活组织检查证实代谢功能障碍相关脂肪变性肝病患者血清去氨甾醇水平反映肝脏炎症等级

IF 2.8 2区医学 Q2 PERIPHERAL VASCULAR DISEASE

Journal of atherosclerosis and thrombosis Pub Date : 2025-07-16 DOI:10.5551/jat.65748

Takashi Omatsu, Masahiro Koseki, Kaori Ito, Ayami Saga, Hiroshi Sawabe, Katsunao Tanaka, Hiroyasu Inui, Takeshi Okada, Makoto Nishida, Hirokazu Takahashi, Shinichi Aishima, Yoshihiro Kamada, Hiroshi Yoshida, Yasushi Sakata

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引用次数: 0

摘要

目的：去氨甾醇，一种胆固醇前体，通过Δ24-dehydrocholesterol还原酶转化。因此，去氨甾醇水平被认为反映胆固醇代谢。本研究旨在评估甾醇作为亚洲中度肥胖代谢功能障碍相关脂肪变性肝病（MASLD）患者肝脏状况的新生物标志物。方法：共纳入218例接受肝活检的MASLD患者。肝活检样本由精通的病理学家根据标准进行评估。采用液相色谱-质谱法分析活检证实的MASLD患者的血清甾醇，如去氨甾醇、谷甾醇和油菜甾醇。结果：8/107/90/12例患者为0/1/2/3级炎症，25/48/64/63/17例患者为0/1/2/3/4级纤维化。血清去氨甾醇水平在炎症等级0-3级之间存在显著差异（单因素方差分析[ANOVA]， p = 0.004）， β系数为0.219（95%可信区间[CI]: 0.088-0.350, p<0.01）。经其他参数校正后，炎症等级的有序logistic回归分析数据显示，去氨甾醇的优势比为3.727 （95% CI 1.422 ~ 9.901, p<0.005）。尽管去氨甾醇水平受到他汀类药物治疗的影响，但在未接受他汀类药物治疗的患者中，血清去氨甾醇水平因炎症等级而存在显著差异（单因素方差分析，p = 0.041）， β系数为0.233 （95% CI: 0.066-0.400, p<0.01）。结论：血清去氨甾醇水平反映了MASLD患者肝脏炎症活动的程度。由于去氨甾醇是核受体LXR的配体，反映了肝脏胆固醇代谢，我们希望我们的研究结果将有助于建立一种新的生物标志物来筛选MASLD中心血管疾病的高危患者。

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Serum Desmosterol Level Reflects Hepatic Inflammation Grade in Patients with Biopsy-Confirmed Metabolic Dysfunction-Associated Steatotic Liver Disease.

Aim: Desmosterol, a cholesterol precursor, is converted by Δ24-dehydrocholesterol reductase. Hence, desmosterol levels are considered to reflect cholesterol metabolism. This study aimed to evaluate sterols as novel biomarkers of liver condition in Asian moderate obese patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: In total, 218 patients with MASLD who underwent liver biopsy were prospectively enrolled. Liver biopsy samples were evaluated by a well-versed pathologist according to the criteria. The serum sterols of biopsy-proven patients', such as desmosterol, sitosterol, and campesterol, of the patients with biopsy-proven MASLD were analyzed using liquid chromatography-mass spectrometry.

Results: Inflammation grade 0/1/2/3 was observed in 8/107/90/12 patients, and fibrosis stage 0/1/2/3/4 was observed in 25/48/64/63/17 patients, respectively. Serum desmosterol levels were significantly different by inflammation grade 0-3 (one-way analysis of variance [ANOVA], p = 0.004), with a beta coefficient of 0.219 (95% confidence interval [CI]: 0.088-0.350, p＜0.01). Ordinal logistic regression analysis data on inflammation grade, adjusted for other parameters, showed that desmosterol had an odds ratio of 3.727 (95% CI 1.422-9.901, p＜0.005). Although desmosterol levels are influenced by statin treatment, in non-statin-treated patients, serum desmosterol levels remained significantly different by inflammation grade (one-way ANOVA, p = 0.041), and the beta coefficient was 0.233 (95% CI: 0.066-0.400, p＜0.01).

Conclusions: Serum desmosterol levels indicated the degree of hepatic inflammatory activity in patients with MASLD. Since desmosterol, a ligand of nuclear receptor LXR, reflects hepatic cholesterol metabolism, we hope that our findings will contribute to establishing a novel biomarker to screen the high-risk patients for cardiovascular diseases in MASLD.

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