The liver-brain axis in metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects around 30% of the global population. Studies suggest that MASLD is associated with compromised brain health and cognitive dysfunction, initiating a growing interest in exploring the liver-brain axis mechanistically within MASLD pathophysiology. With the prevalence of MASLD increasing at an alarming rate, leaving a large proportion of people potentially at risk, cognitive dysfunction in MASLD is a health challenge that requires careful consideration and awareness. This Review summarises the current literature on cognitive function in people with MASLD and discusses plausible causes for its impairment. It is likely that a multifaceted spectrum of factors works collectively to affect cognition in patients with MASLD. We describe the role of inflammation, vascular disease, and brain ageing and neurodegeneration as possible key players. This Review also highlights the need for future studies to identify the optimal test for diagnosing cognitive dysfunction in patients with MASLD, to examine the correlation between MASLD progression and the severity of cognitive dysfunction, and to evaluate whether new MASLD-targeted therapies also improve brain dysfunction.