Association between serum remnant cholesterol level and metabolic dysfunction-associated steatotic liver histology

Abstract Context Estimated remnant cholesterol (Rem-C) level, a risk factor for cardiovascular disease, is associated with metabolic dysfunction-associated steatotic liver disease (MASLD) diagnosed via ultrasonography. However, the relationship between accurate serum Rem-C level measurements and histological findings of MASLD remains unclear. Objective We aimed to elucidate the relationship between accurately measured serum Rem-C levels and histological findings of MASLD. Design Cross-sectional single-center observational study. Methods We assessed 222 patients (94 men and 128 women; age 20-80) who were diagnosed with MASLD via liver biopsy with available medical history, physical examination, and biochemical measurement data. Serum ester-type cholesterol and free cholesterol contents in the remnant lipoproteins were measured using an enzymatic method. Results Serum Rem-C levels were significantly higher in patients with NAFLD activity score (NAS) 5 to 8, >66% steatosis grade, lobular inflammation with ≥5 foci, and many cells/prominent ballooning cells (a contiguous patch of hepatocytes showing prominent ballooning injury) than in patients with NAS 1 to 4, < 33% steatosis grade, lobular inflammation with <2 foci, and few ballooning cells (several scattered balloon cells), respectively. While univariate analysis revealed no significant association between Rem-C levels and advanced fibrosis, a significant association between Rem-C levels and NAS was evident. This relationship remained significant in multivariate analysis adjusted for confounders. Furthermore, in the analysis by sex, these relationships were significant for men but not for women. Conclusion High serum Rem-C levels were associated with high NAS but not with fibrosis stage, particularly in men. Controlling serum Rem-C level may improve MASLD activity.