAFLD with obesity, metabolic syndrome and type 2 diabetes supports this premise. Therapeutic approaches originally envisaged for type 2 diabetes or obesity (such as glucagon-like peptide-1 receptor agonists, sodium-glucose co-transporter-2 inhibitors, insulin sensitizers and bariatric surgery) have shown promising signs of benefit for patients with NAFLD/NASH.

Conclusions: Given the complex interplay between NAFLD and metabolic dysfunction, there is an urgent need for multidisciplinary collaboration and established protocols for care of patients with NAFLD that are individualized and ideally support reduction of overall metabolic risk as well as treatment for NASH.

Keywords: GLP-1; fatty liver disease; insulin resistance; pharmaco-epidemiology; type 2 diabetes.

PubMed Disclaimer

Conflict of interest statement

B. C. reports grants and personal fees from Amgen, Regeneron and Sanofi, and personal fees from Abbott, Akcea, AstraZeneca, Bristol Myers Squibb, Genfit, Gilead, Eli Lilly and Company, Merck (MSD) and Novo Nordisk. R. L. serves as a consultant or advisory board member for 89bio, Alnylam, Arrowhead Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cirius, CohBar, DiCerna, Galmed, Gilead, Glympse bio, Intercept, Ionis, Metacrine, NGM Biopharmaceuticals, Novo Nordisk, Pfizer, Sagimet and Viking Therapeutics. In addition, his institution has received grant support from Allergan, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Galmed Pharmaceuticals, Genfit, Gilead, Intercept, Inventiva, Janssen, Madrigal Pharmaceuticals, NGM Biopharmaceuticals, Novartis, Pfizer, pH Pharma and Siemens. He is also co‐founder of Liponexus, Inc. A. J. S. is President of Sanyal Biotechnology and has stock options in Genfit, Akarna, Tiziana, Indalo, Durect Inversago and Galmed. He has served as a consultant to AstraZeneca, Nitto Denko, Conatus, Nimbus, Salix, Tobira, Takeda, Janssen, Gilead, Terns, Birdrock, Merck, Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Hemoshear, Zafgen, Novartis, Novo Nordisk, Pfizer, Exhalenz and Genfit. He has been an unpaid consultant to Intercept, Echosens, Immuron, Galectin, Fractyl, Syntlogic, Affimune, Chemomab, Zydus, Nordic Bioscience, Albireo, Prosciento and Surrozen. His institution has received grant support from Gilead, Salix, Tobira, Bristol Myers Squibb, Shire, Intercept, Merck, AstraZeneca, Malinckrodt, Cumberland and Novartis. He receives royalties from Elsevier and UptoDate. C. D. B. discloses no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Diagram of included and excluded publications
FIGURE 2
FIGURE 2
Potential mechanisms by which nonalcoholic steatohepatitis (NASH) causes hepatic and extrahepatic metabolic dysfunction and current metabolic therapeutic targets. Acetyl‐CoA, acetyl co‐enzyme A; GLP‐1, glucagon‐like peptide‐1; HR, hormone receptor; NAFLD, non‐alcoholic fatty liver disease; PPAR, peroxisome proliferator‐activated receptor; SGLT2, sodium‐glucose co‐transporter‐2; T2DM, type 2 diabetes mellitus
See this image and copyright information in PMC

References

    1. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328‐357. - PubMed
    1. European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO) . EASL‐EASD‐EASO clinical practice guidelines for the management of non‐alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388‐1402. - PubMed
    1. Takahashi Y, Fukusato T. Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2014;20(42):15539‐15548. - PMC - PubMed
    1. Dulai PS, Singh S, Patel J, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta‐analysis. Hepatology. 2017;65(5):1557‐1565. - PMC - PubMed
    1. Hashimoto E, Taniai M, Tokushige K. Characteristics and diagnosis of NAFLD/NASH. J Gastroenterol Hepatol. 2013;28(4 Suppl):64‐70. - PubMed

Publication types

MeSH terms

Substances