8450 Accelerometer-based Sedentary Time and Physical Activity with the Risk of Severe Liver Steatosis and Liver Cirrhosis in 2684 Children: A 13-Year Longitudinal and Mediation Study

Abstract Disclosure: A.O. Agbaje: None. Background: Non-alcoholic fatty liver diseases have been associated with physical inactivity in adults. However, long-term evidence on the prospective relationship of accelerometer-measured sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous PA (MVPA) with liver steatosis and fibrosis and changes in liver enzymes in a large paediatric population is scarce. Hypothesis: It was hypothesized that increased ST from childhood through young adulthood would increase the risk of severe liver steatosis and cirrhosis and worsen liver enzymes, whereas engaging in LPA and MVPA would reduce the risk. Methods: From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 2684 children aged 11 years who had at least one follow-up time-point accelerometer-measured ST, LPA, and MVPA over a period of 13 years, and liver indices and enzymes measures at age 24 years clinic visit were included. Liver steatosis and fibrosis were assessed by transient elastography (FibroScan 502 Touch) and categorized as fibrosis stage F0-F4 and steatosis grade (S0-S3) at age 24 years. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (GGT) were assayed at ages 17 and 24 years. Longitudinal associations were examined using generalized linear mixed-effect models, while mediation analyses were conducted with structural equation models. Results: Among 2684 children (mean [SD] age, 11.75 [0.24] years; 1537 [57.3%] females]), ST increased from 6 hours/day in childhood to 9 hours/day in young adulthood, while LPA decreased from 6 hours/day to 3 hours/day and MVPA was relatively stable at 50 minutes/day. The prevalence of liver cirrhosis [F4, ≥11·7 kPa] and severe liver steatosis [S3, controlled attenuation parameter value ≥280 dB/m] is 0.3 and 10%, respectively. Cumulative 1-minute/day increase in ST from ages 11-24 years was associated with higher odds of liver cirrhosis (odds ratio 1.004 [95% CI 1.002 - 1.005] p<0.001) and severe liver steatosis (1.001 [1.001 - 1.002] p=0.002) at age 24 years. Increased ST from childhood was directly associated with increased ALT, AST, and GGT from ages 17 - 24 years. Cumulative 1-minute/day LPA was associated with lower odds of liver cirrhosis (0.990 [0.990 - 0.991] p<0.001) and severe liver steatosis (0.999 [0.998 - 0.999] p<0.001) at age 24 years, as well as decreased liver enzymes. Cumulative 1-minute/day MVPA was associated with associated with lower odds of severe liver steatosis (0.996 [0.994 - 0.998] p<0.001) but not liver cirrhosis at age 24 years. MVPA effect on lowering liver steatosis was significantly suppressed (64% suppression) by increased fat mass. Conclusions: Increasing LPA, sustaining MVPA, and decreasing ST from childhood may independently attenuate and reverse the risk of severe liver steatosis and cirrhosis by young adulthood. Presentation: 6/1/2024