Nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) are prevalent chronic liver diseases, particularly among adolescents and young adults. The global prevalence of MASLD is significant (7.6%), with a potential fivefold increase in obese populations. MASLD can progress to cirrhosis and hepatocellular carcinoma. While increasing physical activity (PA) and reducing sedentary time (ST) have shown promise in reducing the risk of various health issues, including MASLD in adults, longitudinal studies examining accelerometer-based movement behaviors (ST, LPA, and MVPA) in relation to MASLD and liver fibrosis in young populations are limited. This study aims to investigate the longitudinal associations of objectively measured ST, LPA, and MVPA from ages 11 to 24 years with the risk of MASLD and liver fibrosis, considering mediating factors like triglycerides, inflammation, fat mass, and lean mass. The Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort provided the data for this analysis. The study's significance lies in addressing the urgent need for understanding lifestyle interventions to lower the risk of MASLD, particularly considering that children and adolescents spend more time in LPA than MVPA.

Existing research highlights the increasing prevalence of NAFLD and MASLD among young adults. Studies indicate that higher triglycerides and inflammation are associated with MASLD in this population, often exacerbated by obesity. Elevated liver enzyme concentrations (ALT, AST, GGT) are linked to liver fibrosis in the presence of MASLD in youth. However, the interplay between movement behaviors (ST, LPA, MVPA) and MASLD, along with the mediating role of metabolic factors, remains unclear. While some studies suggest a link between increased PA and reduced risk of MASLD in adults, longitudinal data using accelerometer-based measurements in young populations are lacking. The current study fills this gap by utilizing objective measures of movement behavior to investigate the long-term impact on liver health.

This longitudinal cohort study utilized data from the ALSPAC, a UK birth cohort. 2684 participants (57% female) with at least one accelerometer-measured ST, LPA, and MVPA data point between ages 11 and 24 and complete liver assessments at age 24 were included. Accelerometer data (Actigraph AM7164 and GT3X+) were collected during 7-day (ages 11 and 15) and 4-day (age 24) periods. Validated cutpoints were used to categorize ST, LPA, and MVPA. Liver steatosis and fibrosis were assessed using transient elastography (age 24) and ultrasonography (age 17). Liver enzymes (ALT, AST, GGT) were measured at ages 17 and 24. Generalized linear mixed-effect models examined longitudinal associations of cumulative ST, LPA, and MVPA with liver cirrhosis and severe steatosis. Mediation analyses using structural equation models explored the mediating effects of triglycerides, inflammation (high-sensitivity C-reactive protein), fat mass, lean mass, and insulin resistance. Adjustments were made for various covariates, including demographics, lifestyle factors, and cardiometabolic parameters. Multiple imputations handled missing data. Sensitivity analyses were conducted using alternative cut-off points for severe liver steatosis.

The prevalence of liver steatosis increased eightfold from age 17 to 24. Males had higher fat mass, ST, and advanced liver steatosis. A 1-min/day increase in cumulative ST (ages 11–24) was associated with higher odds of liver cirrhosis and severe steatosis. Conversely, increased cumulative LPA (ages 11–24) was associated with lower odds of liver cirrhosis and severe steatosis. Cumulative MVPA (ages 11–24) was linked to lower odds of severe steatosis but not cirrhosis. Increased lean mass partially mediated the association between increased ST and lower liver steatosis. Increased fat mass suppressed the association between increased ST and higher liver fibrosis and lower liver steatosis. Increased fat mass partially mediated the association between cumulative LPA and higher liver steatosis, while increased lean mass partially mediated the association between LPA and decreased liver enzymes. Increased fat mass suppressed the association between cumulative MVPA and lower steatosis. MVPA's effect on lowering liver steatosis was significantly suppressed (64%) by increased fat mass.

This study provides strong evidence for the independent associations of movement behaviors with liver health indicators in adolescents and young adults. The findings highlight the potential benefits of increasing LPA and MVPA and reducing ST in mitigating the risk of severe liver steatosis and cirrhosis. The mediating and suppressing roles of fat mass and lean mass emphasize the importance of body composition in the interplay between PA, ST, and liver health. The contrasting effects of LPA and MVPA on liver fibrosis suggest different mechanisms may be at play. Future research could explore the underlying mechanisms further, the role of specific types of PA, and develop more targeted interventions.

This large, longitudinal study demonstrates that increasing LPA and MVPA, and reducing ST during childhood and adolescence are independently associated with a reduced risk of severe liver steatosis and cirrhosis. The study highlights the importance of lifestyle interventions and the complex interplay between body composition, physical activity, and liver health. Future research should focus on more detailed mechanistic studies and explore the potential of tailored interventions targeting specific movement behaviors and body composition to prevent liver disease in young adults.

The study used transient elastography and ultrasonography, which are not as definitive as liver biopsies. The accelerometer data collection periods (7 and 4 days) might not fully capture habitual behaviors. The study population was predominantly Caucasian, limiting generalizability. Missing data on sleep, diet, and alcohol consumption could have introduced biases. Different accelerometer models and cutpoints used at different ages could also introduce some bias.