Should We Screen Children for Fatty Liver Disease?

William F. Balistreri, MD


August 08, 2011


With the increasing rates of obesity in children, what are the current recommendations for screening for, and management of, fatty liver disease?

Response from William F. Balistreri, MD
Professor of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio; Staff Physician, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

The latest data suggest that 16% of children in the United States are obese and 32% are overweight.[1] Therefore, concern about the prevalence of nonalcoholic fatty liver disease (NAFLD) or the progressive form of fatty liver disease -- nonalcoholic steatohepatitis (NASH) -- is appropriate. Recent studies have indicated a progressive rise in the prevalence of NAFLD to its present status as the most common cause of chronic liver disease in adults in the United States.[2] A similar trend is anticipated for the pediatric population. At present, the prevalences of NAFLD and NASH in children are unknown because affected children are most often asymptomatic, perhaps manifesting only mild fatigue and obstructive sleep apnea. One clue to recognition is the close association between metabolic syndrome (hypertension, hypertriglyceridemia, and central adiposity) and NAFLD in children.[3] As in adults, waist circumference is a significant correlate of insulin resistance and fatty liver in children.[4]

The pathogenesis of NAFLD is the subject of multiple ongoing studies. One element that has become abundantly clear is the strong influence of genetic susceptibility. Schwimmer and colleagues documented fatty liver in 59% of the siblings of children with NAFLD and in 78% of their parents; this was a significantly higher incidence than that seen in siblings (17%) and parents (37%) of children without NAFLD.[5]Furthermore, recent studies suggest that specific genetic variation in PNPLA3 (a variant that confers genetic susceptibility to liver damage) is associated with increased levels of liver enzymes in children.[6,7] This predisposition to NAFLD is strongly influenced by the environment, including a high intake of added sugar and consumption of fructose-sweetened beverages.[8]

Unfortunately, no guidelines on screening strategies for fatty liver have been established. Obviously, the first step is recognition that a child is overweight or obese. Although clear definitions for body mass index exist, a large percentage of overweight and obese children and adolescents remain undiagnosed.[9]

The next step -- case finding for fatty liver disease -- is equally challenging because the ideal test is lacking.[10] NAFLD is not consistently or easily recognized. Traditionally, the diagnosis has relied on the detection of markers of liver injury such as aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels, fatty infiltration (on ultrasound or MRI), or assessment of fibrosis through the use of stiffness measurements.[11] However, these currently used methods cannot distinguish NASH from NAFLD, thus liver biopsy remains the gold standard for staging and grading. Multiple novel noninvasive methods for diagnosis and monitoring of NASH and NAFLD have been proposed, such as clinical scoring systems based on markers of fibrosis or fibrinogenesis.[12]These methods may help sort out which patients are candidates for liver biopsy.

The question that ultimately arises is: why should we be concerned about this disorder? We have recognized rapid progression of fibrosis in children with NASH/NAFLD over a short period of time.[13] Therefore, early detection with an attempt at intervention is clearly warranted. This may be the only way to forestall the projected epidemic of NASH cirrhosis in young adults in the next decade.

With respect to management, the Institute of Medicine has recently released early childhood obesity prevention policies that outline specific goals, recommendations, and potential actions.[14]The major objective is prevention through lifestyle modifications, such as promoting exercise and ensuring adequate nutrition for children, including the avoidance of added sugars. This is coupled with the minimization of "screen time" (TV and computers). Lifestyle modification is clearly warranted for all children with NAFLD because these measures have proven to be effective if adherence can be achieved, as shown in a recent study.[15] In this prospective cohort study, liver enzymes and steatosis decreased during a rigorous program of weight reduction through dietary and exercise recommendations.[15] In desperate situations, with significant comorbidities, bariatric surgery has been shown to lead to regression of advanced fibrosis.[16]

The quest for the "magic pill" to treat NAFLD has been less fruitful, with most proposed treatment strategies shown to be ineffective when subjected to placebo-controlled trials. A recent study of adults with NASH showed that vitamin E therapy (compared with placebo) was associated with a reduction in serum AST and ALT levels and a documented reduction in steatosis (P = .005) and lobular inflammation (P = .02) but no improvement in fibrosis scores (P = .24).[17]

In a similar fashion, the results of a study of the effect of vitamin E or metformin for treatment of NASH/NAFLD in children and adolescents (the Treatment of Nonalcoholic Fatty Liver Disease in Children [TONIC] trial) were recently published.[18] Neither vitamin E nor metformin was superior to placebo in achieving the primary outcome of a sustained reduction in ALT levels after 2 years. However, children with biopsy-proven NASH treated with vitamin E had significant improvement in secondary histologic outcomes, specifically an improvement over placebo in the degree of hepatocellular ballooning degeneration. This suggests that perhaps long-term administration of this antioxidant may lead to resolution of NASH.

The bottom line is that, just like in adults, NAFLD may now be the most common form of chronic liver disease in children. The incidence is likely to increase given the unabated epidemic of pediatric obesity. Treatment options are limited and pediatric screening and management guidelines are lacking. As in many pediatric diseases, the most effective strategy is prevention.


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