Accelerometer-based sedentary time and physical activity with MASLD and liver cirrhosis in 2684 British adolescents

Among adolescents, steatotic liver disease (SLD) or metabolic dysfunction-associated SLD (MASLD) is the most prevalent (7.6%) chronic liver disease globally and the prevalence could increase fivefold in populations with obesity. The infiltration of at least 5% of hepatocytes without significant alcohol consumption may lead to MASLD, which could progress to cirrhosis and hepatocellular carcinoma. One in five young adults had steatosis and 2.5% had liver fibrosis around the age of 24 years, thus, the primordial and primary prevention of liver diseases is of public health and clinical significance. Recent long-term longitudinal studies have shown that increasing physical activity (PA) and reducing sedentary time (ST) may lower the risk of fat mass obesity, dyslipidaemia, insulin resistance, inflammation and vascular stiffness among children, adolescents, and young adults. In clinical trials, PA has been associated with a reduced risk of MASLD among adults, and a longitudinal study of 50-year-old adults reported that self-reported vigorous PA but not moderate PA was associated with reduced risk of MASLD. However, studies on long-term patterns of accelerometer-based movement behaviours (ST, LPA, MVPA) in relation to MASLD and liver fibrosis in the young population are lacking. Evidence suggests that triglycerides and inflammation are higher in adolescents and young adults with MASLD, MASLD prevalence worsens with obesity, and smoking, socioeconomic status and alcohol intake were not associated with MASLD. Higher liver enzyme concentrations (ALT, AST, GGT) have been positively associated with liver fibrosis in the presence of MASLD in youth. Since children and adolescents accumulate more time engaging in LPA than MVPA, identifying long-term lifestyle strategies is an urgent priority. The present study examined: (1) longitudinal associations of objectively measured ST, LPA and MVPA from ages 11 to 24 years with the risk of MASLD and liver fibrosis in adolescents (17 years) and young adults (24 years) measured with transient elastography; and (2) mediating effects of triglycerides, inflammation, fat mass and lean mass on the relationships of movement behaviour with MASLD, liver fibrosis, and liver enzymes from ages 17 to 24 years, using ALSPAC data.

Prior evidence indicates PA can reduce hepatic fat and improve liver enzymes in youth in short-term trials, while observational studies in adults suggest vigorous PA may lower MASLD risk. Cross-sectional studies in adults from the Netherlands and Japan reported no association between accelerometer-measured ST and ultrasound-assessed steatosis after adjustment. Emerging longitudinal youth studies show that higher PA and lower ST relate to favorable cardiometabolic profiles (less fat mass, better lipids, reduced inflammation, lower vascular stiffness). In adolescents and young adults, triglycerides and inflammation are elevated in MASLD, obesity markedly increases prevalence, and higher ALT, AST, and GGT are associated with fibrosis, but the mediating roles of these factors in movement–liver relationships were unclear prior to this study.

Design and cohort: Prospective longitudinal analysis within the ALSPAC UK birth cohort. Eligible participants (n=2684; 57% female) had at least one accelerometer assessment of sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) at ages 11, 15, or 24 years and complete liver steatosis and fibrosis measures at age 24 years. Ethics approvals were obtained; informed consent was provided. Movement behaviour: At ages 11 and 15 years, participants wore an MTI ActiGraph AM7164 accelerometer for 7 days; at 24 years, an ActiGraph GT3X+ was worn for four consecutive days. Devices were worn on the waist during waking hours. Valid data required ≥10 h/day on ≥3 days (≥2 weekdays and ≥1 weekend day). Data were processed into 60 s epochs using Kinesoft per established protocols. Cutpoints: at 11/15 years, ST 0–<100 cpm, LPA 100–2296 cpm, MVPA >2296 cpm; at 24 years, ST 0–<100 cpm, LPA 100–2020 cpm, MVPA >2020 cpm (Evenson-derived youth thresholds). Liver outcomes: At 24 years, transient elastography (FibroScan 502 Touch) provided liver stiffness (kPa; fibrosis staging F0–F4 using MASH-related METAVIR cutoffs: F0–F1 <7.9 kPa; F2 7.9–<8.8; F3 8.8–<11.7; F4 ≥11.7 kPa [cirrhosis]) and controlled attenuation parameter (CAP; dB/m) for steatosis grading S0 <248; S1 248–<268; S2 268–<280; S3 ≥280. Ten valid readings were required. At 17 years, ultrasound assessed presence of steatosis (echogenicity) and acoustic radiation force impulse imaging measured liver stiffness (shear velocity m/s); advanced stiffness defined as ≥2.25 m/s. Harmful drinkers were excluded from ultrasound analyses. Laboratory and covariates: Fasting ALT, AST, and GGT were assayed at ages 17 and 24 in a single lab. Additional measures at 17 and 24 included height, weight, BMI, DXA total fat mass and lean mass, blood pressure (Omron 705-IT), heart rate, fasting lipids, glucose, insulin (HOMA-IR), high-sensitivity C-reactive protein, smoking status (past 30 days), family medical history (hypertension, diabetes, high cholesterol, vascular disease), and maternal socioeconomic status. Statistical analysis: Descriptive statistics compared sexes. Generalized linear mixed-effect models estimated associations of cumulative 4-year (11–15) ST/LPA/MVPA with advanced liver stiffness and steatosis at 17 years, and cumulative 13-year (11–24) ST/LPA/MVPA with cirrhosis (F4) and severe steatosis (S3) at 24 years. Model 1 unadjusted; Model 2 adjusted for sex; family history; socioeconomic status; time-varying age, LDL-C, insulin, triglycerides, hs-CRP, HDL-C, heart rate, systolic blood pressure, glucose, fat mass, lean mass, smoking; and mutual adjustment for other movement behaviours. Skewed covariates were log-transformed; multiple imputations addressed missingness; Sidak correction applied. Sensitivity analysis used severe steatosis cutpoint ≥275 dB/m. Mediation analyses used structural equation models with 1000 bootstraps to test indirect (mediation) or suppression effects of cumulative triglycerides, hs-CRP, HOMA-IR, fat mass, and lean mass on associations of cumulative ST/LPA/MVPA with 24-year liver indices and 17–24-year enzyme changes; mediation quantified via differences between total and direct effects; significance at two-sided p<0.05.

- Sample: 2684 participants (mean baseline age 11.75 years; 57.3% female). Steatosis prevalence increased from 2.6% at 17 years to 20.5% at 24 years (~8-fold). ST rose from ~6 h/day in childhood to ~9 h/day in young adulthood; LPA declined from ~6 h/day to ~3 h/day; MVPA showed a U-shaped pattern. - Age 17 outcomes (cumulative 11–15 years): Higher ST associated with greater odds of advanced liver stiffness (Model 2 OR per 1 min/day increase ≈1.001; p<0.001) and lower odds of steatosis after adjustment (OR 0.998 [0.997–0.998]; p<0.0001). Higher LPA associated with lower odds of advanced stiffness (adjusted OR 0.999; p=0.049) and steatosis (0.998; p<0.001). Higher MVPA associated with lower odds of advanced stiffness (adjusted OR 0.999; p=0.033) and steatosis (0.994; p<0.001). - Age 24 outcomes (cumulative 11–24 years): ST associated with higher odds of cirrhosis unadjusted (OR 1.004 [1.002–1.005]; p=0.001) but not after full adjustment; ST associated with higher odds of severe steatosis (unadjusted OR 1.001 [1.001–1.002]; p=0.002; adjusted OR 1.001 [1.000–1.001]; p=0.027). LPA associated with lower odds of cirrhosis (adjusted OR 0.989 [0.987–0.991]; p<0.0001); association with severe steatosis was not significant after full adjustment. MVPA not associated with cirrhosis (adjusted OR 1.005 [0.994–1.015]; p=0.387) but associated with lower odds of severe steatosis (adjusted OR 0.997 [0.995–0.999]; p=0.002). - Sensitivity (severe steatosis ≥275 dB/m): ST increased risk (OR 1.001 [1.001–1.002]; p<0.001); LPA reduced risk (OR 0.996 [0.996–0.997]; p<0.001); MVPA not significant (OR 1.000 [0.999–1.002]; p=0.528) after full adjustment. - Liver enzymes (17–24 years): Increased cumulative ST was directly associated with progressively higher ALT, AST, and GGT. Cumulative LPA associated with decreased ALT and AST and lower GGT. Cumulative MVPA associated with decreased ALT, AST, and GGT overall, with effects variably suppressed by body composition. - Mediation/suppression: For ST, lean mass partially mediated lower CAP (33.3% mediation) and partially suppressed enzyme increases (up to 22.9%); fat mass suppressed associations with fibrosis and steatosis (18.2–28.4% suppression) and minimally mediated ALT/AST increases (≤6.7%); hs-CRP mediated associations with fibrosis and CAP (13.3–15.5% mediation). For LPA, fat mass mediated 7.1–16.7% of associations with lower fibrosis/higher CAP and GGT; lean mass mediated 1.6–2.2% of ALT/AST decreases; hs-CRP mediated 2.8–5.9% of ALT/AST decreases. For MVPA, fat mass suppressed beneficial effects on steatosis and enzymes (41.4–63.6% suppression); lean mass mediated higher fibrosis score (66.7% mediation) and suppressed beneficial effects on steatosis and enzymes (20.6–35.3%); hs-CRP mediated increases in AST/GGT (~42.9%); triglycerides mediated 29% of ALT decrease. - Estimated practical impact: Sustaining 3–4 h/day of LPA from childhood may prevent ~11 per 1000 cases of cirrhosis and ~4 per 1000 cases of severe steatosis by young adulthood; ~50 min/day of MVPA may prevent ~3 per 1000 cases of severe steatosis.

This study addresses a key evidence gap by linking device-measured movement behaviours across 13 years of growth with objective liver health indices in youth. Cumulative sedentary time was consistently related to higher odds of advanced stiffness/cirrhosis and severe steatosis and to worsening liver enzymes, suggesting sustained ST contributes to adverse hepatic remodeling and injury. In contrast, cumulative LPA was associated with reduced risk of advanced stiffness in adolescence and cirrhosis in young adulthood and with more favorable liver enzymes, underscoring LPA as a potent, feasible target given youths’ greater time in LPA than MVPA. MVPA robustly related to lower steatosis risk (adolescence and severe steatosis at 24 years) but not to cirrhosis, indicating intensity-specific benefits. Mediation analyses reveal that body composition and inflammation partly explain or suppress these associations: fat mass often suppressed the protective effects of MVPA on steatosis and enzymes, while lean mass mediated a paradoxical association between MVPA and higher fibrosis score—likely reflecting physiological adaptations rather than pathological cirrhosis, consistent with no increased cirrhosis risk. Inflammation (hs-CRP) partly mediated the ST–liver relationships. Collectively, the findings suggest that reducing ST while increasing LPA and sustaining MVPA from childhood could meaningfully mitigate early liver disease trajectories, with body composition management enhancing benefits.

Liver steatosis prevalence increased about eightfold from adolescence to young adulthood in this cohort. Decreasing sedentary time and increasing both light and moderate-to-vigorous physical activity from childhood independently attenuate the risks of severe steatosis and cirrhosis and improve liver enzymes. Maintaining at least 3–4 h/day of LPA could prevent approximately 11 per 1000 cases of cirrhosis and 4 per 1000 cases of severe steatosis by early adulthood, and achieving about 50 min/day of MVPA could prevent ~3 per 1000 cases of severe steatosis. Future research should include repeated transient elastography across adolescence and young adulthood to clarify temporal dynamics, incorporate sleep and detailed dietary/alcohol intake data, and evaluate interventions targeting reductions in ST alongside increases in LPA and MVPA with concurrent body composition management.

- No liver biopsy (gold standard); transient elastography and ultrasound used instead, though recommended and validated. - Different liver assessment modalities at 17 (ultrasound/ARFI) vs 24 years (transient elastography) precluded direct progression analyses and may introduce measurement heterogeneity. - Potential residual confounding from unmeasured sleep duration, detailed dietary intake, and grams of alcohol consumed. - Accelerometers worn for 7 days (11/15 years) and 4 days (24 years) may not fully capture habitual behavior; possible Hawthorne effect. - Different ActiGraph models used across time points could introduce bias despite high agreement; differing cutpoints applied to mitigate variability. - Predominantly Caucasian cohort limits generalizability to other ethnicities.