New-Onset Age of Nonalcoholic Fatty Liver Disease and Cancer Risk

Abstract

Importance: The onset age of nonalcoholic fatty liver disease (NAFLD) is decreasing, and whether earlier ages of NAFLD onset are associated with increased cancer risk is currently unclear. Objective: To explore the association between NAFLD new-onset age and cancer risk. Design, Setting, and Participants: This cohort study was conducted among 179328 participants included in the Kailuan Cohort Study between 2006 and 2021. In total, 46100 incident NAFLD cases were identified. For each case, a participant matched by age (older or younger by 1 year) and sex was randomly selected to create a new matched study cohort. Data were analyzed from December 2022 through April 2023. Exposure: Onset of NAFLD. Main Outcomes and Measures: The association between the onset age of NAFLD and the risk of different cancer types was evaluated using weighted Cox regression models. Population-attributable fractions (PAFs) were used to quantify the association of NAFLD with cancer risk at different ages. Results: Among 63696 participants (mean [SD] age, 51.37 [12.43] years; 10932 females [17.2%] and 52764 males [82.8%]), 31848 individuals had NAFLD and 31848 individuals were in the control group. During a median (IQR) follow-up of 10.16 (7.89-11.67) years, 2415 patients were diagnosed with cancer. Compared with the matched group, patients aged less than 45 years at NAFLD onset exhibited a higher risk of cancer (average hazard ratio [AHR], 1.52; 95% CI, 1.09-2.12), and as the onset age of NAFLD increased, the cancer risk decreased (ages 45-54 years: AHR, 1.50; 95% CI, 1.15-1.97; ages 55-64 years: AHR, 1.13; 95% CI, 0.97-1.33; ages >65 years: AHR, 0.75; 95% CI, 0.45-1.27; P for interaction