The prognostic role of sex in non-alcoholic fatty liver disease (NAFLD)

INTRODUCTION: The global epidemic of non-alcoholic fatty liver disease (NAFLD) represents a significant public health issue with substantial healthcare implications. NAFLD has become the fastest-growing cause of orthotopic liver transplantation, driven by cases of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC).The variability in risk factors and treatment responses among individuals with NAFLD complicates the identification of those at high risk, as well as the development of tailored preventive and therapeutic strategies, hindering efforts to slow this escalating health crisis. The exploration of sex differences has emerged as an increasingly important focus in modern medicine. METHODS: A retrospective analysis was conducted using publicly available data from the “Non-alcohol Fatty Liver Disease” dataset on Kaggle. The dataset comprised 17,549 patients diagnosed with NAFLD. Survival outcomes were analyzed using Kaplan-Meier curves and Cox proportional hazards regression. Survival time was defined as the duration (in months) from diagnosis to death or the last follow-up. The primary outcome was overall survival, stratified by sex. The explanatory variables included sex (male = 1, female = 0) and other clinical covariates such as BMI and age. RESULTS: Kaplan-Meier analysis revealed a high overall survival rate at 5 years (>99%) for both sexes. However, males demonstrated a slightly lower survival probability compared to females. Cox proportional hazards regression indicated that being male was associated with a 20% higher risk of mortality (HR = 1.20, 95% CI: 1.08–1.33, p = 0.001 ). The likelihood ratio test confirmed the significance of sex as a predictor of survival in this population ( p = 0.001 ). Further stratification by BMI categories revealed no unexpected associations. CONCLUSION: In patients with NAFLD, male sex is associated with a higher risk of mortality compared to females, underscoring the potential influence of sex-related factors on disease progression and outcomes. These findings, derived from a publicly available dataset, emphasize the importance of full exploration of sex differences in NAFLD. Major research gap which must be addressed at all levels from basic science to clinical trials