Sex-Specific Cardiometabolic Profiles and Severity of Liver Fibrosis.

Importance: Advanced liver fibrosis is increasing globally, with women experiencing faster progression despite lower prevalence. Cardiometabolic risk factors (CMRFs) may be differentially associated with fibrosis risk by sex. Objective: To examine sex differences in the association between individual CMRFs and significant liver fibrosis among US adults. Design, Setting, and Participants: This population-based, cross-sectional study was conducted using data from the US National Health and Nutrition Examination Survey, 2017 to 2020. Adults aged 20 years or older with valid transient elastography measurements were included. Data were analyzed from July 2024 through December 2025. Exposures: CMRFs, including high waist circumference (>102 cm in men or 88 cm in women), glucose intolerance, hypertension, hypertriglyceridemia, and low high-density lipoprotein cholesterol levels, were assessed, as well as obesity (body mass index ≥30 or ≥27.5 for Asian participants) and the presence of 2 or more CMRFs. Main Outcomes and Measures: Clinically significant fibrosis was defined as a liver stiffness of 8.0 kPa or greater by transient elastography. Multivariable logistic regression evaluated associations between CMRFs and significant fibrosis, adjusting for age, sex, race and ethnicity, smoking, and alcohol and testing CMRF by sex interactions. Results: The study population of 5981 participants included 2992 women (weighted percentage: 50.2% [95% CI, 48.2%-52.2%]; 14.7% Hispanic [95% CI, 12.0%-18.0%], 11.0% non-Hispanic Black [95% CI, 8.2%-14.7%], and 65.0% non-Hispanic White [95% CI, 59.4%-70.3%]; mean age, 49 years [95% CI, 48-50 years]) and 2989 men (weighted percentage: 49.8% [95% CI, 47.8%-51.8%]; 16.4% Hispanic [95% CI, 13.2%-20.2%], 9.4% non-Hispanic Black [95% CI, 7.3%-11.9%], and 64.6% non-Hispanic White [95% CI, 59.6%-69.3%]; mean age, 47 years [95% CI, 46-48 years]). Women had higher prevalence of high waist circumference (69.0% [95% CI, 66.1%-71.7%] vs 48.6% [95% CI, 44.3%-53.1%]) and lower prevalence of hypertension (41.0% [95% CI, 38.2%-43.8%] vs 44.9% [95% CI, 41.5%-48.4%]), glucose intolerance (31.1% [95% CI, 28.7%-33.5%] vs 41.7% [95% CI, 38.6%-44.9%]), and hypertriglyceridemia (36.6% [95% CI, 34.0%-39.3%] vs 48.8% [95% CI, 44.6%-52.9%]) compared with men. The prevalence of significant fibrosis was 6.9% (95% CI, 5.4%-8.8%) in women and 10.7% (95% CI, 8.8%-12.9%) in men. The point estimates in the association with significant fibrosis were significantly greater in women vs men for high waist circumference (adjusted odds ratio [aOR], 13.45 [95% CI, 5.70-31.78] vs aOR, 4.44 [95% CI, 3.00-6.57]; P for interaction = .01), glucose intolerance (aOR, 2.94 [95% CI, 1.64-5.28] vs aOR, 1.51 [95% CI, 1.08-2.13]; P for interaction = .045), and the presence of 2 or more CMRFs (aOR, 10.22 [95% CI, 4.76-21.95] vs aOR, 2.87 [95% CI, 1.91-4.31]; P for interaction = .002). Conclusions and Relevance: In this study, the presence of 2 or more CMRFs was associated with a greater increase in risk of significant fibrosis for women compared with men. Central adiposity and glucose intolerance were also associated with greater increases in risk among women.. These findings support the need for sex-specific screening approaches.