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Objective <p>Insulin resistance (IR) plays a critical role in shaping long-term outcomes in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Recent findings suggest that biological sex may influence the onset and progression of MASLD, yet it remains unclear whether sex modifies the link between IR and mortality in those with MASLD and advanced liver fibrosis.</p> Methods <p>We analyzed data from 14,081 MASLD patients (7327 men and 6754 women) drawn from the 2001–2018 cycles of the National Health and Nutrition Examination Survey (NHANES). Participants were categorized based on sex-specific deciles of the Metabolic Score for Insulin Resistance (METS-IR). Kaplan–Meier survival analysis and Cox proportional hazards models were used to assess the association between METS-IR and all-cause mortality. Restricted cubic spline (RCS) modeling explored potential non-linear relationships.</p> Results <p>Marked sex-related disparities were identified in clinical and metabolic characteristics. Elevated METS-IR significantly predicted increased all-cause mortality in females with MASLD (log-rank p &lt; 0.001), whereas this trend was not evident in males (p = 0.54). Multivariable Cox models showed that higher METS-IR independently correlated with mortality in women with MASLD and advanced fibrosis, but not in their male counterparts.</p> Conclusion <p>The prognostic significance of METS-IR differs by sex in MASLD. Elevated METS-IR independently increases long-term mortality risk in females, supporting the need for sex-specific risk evaluation in managing metabolic liver disease.</p>

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Sex-specific differences in the prognostic value of METS-IR for long-term outcomes in patients with MASLD and advanced liver fibrosis: a nationwide study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月31日

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  • Binbin Song,
  • Yuan Zhou,
  • Rui Su,
  • Yan Wang,
  • Song Chen,
  • Wenjin Chen

摘要

Objective

Insulin resistance (IR) plays a critical role in shaping long-term outcomes in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Recent findings suggest that biological sex may influence the onset and progression of MASLD, yet it remains unclear whether sex modifies the link between IR and mortality in those with MASLD and advanced liver fibrosis.

Methods

We analyzed data from 14,081 MASLD patients (7327 men and 6754 women) drawn from the 2001–2018 cycles of the National Health and Nutrition Examination Survey (NHANES). Participants were categorized based on sex-specific deciles of the Metabolic Score for Insulin Resistance (METS-IR). Kaplan–Meier survival analysis and Cox proportional hazards models were used to assess the association between METS-IR and all-cause mortality. Restricted cubic spline (RCS) modeling explored potential non-linear relationships.

Results

Marked sex-related disparities were identified in clinical and metabolic characteristics. Elevated METS-IR significantly predicted increased all-cause mortality in females with MASLD (log-rank p < 0.001), whereas this trend was not evident in males (p = 0.54). Multivariable Cox models showed that higher METS-IR independently correlated with mortality in women with MASLD and advanced fibrosis, but not in their male counterparts.

Conclusion

The prognostic significance of METS-IR differs by sex in MASLD. Elevated METS-IR independently increases long-term mortality risk in females, supporting the need for sex-specific risk evaluation in managing metabolic liver disease.