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.

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

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.

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.