Lisco Giuseppe, Guido Davide, Cerabino Nicole, Di Chito Martina, Donvito Rosanna, Bonfiglio Caterina, Shahini Endrit, Zappimbulso Marianna, Randazzo Cristiana, Barletta Domenico, Stabile Dolores, Ancona Anna, Coletta Sergio, Pesole Pasqua Letizia, Giannelli Gianluigi, De Pergola Giovanni
Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy.
Unit of Data Science, National Institute of Gastroenterology "Saverio de Bellis", IRCCS Hospital, Castellana Grotte, Bari, 70013, Italy.
J Transl Med. 2025 Apr 29;23(1):487. doi: 10.1186/s12967-025-06464-9.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of steatotic liver disease and has major implications on cardiovascular safety.
As the precise role linking MASLD to cardiovascular diseases is still unclear, the present study aims to investigate the association between liver steatosis and fibrosis and circulating plasminogen activator inhibitor-1 (PAI-1) levels.
Eighty-two patients (41.6 ± 12.4 yrs, 34 men, 41%), naïve to medications, who attended the Nutrition Center for the Research and Care of Obesity and Metabolic Diseases at the National Institute of Gastroenterology "Saverio de Bellis" for weight management, were cross-sectionally evaluated. Demographic, anthropometric, clinic, and laboratory data were collected and analyzed. All patients underwent liver ultrasonographic assessment by FibroScan to diagnose liver steatosis (controlled attenuation parameter or CAP > 275 dBm) and fibrosis (liver stiffness > 8.2 kPa).
Sixty-one individuals (74.4%) had liver steatosis, and 17 (20.7%) had liver fibrosis. PAI-1 mean levels were 3,261 ± 1,270 pg/mL, mean body mass index (BMI) and waist circumference (WC) values were 36.6 ± 7.1 kg/m and 114.1 ± 16.5 cm, respectively. Mild systolic and diastolic arterial pressure elevation and significantly high values of fasting plasma insulin (19.6 ± 12.6 IU/mL) and homeostatic model assessment of insulin resistance or HOMA-IR (4.8 ± 3.5) were also found. CAP values were correlated with several anthropometric, clinical, and laboratory parameters of insulin resistance. We found a significant association between PAI-1 and CAP (β = 1.605; p = 0.004), and noteworthily, when PAI-1 increased by 100 units, the expected variation of CAP values was by + 1.6 units (p = 0.004). Notably, the association was independent of gender, age, and insulin resistance.
Circulating PAI-1 levels are correlated with liver steatosis and, to a lesser extent, fibrosis in apparently healthy patients with a BMI ≥ 25 kg/m. This is the first study to show these results in patients naïve to medications, using FibroScan assessment. The bidirectional relationship between circulating PAI-1 levels and CAP measurement highlights the relevance of our research from a diagnostic and pathophysiological-prognostic viewpoint. Longitudinal trials are needed to clarify the cause-effect association between MASLD and PAI-1 levels.
代谢功能障碍相关脂肪性肝病（MASLD）是脂肪性肝病最常见的病因，对心血管安全有重大影响。
由于MASLD与心血管疾病之间的确切联系仍不清楚，本研究旨在探讨肝脏脂肪变性和纤维化与循环纤溶酶原激活物抑制剂-1（PAI-1）水平之间的关联。
对82例未服用过药物的患者（年龄41.6±12.4岁，男性34例，占41%）进行横断面评估，这些患者前往国立胃肠病研究所“Saverio de Bellis”的肥胖与代谢疾病研究与护理营养中心进行体重管理。收集并分析人口统计学、人体测量学、临床和实验室数据。所有患者均通过FibroScan进行肝脏超声评估，以诊断肝脏脂肪变性（控制衰减参数或CAP＞275 dBm）和纤维化（肝脏硬度＞8.2 kPa）。
61例个体（74.4%）有肝脏脂肪变性，17例（20.7%）有肝纤维化。PAI-1平均水平为3261±1270 pg/mL，平均体重指数（BMI）和腰围（WC）值分别为36.6±7.1 kg/m²和114.1±16.5 cm。还发现轻度收缩压和舒张压升高，以及空腹血浆胰岛素（19.6±12.6 IU/mL）和胰岛素抵抗稳态模型评估（HOMA-IR）（4.8±3.5）显著升高。CAP值与胰岛素抵抗的多个体测量学、临床和实验室参数相关。我们发现PAI-1与CAP之间存在显著关联（β=1.605；p=0.004），值得注意的是，当PAI-1增加100个单位时，CAP值的预期变化为+1.6个单位（p=0.004）。值得注意的是，这种关联独立于性别、年龄和胰岛素抵抗。
在BMI≥25 kg/m²的明显健康患者中，循环PAI-1水平与肝脏脂肪变性相关，在较小程度上与肝纤维化相关。这是第一项使用FibroScan评估在未服用过药物的患者中显示这些结果的研究。循环PAI-1水平与CAP测量值之间的双向关系从诊断和病理生理预后的角度突出了我们研究的相关性。需要进行纵向试验来阐明MASLD与PAI-1水平之间的因果关系。
