Cumulative Burden of Fatty Liver and Kidney Cancer in Young Men: A National Population-Based Study

<b>Background:</b> This national population-based study aimed to assess the cumulative burden of non-alcoholic fatty liver disease (NAFLD) measured via the fatty liver index (FLI) and its association with kidney cancer risk in young men aged 20-39. <b>Methods</b>: Using the Korean National Health Insurance Service database, we examined a cohort of 1,007,906 men (age 20-39) who underwent four consecutive annual check-ups from 2009 to 2012. The FLI, calculated from body mass index values, waist circumference, triglyceride levels, and gamma-glutamyl transferase levels, was used to quantify the cumulative burden of NAFLD (FLI ≥ 60). The study population was followed until a kidney cancer diagnosis was made, death occurred, or the advent of 2020. <b>Results:</b> Over a mean follow-up of 7.74 years, 649 subjects developed kidney cancer. An increasing mean FLI was associated with an elevated hazard ratio (HR) for kidney cancer. The cumulative frequency of NAFLD (0-4) showed a corresponding increase in the HR for kidney cancer. This association persisted after adjusting for lifestyle factors including smoking, alcohol consumption, and physical activity. Subjects with improved NAFLD had a decreased risk of kidney cancer compared to those with persistent or aggravated NAFLD. <b>Conclusions:</b> This study revealed a significant association between NAFLD and kidney cancer in young men. Addressing NAFLD may offer a valuable opportunity to mitigate premature morbidity and mortality associated with young-onset kidney cancer in subsequent generations.