Page 83 - Read Online

Byrne et al. Metab Target Organ Damage 2024;4:10 https://dx.doi.org/10.20517/mtod.2024.06 Page 5 of 7

therapy with resmetirom targeting the liver and other added agents to attenuate the high CVD risk or treat
T2DM and/or obesity. This approach to treating MAFLD/MASLD as a multisystem disease with
combination therapy might, therefore, additionally include incretin receptor agonists, sodium-glucose
cotransporter-2 inhibitors, statins, and renin-angiotensin-system inhibitors. Additionally, in certain
patients, treatment with pioglitazone, which is effective in the treatment of NASH/MASH, may be
[36]
considered . Emphasizing the centrality of metabolic dysfunction and measuring MetS features should also
be beneficial. Such an emphasis should highlight to non-specialists and patients that the treatment of
NAFLD/MAFLD/MASLD (as a multisystem disease) requires a multidisciplinary and holistic approach
focused on addressing metabolic dysfunction. When considering treatments, targeting metabolic
dysfunction and measuring and treating specific MetS characteristics (e.g., hypertension, dyslipidemia and
obesity, and type 2 diabetes), should help clinicians focus their attention beyond the liver.

DECLARATIONS
Authors’ contributions
Agreed on the concept and content: Byrne CD, Targher G
Wrote the first draft: Byrne CD
Contributed to the writing and editing: Targher G
Agreed on the final submitted version: Byrne CD, Targher G

Availability of data and materials
Not applicable.

Financial support and sponsorship
No funding was received for this study. GT was supported in part by grants from the School of Medicine,
University of Verona, Verona, Italy. CDB was supported in part by the Southampton National Institute for
Health and Care Research Biomedical Research Centre (NIHR203319), UK.

Conflicts of interest
Christopher D. Byrne and Giovanni Targher are the Honorary Editors-in-Chief of the journal Metabolism
and Target Organ Damage. They declared that there are no other conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2024.

REFERENCES
1. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease.
Mayo Clin Proc 1980;55:434-8. PubMed
2. Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol 2015;62:S47-64. DOI
3. Targher G, Tilg H, Byrne CD. Non-alcoholic fatty liver disease: a multisystem disease requiring a multidisciplinary and holistic
approach. Lancet Gastroenterol Hepatol 2021;6:578-88. DOI PubMed
4. Mantovani A, Byrne CD, Bonora E, Targher G. Nonalcoholic fatty liver disease and risk of incident type 2 diabetes: a meta-analysis.
Diabetes Care 2018;41:372-82. DOI PubMed
5. Mantovani A, Csermely A, Petracca G, et al. Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an
updated systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2021;6:903-13. DOI