Miyake Teruki, Furukawa Shinya, Matsuura Bunzo, Yoshida Osamu, Kanamoto Ayumi, Miyazaki Masumi, Shiomi Akihito, Nakaguchi Hironobu, Okazaki Yuki, Nakamura Yoshiko, Imai Yusuke, Koizumi Mitsuhito, Watanabe Takao, Yamamoto Yasunori, Koizumi Yohei, Tokumoto Yoshio, Hirooka Masashi, Kumagi Teru, Abe Masanori, Hiasa Yoichi
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon City, Ehime 791-0295, Japan.
Health Services Center, Ehime University, 3 Bunkyocho, Matsuyama City, Ehime 790-0826, Japan.
J Clin Endocrinol Metab. 2025 May 19;110(6):e2064-e2070. doi: 10.1210/clinem/dgae597.
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.
We aimed to elucidate the relationship between accurately measured serum Rem-C levels and histological findings of MASLD.
Cross-sectional single-center observational study.
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.
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.
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.
估计残余胆固醇（Rem-C）水平是心血管疾病的一个危险因素，与通过超声诊断的代谢功能障碍相关脂肪性肝病（MASLD）有关。然而，准确的血清Rem-C水平测量与MASLD组织学结果之间的关系仍不清楚。
我们旨在阐明准确测量的血清Rem-C水平与MASLD组织学结果之间的关系。
横断面单中心观察性研究。
我们评估了222例患者（94例男性和128例女性；年龄20 - 80岁），这些患者通过肝活检被诊断为MASLD，并有可用的病史、体格检查和生化测量数据。使用酶法测量残余脂蛋白中的血清酯型胆固醇和游离胆固醇含量。
非酒精性脂肪性肝病活动评分（NAS）为5至8、脂肪变性分级>66%、小叶炎症≥5个病灶以及许多细胞/显著气球样变细胞（连续一片显示显著气球样变损伤的肝细胞）的患者血清Rem-C水平显著高于NAS为1至4、脂肪变性分级<33%、小叶炎症<2个病灶以及少量气球样变细胞（几个散在的气球样细胞）的患者。虽然单因素分析显示Rem-C水平与晚期纤维化之间无显著关联，但Rem-C水平与NAS之间存在显著关联。在调整混杂因素的多因素分析中，这种关系仍然显著。此外，按性别分析时，这些关系在男性中显著，但在女性中不显著。
高血清Rem-C水平与高NAS相关，但与纤维化阶段无关，尤其是在男性中。控制血清Rem-C水平可能改善MASLD的活动。
