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  • Year in Review
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NAFLD in 2022

NAFLD, MAFLD and obesity: brothers in arms?

2022 was a proficuous year in both the nonalcoholic fatty liver disease (NAFLD) and obesity fields. Pharmacological treatment for obesity and NAFLD is moving forward, with the possibility of replacing bariatric surgery, artificial intelligence might help us access the histological effects of new drugs, and there were advances in personalized hepatocellular carcinoma screening in patients with NAFLD.

Key advances

  • Artificial intelligence has been applied to quantify fibrosis reversal, using second harmonic generation–two-photon excitation fluorescence, after anti-nonalcoholic fatty liver disease (NAFLD) therapies3.

  • A dual incretin drug, tirzepatide, showed remarkable results in inducing weight loss, almost matching the results from bariatric surgery; tirzepatide also presented strong anti-steatogenic effects in the liver5.

  • A 133-gene hepatic transcriptome signature and 4-protein secretome signature stratify, with great accuracy, the risk for hepatocellular carcinoma in patients with NAFLD, with a high negative predictive value10.

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References

  1. Henry, L., Paik, J. & Younossi, Z. M. Review article: the epidemiologic burden of non-alcoholic fatty liver disease across the world. Aliment. Pharmacol. Ther. 56, 942–956 (2022).

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  2. Soon, G. & Wee, A. Updates in the quantitative assessment of liver fibrosis for nonalcoholic fatty liver disease: histological perspective. Clin. Mol. Hepatol. 27, 44–57 (2021).

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  3. Naoumov, N. V. et al. Digital pathology with artificial intelligence analyses provides greater insights into treatment-induced fibrosis regression in NASH. J. Hepatol. 77, 1399–1409 (2022).

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  4. Romero-Gómez, M., Zelber-Sagi, S. & Trenell, M. Treatment of NAFLD with diet, physical activity and exercise. J. Hepatol. 67, 829–846 (2017).

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  5. Gastaldelli, A. et al. Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diabetes Endocrinol. 10, 393–406 (2022).

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  6. Jastreboff, A. M. et al. Tirzepatide once weekly for the treatment of obesity. N. Engl. J. Med. 387, 205–216 (2022).

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  7. Hartman, M. L. et al. Effects of novel dual GIP and GLP-1 receptor agonist tirzepatide on biomarkers of nonalcoholic steatohepatitis in patients with type 2 diabetes. Diabetes Care 43, 1352–1355 (2020).

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  8. Orci, L. A. et al. Incidence of hepatocellular carcinoma in patients with nonalcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression. Clin. Gastroenterol. Hepatol. 20, 283–292 (2022).

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  9. Ioannou, G. N. Epidemiology and risk-stratification of NAFLD-associated HCC. J. Hepatol. 75, 1476–1484 (2021).

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  10. Fujiwara, N. et al. Molecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease. Sci. Transl Med. 14, eabo4474 (2022).

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Correspondence to Helena Cortez-Pinto.

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Competing interests

H.C.-P. declares lectures and advisory board fees from Intercept, Orphalan, Novo Nordisk, Roche Portugal and EISAI. M.V.M. declares no competing interests.

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NCT04166773: https://clinicaltrials.gov/ct2/show/NCT04166773

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Machado, M.V., Cortez-Pinto, H. NAFLD, MAFLD and obesity: brothers in arms?. Nat Rev Gastroenterol Hepatol 20, 67–68 (2023). https://doi.org/10.1038/s41575-022-00717-4

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