The prevalence of nonalcoholic fatty liver disease (NAFLD) has progressively increased over recent decades with increased rates of obesity and the rapid growth of the ageing population, affecting approximately 29% of the Chinese population (1). In addition to intrahepatic diseases such as liver cirrhosis and hepatocellular carcinoma, NAFLD has been demonstrated to increase the risks of multiple extrahepatic complications, including type 2 diabetes (T2DM), chronic kidney disease, cardiovascular disease (CVD), and even extrahepatic tumours (2,3). Recently, a multisociety Delphi consensus statement has proposed replacing NAFLD with metabolic-associated steatotic liver disease (MASLD) (4). More and more evidences show that the natural history of MASLD is identical to NAFLD (5,6). Notably, patients with MASLD have not received sufficient attention due to the absence of any obvious signs or symptoms in the early stages. Considering the burden of MASLD, a deeper understanding of the pathophysiology and risk factors related to MASLD has become imperative for early intervention.

Dyslipidaemia is most common in patients with NAFLD. Convincing evidence shows that NAFLD is often related to and accompanied by high levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C) (7,8). Remnant cholesterol (RC) is the cholesterol content of triglyceride-rich lipoproteins and can be indirectly calculated by TC minus LDL-C minus HDL-C (9). Current research suggests that high serum RC levels increase the risks of cardiovascular disease (CVD), hypertension, diabetes mellitus, and metabolic syndrome, all of which are correlated with NAFLD (10, 11, 12). Recently, several cross-sectional studies from China and Australia revealed that there was a positive association between serum RC levels and NAFLD, independent of traditional lipid parameters (13,14). Furthermore, a longitudinal prospective cohort study reported that nonobese populations with high serum RC levels had a higher risk of developing NAFLD (15). However, evidence regarding the relationship between baseline serum RC levels and MASLD transitions is yet to be elucidated. Moreover, whether high serum RC levels increase the risk of liver fibrosis in MASLD patients remains unknown.

Therefore, we extend previous findings and provide a cross-sectional study to investigate the association of serum RC levels with the severity of hepatic steatosis and liver fibrosis evaluated by transient elastography. Simultaneously, we conducted a longitudinal cohort study to evaluate the associations of serum RC levels with the progression and regression of MASLD.