A natural history study of paediatric non-alcoholic fatty liver disease over 10 years

Laura Draijer; Maaike Voorhoeve; Marian Troelstra; Adriaan Holleboom; Ulrich Beuers; Meeike Kusters; Aart Nederveen; Marc Benninga; Bart Koot

doi:10.1016/j.jhepr.2023.100685

A natural history study of paediatric non-alcoholic fatty liver disease over 10 years

JHEP Rep. 2023 Jan 25;5(5):100685. doi: 10.1016/j.jhepr.2023.100685. eCollection 2023 May.

Authors

Laura Draijer^{1

2

3}, Maaike Voorhoeve¹, Marian Troelstra⁴, Adriaan Holleboom⁵, Ulrich Beuers⁶, Meeike Kusters⁷, Aart Nederveen⁴, Marc Benninga¹, Bart Koot¹

Affiliations

¹ Department of Pediatric Gastroenterology and Nutrition, Amsterdam University Medical Centers, Location Academic Medical Center/Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands.
² Amsterdam Reproduction & Development Research Institute, Amsterdam University Medical Centers, Location Academic Medical Center/Emma Children's Hospital, Amsterdam, the Netherlands.
³ Amsterdam UMC, University of Amsterdam, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, the Netherlands.
⁴ Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
⁵ Department of Vascular Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, the Netherlands.
⁶ Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
⁷ Department of Pediatrics, Amsterdam University Medical Centers, Location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Abstract

Background & aims: The long-term outcome of paediatric non-alcoholic fatty liver disease (NAFLD) has not been well established. Between 2008 and 2012, an unselected cohort of 133 children with severe obesity was screened for NAFLD. The aim of this study was to determine the 10-year natural history of NAFLD in this cohort.

Methods: All 133 participants of the original study were approached. Proton magnetic resonance spectroscopy (¹H-MRS) and the Enhanced Liver Fibrosis® (ELF) test were used to assess longitudinal changes in steatosis and fibrosis, respectively. Risk factors for disease progression were explored.

Results: Fifty-one of the 133 participants (38%) from the original cohort were included. The mean follow-up time was 10.3 years (range 7-13 years), 65% were female and 92% had persistent obesity. The proportion of participants with steatosis remained unchanged (47%). Nine individuals developed steatosis and in nine individuals steatosis resolved. Predefined relevant individual changes in ¹H-MRS were seen in 38% of the participants. The mean ELF test did not change significantly (8.70 ± 0.58 vs. 8.51 ± 0.71, p = 0.22). However, 16% had a relevant increase in ELF test and 6% of those with NAFLD developed advanced fibrosis at follow-up. Changes in steatosis correlated with changes in established metabolic risk factors, alanine aminotransferase, and bariatric surgery. A change in the ELF test was associated with a change in triglycerides.

Conclusions: This 10-year follow-up study shows that one-third of the young adults who had childhood obesity develop steatosis and in one-third steatosis resolves. Six percent of those with NAFLD had developed advanced fibrosis at follow-up. These data underscore the importance of screening for NAFLD and monitoring for progression to advanced NAFLD in young people with obesity.

Impact and implications: Childhood obesity accompanied by fat accumulation in the liver persists into young adulthood in the vast majority, and 6% develop serious liver injury. Worsening of metabolic disturbances increases the risk of liver injury.

Keywords: Children; Fibrosis; Hepatic steatosis; Outcomes; Progression.