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The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years
  1. A E Feldstein1,
  2. P Charatcharoenwitthaya2,
  3. S Treeprasertsuk2,
  4. J T Benson3,
  5. F B Enders3,
  6. P Angulo2
  1. 1
    Department of Pediatric and Adolescent Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
  2. 2
    Department of Internal Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
  3. 3
    Department of Health Sciences Research, Division of Biostatistics, Mayo Clinic, Rochester, Minnesota, USA
  1. Correspondence to Dr P Angulo, Division of Digestive Diseases and Nutrition, University of Kentucky, 800 Rose Street, Rm MN469, Lexington, KY 40536, USA; paul.angelo{at}


Objectives: The long-term prognosis of non-alcoholic fatty liver disease (NAFLD) in children remains uncertain. We aimed at determining the long-term outcomes and survival of children with NAFLD.

Design: Retrospective longitudinal hospital-based cohort study.

Patients: Sixty-six children with NAFLD (mean age 13.9 (SD 3.9) years) were followed up for up to 20 years with a total of 409.6 person-years of follow-up.

Results: The metabolic syndrome was present in 19 (29%) children at the time of NAFLD diagnosis with 55 (83%) presenting with at least one feature of the metabolic syndrome including obesity, hypertension, dyslipidaemia and/or hyperglycaemia. Four children with baseline normal fasting glucose developed type 2 diabetes 4–11 years after NAFLD diagnosis. A total of 13 liver biopsies were obtained from five patients over a mean of 41.4 (SD 28.8) months showing progression of fibrosis stage in four children. During follow-up, two children died and two underwent liver transplantation for decompensated cirrhosis. The observed survival free of liver transplantation was significantly shorter in the NAFLD cohort as compared to the expected survival in the general United States population of the same age and sex (log-rank test, p<0.00001), with a standardised mortality ratio of 13.6 (95% confidence interval, 3.8 to 34.8). NAFLD recurred in the allograft in the two cases transplanted, with one patient progressing to cirrhosis and requiring re-transplantation.

Conclusions: Children with NAFLD may develop end-stage liver disease with the consequent need for liver transplantation. NAFLD in children seen in a tertiary care centre may be associated with a significantly shorter survival as compared to the general population.

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  • Funding PC was supported by a grant from the Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. ST was supported by a medical research scholarship from the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

  • Competing interests None.

  • Provenance and Peer review Not commissioned; externally peer reviewed

  • See Commentary, p 1442

  • Ethics approval The study was approved by the Mayo Institutional Review Board on 18 June 2002.

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