Sex-Specific Cardiometabolic Profiles and Severity of Liver Fibrosis

TL;DR

The study finds that women with multiple heart and metabolism risk factors face a higher risk of liver fibrosis than men, suggesting the need for sex-specific screening.

Contribution

The study reveals sex-specific differences in how cardiometabolic risk factors are linked to liver fibrosis risk.

Findings

Women with high waist circumference had a 3x higher risk of liver fibrosis compared to men.

Having two or more cardiometabolic risk factors increased fibrosis risk more in women than in men.

Glucose intolerance was more strongly associated with fibrosis in women than in men.

Abstract

This cross-sectional study investigates differences between men and women in the association of cardiometabolic risk factors with significant liver fibrosis.

Are there sex-specific differences in associations between cardiometabolic risk factors and significant liver fibrosis among US adults?

In this cross-sectional study of 5981 US adults from the 2017 to 2020 National Health and Nutrition Examination Survey, women had higher odds of clinically significant fibrosis in association with central adiposity, glucose intolerance, and the presence of multiple cardiometabolic risk factors compared with men.

These findings suggest that women with multiple cardiometabolic risk factors may face a disproportionately higher risk of liver fibrosis, supporting the need for sex-specific screening and prevention strategies.

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.

To examine sex differences in the association between individual CMRFs and significant liver fibrosis among US adults.

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.

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.

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.

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).

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.

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