Division of Gastroenterology, Department of Medicine, Washington University in Saint Louis, St. Louis, MO, 53110, USA.
Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Dig Dis Sci. 2023 Aug;68(8):3451-3457. doi: 10.1007/s10620-023-07980-8. Epub 2023 Jun 8.
Genetic mutations causing defective VLDL secretion and low LDL cholesterol are associated with hepatic steatosis and nonalcoholic fatty liver disease (NAFLD).
Determine if low LDL cholesterol (< 5th percentile) was an independent predictor of hepatic steatosis.
Secondary data analysis of the Dallas Heart study (an urban, multiethnic, probability-based sample), we defined hepatic steatosis utilizing intrahepatic triglyceride (IHTG) analyzed using magnetic resonance spectroscopy in conjunction and available demographic, serological and genetic information. We exclude patients on lipid lowering medications.
Of the 2094 subjects that met our exclusion criteria, 86 had a low LDL cholesterol, of whom 19 (22%) exhibited hepatic steatosis. After matching for age, sex, BMI, and alcohol consumption, low LDL cholesterol was not a risk factor for hepatic steatosis compared to those with normal (50-180 mg/dL) or high (> 180 mg/dL) LDL. When analyzed as a continuous variable, we observed lower IHTG in the low LDL group compared to the normal or high LDL groups (2.2%, 3.5%, 4.6%; all pairwise comparisons p < 0.001). Subjects with both hepatic steatosis and low LDL cholesterol exhibited a more favorable lipid profile but similar insulin resistance and hepatic fibrosis risk compared to other subjects with hepatic steatosis. The distribution of variant alleles associated with NAFLD, including PNPLA3, GCKR, and MTTP was indistinguishable between subjects with hepatic steatosis and low versus high LDL cholesterol.
These findings suggest that low serum LDL levels are not a useful predictor of hepatic steatosis and NAFLD. Moreover, subjects with low LDL exhibit a more favorable lipid profile and lower IHTG.
导致 VLDL 分泌缺陷和 LDL 胆固醇降低的基因突变与肝脂肪变性和非酒精性脂肪性肝病（NAFLD）有关。
确定 LDL 胆固醇水平低（<第 5 百分位数）是否是肝脂肪变性的独立预测因子。
对达拉斯心脏研究（一项城市、多民族、基于概率的样本）的二次数据分析，我们使用磁共振波谱分析结合可用的人口统计学、血清学和遗传信息来定义肝脂肪变性。我们排除正在服用降脂药物的患者。
在符合我们排除标准的 2094 名受试者中，有 86 人 LDL 胆固醇低，其中 19 人（22%）患有肝脂肪变性。在匹配年龄、性别、BMI 和饮酒量后，与 LDL 正常（50-180mg/dL）或高（>180mg/dL）的患者相比，LDL 胆固醇低并不是肝脂肪变性的危险因素。当作为连续变量进行分析时，我们观察到 LDL 胆固醇低组的 IHTG 低于正常或高 LDL 组（2.2%、3.5%、4.6%；所有两两比较均 p<0.001）。与其他患有肝脂肪变性的患者相比，同时患有肝脂肪变性和 LDL 胆固醇低的患者表现出更有利的血脂谱，但胰岛素抵抗和肝纤维化风险相似。与 NAFLD 相关的变异等位基因的分布，包括 PNPLA3、GCKR 和 MTTP，在 LDL 胆固醇低与高的肝脂肪变性患者之间没有区别。
这些发现表明，血清 LDL 水平低不能作为肝脂肪变性和 NAFLD 的有用预测因子。此外，LDL 胆固醇低的患者表现出更有利的血脂谱和更低的 IHTG。
