The prognostic value of including non-alcoholic fatty liver disease in the definition of metabolic syndrome

Clarissa Elysia Fu, Jie Ning Yong, Cheng Han Ng, Benjamin Nah, Nicholas W.S. Chew, Yip Han Chin, Gwyneth Kong, Darren Jun Hao Tan, Wen Hui Lim, Lincoln Kai En Lim, Rebecca Wenling Zeng, Asim Shabbir, Eunice X.X. Tan, Daniel Q. Huang, Chin Meng Khoo, Mohammad Shadab Siddqui, Mark Y.Y. Chan, Mazen Noureddin, Mamas A. Mamas, Mark Muthiah

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Background/Aims: Metabolic syndrome (MetS) affects over one third of the US adult population. Despite its close association with non-alcoholic fatty liver disease (NAFLD), the traditional definition of MetS does not account for the presence of NAFLD. The present study thus aims to evaluate the inclusion of NAFLD in the diagnostic criteria of metabolic syndrome on its accuracy of capturing individuals with metabolic dysregulation and its prediction of adverse events. Methods: Data collected from NHANES between 1999 and 2018 was analysed. Clinical characteristics and outcomes between individuals with metabolic syndrome from both the American Heart Association/National Heart, Lung, and Blood Institute (MetS) and the study's proposed diagnostic criteria (MetS2) were evaluated. Outcomes in both groups were evaluated with multivariate analyses, and further subgroup analysis on individuals matched with Coarsened Exact Matching was performed. Results: Of 46,184 individuals included, 32.54% and 40.54% fulfilled MetS and MetS2 criteria respectively. Considering NAFLD in the definition of metabolic syndrome, a further 8.00% (n = 3694) were included. MetS was significantly associated with all-cause (HR: 1.184, 95% CI: 1.110–1.263, p < 0.001) and cardiovascular disease (CVD) mortality (SHR: 1.288, 95% CI: 1.233–1.347, p < 0.001), and major adverse cardiovascular events (MACE). MetS2 was similarly associated with all-cause (HR: 1.175, 95% CI: 1.088–1.269, p < 0.001), CVD mortality (SHR: 1.283, 95% CI: 1.245–1.323, p < 0.001) and MACE. Conclusion: Inclusion of NAFLD allows for identification a greater proportion of the population with metabolic risk. This allows for early intervention and potential to lift some burden off the global healthcare system.

Original languageEnglish (US)
Pages (from-to)979-987
Number of pages9
JournalAlimentary Pharmacology and Therapeutics
Issue number9
StatePublished - May 2023


  • Metabolic disease
  • diagnostic criteria
  • fatty liver

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)


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