Hepatic neurons and metabolically induced liver dysfunction

Hepatic nerves have an underexplored role in liver function. The global prevalence of liver disease has reached unprecedented levels, with over 1.6 billion individuals affected by metabolic dysfunction-associated steatotic liver disease (MASLD). A comprehensive understanding of these liver disease mechanisms is essential for identifying the aetiologies of such conditions. Studies from the past 5 years suggest that hepatic nerves might influence the progression of MASLD to metabolic dysfunction-associated steatohepatitis and hepatocellular carcinoma. As MASLD advances, hepatic sympathetic activity increases while hepatic sympathetic innervation diminishes. Conversely, both parasympathetic and sympathetic innervation might contribute to hepatic fibrosis and liver dysfunction. This Review examines the function of hepatic neurons, their modulation by metabolic disease and the potential to target these mechanisms to develop novel treatments for liver diseases.