The association between childhood obesity and major adverse liver outcomes in adolescence and young adulthood

Abstract

Background & aims: Paediatric obesity is associated with liver steatosis and injury. We aimed to investigate the association between paediatric obesity and the risk of major adverse liver outcomes (MALOs) during adolescence and adulthood.

Methods: A cohort study of children with overweight or obesity enrolled in the Swedish Childhood Obesity Treatment Register (1997-2020) was performed (n = 29,321). Controls from the general population matched by sex, birth year, and resident areas were obtained (n = 141,510). The individuals were followed from age 10 (or obesity treatment initiation) up to age 40. MALOs were defined as any occurrence of cirrhosis, hepatocellular carcinoma, oesophageal or gastric varices, portal hypertension, liver transplantation, ascites, liver failure, or liver-related mortality.

Results: During a median follow-up of 8.3 [Q1-Q3: 5.5-11.8] years, MALOs were identified in 77 individuals. The cumulative incidence of MALOs by age 40 was 1.14% in the obesity cohort and 0.52% in the control group. Childhood adiposity was associated with the risk of MALOs (hazard ratio 2.15, 95% CI 1.33-3.48, p = 0.002). Individuals who had childhood obesity and developed alcohol use disorder during follow-up had an even higher risk of MALOs than controls without alcohol use disorder (hazard ratio 7.64, 95% CI 2.73-21.47, p <0.001). Type 2 diabetes did not mediate the association between childhood obesity and MALOs (p = 0.54).

Conclusions: Paediatric obesity is associated with a two-fold increased risk of MALOs. However, the absolute risk of developing MALOs by age 40 remains low.

Impact and implications: Firstly, healthcare providers should recognise that the consequences of paediatric obesity are not limited to immediate health concerns but rather present a sustained consequence on liver health into adulthood. Secondly, our findings revealed that a substantial proportion of individuals with alcohol use disorder experienced onset during adolescence, significantly amplifying the risk of major adverse liver outcomes. This underscores the importance of incorporating routine assessment for alcohol use disorder within paediatric care, particularly during adolescence, to identify and mitigate this increased risk. Thirdly, while the incidence of major adverse liver outcomes up to age 40 remains low, we identify a population at increased risk. This could help to refine risk stratification and target interventions more effectively.

Keywords: alcohol use disorder; cirrhosis; liver failure; obesity; paediatric obesity; type 2 diabetes.

The figure illustrates the cumulative incidence of major adverse liver outcomes was higher in the obesity cohort than in the general population comparators, with a hazard ratio of 2.15 (95% CI: 1.33–3.48, p = 0.002).

Fig. 1

Cumulative incidence of MALOs between age 10 and 40 years in the obesity cohort and the general population comparators. Cumulative incidence in each group was estimated using a flexible parametric survival model. MALOs, major adverse liver outcomes.

Fig. 2

Joint effect between obesity and alcohol use disorder on the risk of MALOs. Hazard ratios were estimated using Cox regression. The reference group (hazard ratio = 1) was general population comparators without any diagnosis of alcohol use disorders. MALOs, major adverse liver outcomes.