NAFLD Increases Mortality in Children and Young Adults Over the Long Term

A long-term Swedish study found that nonalcoholic fatty liver disease (NALFD) significantly increased mortality in children and young adults, particularly due to cancer, cardiometabolic disease, and liver disease.

Children and young adults with nonalcoholic fatty liver disease (NALFD) have significantly higher mortality compared with the general population. According to the study published in Journal of Hepatology, the excess mortality was primarily from cancer, cardiometabolic disease, and liver disease.

Researchers evaluated a nationwide cohort of pediatric and young adult patients in Sweden with biopsy-confirmed NAFLD and compared them with matched general population controls to analyze overall and cause-specific mortality based on the presence and severity of NAFLD.

While there have been studies on NAFLD in adults, there is little known “about the long-term prognosis and histological correlates of survival” in children and young adults with NAFLD, the authors explained. They noted that 7.6% of the general pediatric population worldwide and more than 30% of children with obesity have NAFLD.

Children who are diagnosed with NAFLD may already have fibrosis, and a rapid progression to nonalcoholic steatohepatitis (NASH), a severe form of NAFLD.

The study included 718 children and young adults with NAFLD. Among these individuals, 446 (62.1%) had simple steatosis and 272 (37.9%) had NASH. Less than half (44%) were diagnosed younger than age 18. Compared with the control population (n = 3457), the patients with NAFLD were more likely to have cardiovascular disease (1.4% vs 6.8%), diabetes (0.3% vs 5.6%), and other metabolic comorbidities (0.5% vs 13.6%).

During the follow-up period (median 15.8 years for NAFLD patients and 16.9 years for controls), 59 patients with NAFLD died for a mortality rate of 5.5/1000 person-years compared with 36 deaths among the controls for a mortality rate of 0.65/1000 person-years. The absolute risk of overall mortality over 20 years was 7.7% for the NAFLD cohort and 1.1% for the controls, “which translated to 1 additional death per every 15 patients with NAFLD, followed for 20 years,” the authors wrote.

As NAFLD severity increased, so did the risk of overall mortality. Patients with simple steatosis had a 20-year absolute risk of mortality that was 5.7% higher than controls and patients with NASH had a 20-year absolute risk of mortality that was 8.4% higher.

Patients with NAFLD, compared with controls, had increased mortality due to:

  • Cancer (1.67 vs 0.07/1000 person-years)
  • Cardiometabolic disease (1.12 vs 0.14/1000 person-years)
  • Liver disease (0.93 vs 0.04/1000 person-years)
  • Other/exogenous causes (1.8 vs 0.4/1000 person-years)

Among the limitations of the study, the authors noted that since it was a retrospective study of children and young adults who underwent biopsy, there could be a selection bias. In addition, since the Swedish population is primarily White and has a low prevalence of pediatric obesity, additional studies with larger, diverse populations are needed.

“…our findings underscore the need for improved prevention, risk stratification and surveillance strategies to improve long-term outcomes for this growing patient population,” the authors concluded.

Reference

Simon TG, Roelstraete B, Hartjes K, et al. Non-alcoholic fatty liver disease in children and young adults is associated with increased long-term mortality. J Hepatol. Published online July 2, 2021. doi:10.1016/j.jhep.2021.06.034