Childhood Underweight and Adulthood Obesity Associated With Increased Risk of MASLD and Cirrhosis: A Prospective Cohort Study of 375,125 Adults.

Abstract

Background: Obesity is a known risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD) and cirrhosis, but the long-term effects of childhood thinness and body size changes across life are unclear. We aimed to assess how body size and child-to-adult body size trajectories relate to major liver outcomes.

Methods: We studied 375,125 UK Biobank participants without liver disease at baseline. Childhood body size (thinner, average, and plumper) and adulthood body size (normal, overweight, and obesity) were combined into nine trajectories. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MASLD and cirrhosis. Kaplan-Meier survival curves assessed the association between body size trajectories and liver diseases. Sensitivity and subgroup analyses tested robustness.

Results: Compared with average childhood body size, childhood thinness was associated with higher risks of MASLD (HR 1.18, 95% CI 1.11-1.27) and cirrhosis (HR 1.15, 95% CI 1.03-1.27). Relative to persistently normal body size, the "thinner to obesity" trajectory showed the greatest risks of MASLD (HR 3.95, 95% CI 3.29-4.76) and cirrhosis (HR 3.97, 95% CI 3.30-4.77). The "plumper to normal" trajectory was not associated with increased MASLD or cirrhosis.

Conclusion: Childhood thinness is associated with increased risks of MASLD and cirrhosis in adulthood. Achieving a normal BMI in adulthood may mitigate liver-related risks linked to childhood overweight.