Screening for NAFLD

As noted in previous blogs (see below), there is not a consensus with regard to screening for NAFLD in overweight and obese patients.  While some have argued for aggressive screening leading to an expensive tiered evaluation, other experts have been reluctant to endorse this approach, in part due to the magnitude of the problem and due to the perceived lack of therapeutic options.  Weighing in on this controversy is a new study (Aliment Pharm Ther 2013; DOI: 10.1111/apt.12518, link -from Jeff Schwimmer’s twitter feed:

In the study’s introduction, the prevalence of NAFLD, estimated to be 9.6% of all children aged 2-19 years, along with society guidelines are reviewed.

The authors examined information from the clinical evaluation of 347 children (>10 years) [overweight (7%)/obese (93%)] who were referred by their primary care physician due to either an elevated ALT or suspected NAFLD.  Referral was at the discretion of the primary care attending and not based on a specific ALT value.  Median age was 13.5 years and 64% were boys.

1st tier: Subsequently, all patients underwent hepatic panel, GGT, CBC/diff, and coagulation studies.  2nd tier: If abnormal, the next set of labs may have included any or all of the following: studies for hepatitis infection (HAV, HBV, HCV), HIV, alpha-1-antitrypsin, ANA, anti-smooth muscle antibody, anti-liver kidney microsomal antibody, quantitative IgG, ceruloplasmin,  24-h urinary copper, tissue transglutaminase antibody, serum IgA, serum amino acids, urine organic acids, serum acylcarnitine, creatine kinase, ESR, CRP, and thyroid studies. (The authors did not evaluate iron status.) 3rd tier: Then, if evidence of chronic liver disease, patients were offered a liver biopsy under general anesthesia.


  • 21% did not have significant liver disease (after 1st tier).  Also, 3 liver biopsies were normal.
  • 94% of 273 with evidence of chronic liver disease underwent liver biopsy; no significant complications were noted, though a small percentage had some discomfort.
  • Ultimately, 55% were determined to have NAFLD (75% of those who underwent liver biopsy.
  • The authors report that 61 patients who had a liver biopsy had another liver disease, including autoimmune hepatitis in 11, celiac disease in 4, sclerosing cholangitis in 1, and drug-induced in 6.
  • Advanced fibrosis was noted overall in 11% (38 of 347) and in 17% of those with NAFLD.  Those with advanced fibrosis were more likely to have higher aminotransferases (eg. ALT 120 U/L compared with 82 U/L), higher GGT, and higher ceruloplasmin; however, there was significant overlap.
  • Approximately half of NAFLD patients had steatohepatitis.

Take-home message: while this article does not resolve the issue of whether screening overweight/obese children is the best strategy, it does provide useful information in those with elevated liver tests.  Careful investigation for treatable causes (and possibly nontreatable) of liver disease is worthwhile in those with sustained abnormalities in transaminases.  At a minimum, tests for autoimmune hepatitis, celiac disease, viral hepatitis, and Wilson’s disease should be at the top of the list.

Related blog entries: