Improvement in liver histology is associated with reduction in dyslipidemia in children with nonalcoholic fatty liver disease

J Pediatr Gastroenterol Nutr. 2015 Mar;60(3):360-7. doi: 10.1097/MPG.0000000000000584.

Abstract

Objectives: Nonalcoholic fatty liver disease (NAFLD), the most common cause of liver disease among US children, may be associated with cardiovascular disease (CVD) risk. The present study sought to determine the prevalence of dyslipidemia in children with NAFLD and assess dyslipidemia by liver histology and histologic changes.

Methods: Individuals in the Treatment of NAFLD in Children (TONIC) trial were included (N = 173). In the TONIC trial, children with NAFLD were randomized to vitamin E, metformin, or placebo for 96 weeks. Nonalcoholic steatohepatitis (NASH) improved in 56 children. Change in lipid levels from baseline and 96 weeks was compared between patients with and without histologic improvement and with and without NASH.

Results: Dyslipidemia was frequent, with low high-density lipoprotein (HDL) (< 40 mg/dL) in 61.8%, hypertriglyceridemia (≥ 130 mg/dL) in 50.3%, hypercholesterolemia (≥ 200 mg/dL) in 23.7%, elevated low-density lipoprotein (LDL) (≥ 130 mg/dL) in 21.5%, elevated non-HDL cholesterol (non-HDL-C) (≥ 145 mg/dL) in 35.2%, and triglycerides/HDL > 3.0 in 57.2% of patients. Histologic improvement was associated with significant decreases in cholesterol (-11.4 mg/dL vs -1.9 mg/dL, P = 0.04), LDL (-11.2 mg/dL vs -2.1 mg/dL, P = 0.04), and non-HDL-C (-8.8 mg/dL vs 0.5 mg/dL, P = 0.03) compared with those without improvement. Children with NASH resolution had significant decreases in cholesterol (-10.0 mg/dL vs -0.9 mg/dL, P = 0.02) and non-HDL-C (-7.3 mg/dL vs 1.1 mg/dL, P = 0.01) compared with those without NASH resolution. There was no improvement in triglycerides, HDL level, or triglycerides/HDL ratio in either group.

Conclusions: Dyslipidemia is frequent in children with NAFLD. NASH resolution and histologic improvement are associated with improvements in some forms of dyslipidemia.

Trial registration: ClinicalTrials.gov NCT00063635.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • Biopsy
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control
  • Child
  • Cohort Studies
  • Combined Modality Therapy
  • Double-Blind Method
  • Dyslipidemias / epidemiology
  • Dyslipidemias / etiology
  • Dyslipidemias / prevention & control*
  • Female
  • Humans
  • Liver / pathology*
  • Longitudinal Studies
  • Male
  • Non-alcoholic Fatty Liver Disease / blood
  • Non-alcoholic Fatty Liver Disease / pathology*
  • Non-alcoholic Fatty Liver Disease / physiopathology
  • Non-alcoholic Fatty Liver Disease / therapy
  • Prevalence
  • Remission Induction
  • Remission, Spontaneous
  • Risk Factors
  • United States / epidemiology

Substances

  • Biomarkers

Associated data

  • ClinicalTrials.gov/NCT00063635

Grant support