Sex-specific differences in cardiometabolic risk factors may influence the likelihood of clinically significant liver fibrosis, according to a study of US adults published in JAMA Network Open. Researchers found that several metabolic risk factors – particularly central adiposity, glucose intolerance, and the presence of multiple cardiometabolic conditions – were associated with higher odds of fibrosis in women compared with men.
The cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020 and included 5,981 adults aged 20 years or older with valid transient elastography measurements. Clinically significant fibrosis was defined as liver stiffness of at least 8.0 kPa measured by transient elastography.
Overall, significant fibrosis was observed in 6.9 percent of women and 10.7 percent of men. Despite this lower overall prevalence in women, some cardiometabolic risk factors were more strongly associated with fibrosis in women than in men.
High waist circumference – defined as greater than 102 cm in men or 88 cm in women – showed a stronger association with fibrosis in women. In adjusted analyses, the odds of significant fibrosis were more than 13 times higher in women with high waist circumference compared with those without, while the odds were about four times higher in men.
Glucose intolerance was also associated with higher odds of fibrosis, with adjusted odds ratios of 2.94 in women and 1.51 in men. In addition, the presence of two or more cardiometabolic risk factors – including abdominal obesity, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol levels, or glucose intolerance – was associated with higher odds of fibrosis in both sexes but was more strongly associated in women.
Among the study population, women had a higher prevalence of elevated waist circumference (69.0 percent) compared with men (48.6 percent). Men had higher rates of glucose intolerance and hypertriglyceridemia. Overall obesity rates were similar between the groups.
The investigators also conducted several sensitivity analyses, including analyses limited to participants with severe steatosis, those without excessive alcohol use, and those with metabolic dysfunction–associated steatotic liver disease. The main findings were generally consistent across these analyses.
The authors noted that the cross-sectional design prevents determination of causality and that fibrosis staging relied on noninvasive elastography rather than histopathology.
The findings highlight potential sex differences in the relationship between cardiometabolic risk factors and liver fibrosis and may inform future approaches to fibrosis risk assessment in patients with metabolic risk factors.
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