Hepatic cholesterol accumulation

Hepatic cholesterol accumulation is a pathological condition characterized by the abnormal buildup of free cholesterol and its esters within liver cells (Ioannou, 2016). While cholesterol is vital for cellular function, its excessive presence in the liver is a key driver of lipotoxicity, oxidative stress, and mitochondrial dysfunction (Musso et al., 2013). This accumulation is a central feature in the pathogenesis of Metabolic dysfunction-associated steatotic liver disease (MASLD) and can trigger the progression to Metabolic dysfunction-associated steatohepatitis (MASH) through inflammatory and fibrogenic pathways (Rinella et al., 2023). Although not a single molecular target, this process is managed by drugs that target specific proteins involved in cholesterol homeostasis, such as HMG-CoA reductase (inhibited by statins) and NPC1L1 (inhibited by ezetimibe) (Grundy et al., 2019). Reducing hepatic cholesterol levels is essential for preventing advanced liver diseases like cirrhosis and hepatocellular carcinoma, as well as reducing systemic cardiovascular risk (Puri et al., 2007). Therapeutic strategies often aim to balance cholesterol influx, synthesis, and efflux to mitigate liver injury.

Other names

Liver cholesterol buildupHepatic cholesterol overloadIntrahepatic cholesterol accumulationHepatic cholesterol deposition

Pharmacological agents reduce hepatic cholesterol accumulation by inhibiting de novo synthesis via HMG-CoA reductase, blocking intestinal absorption via NPC1L1, or promoting biliary excretion and LDL receptor-mediated clearance (Grundy et al., 2019; Altmann et al., 2004).