Nonalcoholic fatty liver disease in children and adolescents
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Nonalcoholic fatty liver disease in children and adolescents

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Nonalcoholic fatty liver disease in children and adolescents Nonalcoholic fatty liver disease in children and adolescents Presentation Transcript

  • Nonalcoholic Fatty Liver Disease in Children and Adolescents Peds GI Conference Joanna Yeh December 22, 2011
  • Goals • Basics and background of NAFLD. • Discuss who should be screened and then worked up for NAFLD and how. • Discuss recent JAMA article (April 2011) regarding treatment of NAFLD with vitamin E and metformin.
  • Background • NAFLD is the most common cause of chronic liver disease in children and adults. • In the U.S., ~30% of children and adolescents are overweight, ~15% are obese. • Adult data indicate 1/3 of patient with early NASH will have cirrhosis in 5-10 years. • Prevalence of NAFLD in children: ~10% overall (6 million), ~40% obese.
  • Cohen, et al, Human Fatty Liver Disease: Old Questions and New Insights, Science, June 2011.
  • Who should be screened? • Average age at diagnosis is 12 years. • Earliest reported case around 2 years. • More common in Hispanic Americans, then Asians and Whites compared to African Americans. • Hispanic adolescents more likely to develop significant liver fibrosis. • Boys more likely to have steatosis . • 10% of NAFLD cases are non-overweight. • Other risk factors? Genetics?
  • How should we screen? • AST/ALT • Ultrasound • MRI • Measurements for fibrosis. – PNFI: Pediatric NAFLD fibrosis index (age, waist circumference, TG level) – ELF: Enhanced liver fibrosis test (hyaluronic acid, aminoterminal propeptide of type 3 collagen, tissue inhibitor of metalloproteinase 1) – “Fibroscan” (transient elastography) • Gold standard for staging and grading is liver biopsy. • Who gets liver biopsy?
  • UCLA “Pediatric Obesity Clinical Decision Tool”
  • Cincinnati Children’s Protocol
  • Cincinnati Children’s Protocol
  • NASPGHAN Module
  • Beyond healthy lifestyle changes, no good therapeutic options available…
  • TONIC (Treatment of NAFLD in Children) Randomized Controlled Trial • Published in JAMA, April 2011. • Design: – Randomized, double-blind, double-dummy, placebo- controlled clinical trial – 10 university clinical research centers – 173 patients age 8-17 years with biopsy proven NAFLD between Sept 2005-March 2010 – Vitamin E 400 IU bid – Metformin 500 mg bid – Outcome: • Primary: sustained reduction in ALT (50% or less of baseline level or 40 U/L or less from 48-96 weeks after treatment • Secondary: histological improvements or resolution
  • Methods • Definition of NAFLD: liver biopsy with >5% steatosis. • Inclusions: NAFLD + “persistent elevation of serum ALT”. • Exclusions: diabetes mellitus or cirrhosis, less than 8 years old. • Liver biopsy at 96 weeks was done. • Why was primary outcome ALT improvement?
  • Figure 1. CONSORT Flow Diagram of TONIC Trial Participants Lavine, J. E. et al. JAMA 2011;305:1659-1668
  • Table 1. Baseline Characteristics by Treatment Group. Lavine, J. E. et al. JAMA 2011;305:1659-1668
  • Table 2. Primary Outcome: Sustained Reduction in ALT Level by Treatment Group. Lavine, J. E. et al. JAMA 2011;305:1659-1668
  • Table 3. Change From Baseline to End of Treatment in Liver Histology by Treatment Group. Lavine, J. E. et al. JAMA 2011;305:1659-1668
  • Article Conclusions • Neither vitamin E nor metformin was superior to placebo in attaining the primary outcome of sustained reduction in ALT level in patients with pediatric NAFLD. • Children treated with vitamin E showed improvements in terms of resolution of NASH in those with NASH or borderline NASH at baseline compared with placebo.
  • Critiques • Metformin dose adequate? No data provided on adherence/compliance. • Possible false negative due to under enrollment. • “Enrolling children with NAFLD but no requiring NASH may have limited the amount of improvement that could be achieved with treatment.” • How about children with NAFLD but lesser ALT elevations? • Secondary outcome analysis based on completers rather than intention to treat.
  • Take home points • ALT may not correlate well with disease. • Liver biopsy is required for NASH diagnosis. • Weight loss is currently the only long term solution. • Vitamin E may be appropriate for biopsy- proven NASH.
  • Many questions, no clear answers. No good guidelines.
  • References • Cohen, et al, Human Fatty Liver Disease: Old Questions and New Insights, Science June 2011. • Mencin and Lavine, Nonalcoholic Fatty Liver Disease in Children, Curr Opin Clin Nutr Metab Care, Mar 2011. • Barlow, Expert Committee Recommendations Regarding the Prevention, Assessment, and Treatment of Child and Adolescent Overweight and Obesity: Summary Report”, Pediatrics, 2007. • Schwimmer, et al, Prevalence of Fatty Liver in Children and Adolescents, Pediatrics, 2006. • Alkhouri, et al, A Combination of the Pediatric NAFLD Fibrosis Index and Enhanced Liver Fibrosis Test Identifies Children with Fibrosis, Clinical Gastro and Hepatology, Feb 2011. • Lavine, et al, Effect of Vitamin E or Metformin for Treatment of Nonalcoholic Fatty Liver Disease in Children and Adolescents, JAMA, April 2011.