Abstract and Introduction
Abstract
Background Screening overweight and obese children for non-alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation.
Aim To determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD.
Methods Information generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed.
Results Non-alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P < 0.05) higher screening ALT (98 ± 95) than children with liver disease other than NAFLD (86 ± 74). Advanced fibrosis was present in 11% of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN had a sensitivity of 57% and a specificity of 71%.
Conclusions Screening of overweight and obese children in primary care for NAFLD with referral to paediatric gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner.
Introduction
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. The diagnosis of NAFLD requires that 5% or more hepatocytes have macrovesicular steatosis, and that other liver diseases and/or clinical conditions, which may cause steatosis, are excluded. Approximately 25% of children with NAFLD have a progressive sub-phenotype known as non-alcoholic steatohepatitis (NASH). Some children with NASH will develop cirrhosis and end-stage liver disease. Thus, NAFLD is not a singular diagnosis, but a clinical–pathological diagnosis that encompasses a broad spectrum of liver disease ranging from isolated steatosis to steatohepatitis, fibrosis and cirrhosis.
For the years 1993–2003, the prevalence of NAFLD in children aged 2–19 years was estimated to be 9.6%. Studies have consistently shown that obesity is one of the most important risk factors for paediatric NAFLD. An overweight or obese child with elevated alanine aminotransferase (ALT) is typically considered to have suspected NAFLD. A recent report from the National Health and Nutrition Examination Survey demonstrated that the prevalence of suspected NAFLD in children age 12–19 in the United States more than doubled from 1988–1994 to 2007–2010.
In 2005, a report from UC San Francisco and Stanford University noted that general paediatricians were 'underscreening' overweight children for NAFLD. Beginning in 2007, major medical societies published guideline statements regarding screening overweight and obese children for NAFLD. The positions of these societies are summarised in Table 1. Recommendations for screening have been made by paediatricians, endocrinologists and paediatric gastroenterologists. The paediatric guidelines state that overweight or obese children ≥10 years should be screened for NAFLD using serum ALT and aspartate aminotransferase (AST). There is, however, some controversy surrounding screening children for NAFLD. Using published literature through June 2011, the American Gastroenterology Association, American Association for the Study of Liver Diseases and the American College of Gastroenterology developed a Practice Guideline on the diagnosis and management of NAFLD, which was jointly published in Gastroenterology,Hepatology and American Journal of Gastroenterology in June 2012. The Practice Guideline states, 'Due to a paucity of evidence, a formal recommendation cannot be made with regards to screening for NAFLD in overweight and obese children despite a recent expert committee recommendation for biannual screening for liver disease with liver enzyme measurements in this population'.
In the absence of uniform guidance, physicians must make their own decision whether or not to screen overweight children for NAFLD. Many primary care providers are screening overweight and obese children for NAFLD and many of these children identified as having suspected NAFLD are referred to paediatric gastroenterology for evaluation. The diagnostic outcomes for such children with suspected NAFLD who were referred to paediatric gastroenterology have not been reported. Therefore, we sought to address critical gaps in the knowledge base with the following study aims:
(i) To describe the population of children who were identified with suspected NAFLD through screening in primary care and referred to paediatric gastroenterology.
(ii) To determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD.
(iii) To determine the frequency of NASH amongst overweight and obese children who were identified with suspected NAFLD through screening in primary care and referred to paediatric gastroenterology.
(iv) To determine the frequency of advanced fibrosis amongst overweight and obese children who were identified with suspected NAFLD through screening in primary care and referred to paediatric gastroenterology.
(v) To determine the diagnostic performance of ALT two times the upper limit of normal (ULN) for the above outcomes amongst overweight and obese children who were identified with suspected NAFLD through screening in primary care and referred to paediatric gastroenterology.