Commentary: Of women, liver, and heart

Abstract

This commentary is devoted to a recent study by Ren and Zheng (Nutr Metab Cardiovasc Dis. 2023;33:1349-1357). These authors analyzed sex-stratified long-term outcomes relevant to all-cause and cardiovascular field outcomes among 2,627 nonalcoholic fatty liver disease (NAFLD) adults enrolled in the 2000-2014 National Health and Nutrition Examination Surveys and identified with United States Fatty Liver Index (US FLI) score. Data have shown that, compared to women, men were exposed to a significantly higher all-cause mortality and the maximal risk was seen among those who had obesity and type 2 diabetes. However, women aged ≤ 60 years had a higher risk of death owing to cardiovascular disease (CVD). Conversely, no significantly increased risk of death from CVD was observed among women over 60 years compared to men of the same age group. The study by Ren and Zheng further fosters our understanding of cardiometabolic risk factors, illustrating sex differences present in NAFLD. The distinct impact of NAFLD on CVD by sex and age suggests that cardiometabolic comorbidities may be particularly underestimated among young and middle-aged women with NAFLD. The research by Ren and Zhang may stimulate future investigations exploring the molecular and cellular grounds underlying these findings, notably including the role of fibrosing NAFLD as a strong risk modifier of CVD. In conclusion, an improved understanding of sex-specific regulation of human metabolism in the liver and other key metabolic organs is a research priority finalized for implementing precision medicine approaches in NAFLD arena.