Zhu Na, Li Yanyan, Lin Yingying, Cui XinYu, Li Xin
Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Center of Integrative Medicine, Peking University Ditan Teaching Hospital, Beijing, China.
Front Nutr. 2025 Jun 6;12:1549089. doi: 10.3389/fnut.2025.1549089. eCollection 2025.
The development of metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with cardiovascular health (CVH) status and chronic inflammation. Life's Crucial 9 (LC9) is the most recent index to assess CVH; its association with MASLD and liver fibrosis is unclear. This study aimed to investigate the association of LC9 with MASLD and hepatic fibrosis and to reveal for the first time the mediating role of a novel inflammatory marker, neutrophil percentage-to-albumin ratio (NPAR), in the association between LC9 and MASLD.
This study was a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. The United States Fatty Liver Index (US-FLI) ≥ 30 was used to diagnose MASLD, and liver stiffness measurement (LSM) > 8.2 is defined as liver fibrosis. Weighted multifactorial regression, restricted cubic spline analysis (RCS), and subgroup analyses were used to assess the association between LC9 and MASLD and liver fibrosis. Mediation analysis was used to explore the possible mediating role of NPAR in the association of LC9 with MASLD.
A total of 9,623 participants were included in this study. After adjusting for all confounders, LC9 was significantly and negatively associated with both MASLD (OR = 0.59, 95% CI: 0.54-0.64) and hepatic fibrosis (OR = 0.66, 95% CI: 0.45-0.97), with each 10-point increase in the LC9 score decreasing the prevalence by 41% and 34%, respectively. In subgroup analyses, interaction tests showed that age, education, deprivation, obesity, smoking, hypertension, diabetes, and hyperlipidemia significantly affected the association between LC9 and MASLD (P for interaction < 0.05). In addition, NPAR was positively associated with the prevalence of MASLD, with a 5% increase in the prevalence of MASLD for each unit increase in NPAR (OR = 1.05, 95% CI: 1.01-1.09). The positive association between NPAR and MASLD was stronger in younger age groups (<60 years), non-drinkers, and participants without diabetes or hyperlipidemia. Mediation analysis showed that NPAR mediated 2.84% of the association between LC9 and MASLD ( < 0.001).
Good CVH status (high LC9 score) was associated with lower prevalence of MASLD and liver fibrosis, and NPAR partially mediated the association between LC9 and MASLD. This study provides new epidemiological evidence for preventing MASLD by improving CVH and inflammatory modulation.
代谢功能障碍相关脂肪性肝病（MASLD）的发展与心血管健康（CVH）状况和慢性炎症密切相关。生命关键9项指标（LC9）是评估CVH的最新指标；其与MASLD和肝纤维化的关联尚不清楚。本研究旨在探讨LC9与MASLD和肝纤维化的关联，并首次揭示一种新型炎症标志物——中性粒细胞百分比与白蛋白比值（NPAR）在LC9与MASLD关联中的中介作用。
本研究对2005年至2018年美国国家健康与营养检查调查（NHANES）的数据进行横断面分析。采用美国脂肪肝指数（US-FLI）≥30诊断MASLD，肝脏硬度测量值（LSM）>8.2定义为肝纤维化。采用加权多因素回归、受限立方样条分析（RCS）和亚组分析评估LC9与MASLD及肝纤维化的关联。采用中介分析探讨NPAR在LC9与MASLD关联中的可能中介作用。
本研究共纳入9623名参与者。在调整所有混杂因素后，LC9与MASLD（OR=0.59，95%CI：0.54-0.64）和肝纤维化（OR=0.66，95%CI：0.45-0.97）均呈显著负相关，LC9评分每增加10分，患病率分别降低41%和34%。在亚组分析中，交互作用检验显示年龄、教育程度、贫困程度、肥胖、吸烟、高血压、糖尿病和高脂血症显著影响LC9与MASLD之间的关联（交互作用P<0.05）。此外，NPAR与MASLD患病率呈正相关，NPAR每增加一个单位，MASLD患病率增加5%（OR=1.05，95%CI：1.01-1.09）。NPAR与MASLD之间的正相关在较年轻年龄组（<60岁）、不饮酒者以及无糖尿病或高脂血症的参与者中更强。中介分析显示，NPAR介导了LC9与MASLD之间2.8
