Should We Screen Children for Fatty Liver Disease?

[Guest guest]

Question

With the increasing rates of obesity in children, what are the current

recommendations for screening for, and management of, fatty liver disease?

*Response from 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.

www.medscape.com

--

Ortiz, MS, RD

*The FRUGAL Dietitian* <http://www.thefrugaldietitian.com>

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