Summary

In the United States and around the world, childhood obesity has become a major health problem. Along with the rise in obesity, is an increase in the co-morbidities of obesity, including non-alcoholic fatty liver disease (NAFLD). NAFLD is a chronic liver disease characterized by abnormal lipid deposition in hepatocytes that occurs in the absence of excess alcohol intake. NAFLD comprises a spectrum of diseases, ranging from simple steatosis to steatosis in association with necro-inflammatory disease (non-alcoholic steatohepatitis or NASH). An estimated 30 million adults and 1.6 million children in the US have NAFLD and up to 30% are estimated to have NASH. NASH can be a more aggressive disease that leads to liver fibrosis and cirrhosis in about 20% of cases. Only the rare case advances to cirrhosis in childhood because of its slow progression. However, NAFLD is rapidly increasing the need for liver transplant in young adults. Because of its high prevalence, it has become one of the most common reasons children are referred to pediatric hepatologists.[1] In this article, we will review risk factors, warning signs, and screening for NAFLD in children, as well as diagnosis, treatment and prevention strategies.

Educational objectives

At the conclusion of this activity, participants will be able to:

• Identify risk factors and warning signs of nonalcoholic fatty liver disease (NAFLD) in children
• Screen overweight children for NAFLD
• Discuss diagnosis, treatment and prevention of NAFLD

CME credit

This is an article from The Child's Doctor, Fall 2006 issue. You may take the quiz for learning purposes, but credits are no longer valid.

Author disclosures

Dr. Louthan has no industry relationship to disclose and does not refer to products that are still investigational or not labeled for the use in discussion.

Dr. Sundaram has no industry relationship to disclose and does not refer to products that are still investigational or not labeled for the use in discussion.

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NAFLD risk factors

NAFLD was originally identified in the 1980s and named non-alcoholic fatty liver disease to distinguish it from alcoholic fatty liver disease, which it resembles histologically.[2] This disease occurs primarily in overweight individuals, though affected lean patients have also been seen. Studies have shown that 10% to 30% of overweight children have NAFLD.

The prevalence of the disease varies significantly by race. Mexican American overweight children have the highest risk, with some studies showing that over 30% will be affected.[3] Overweight African American children have a much lower incidence, closer to 6%,[4] despite their high risk of type 2 diabetes.

Boys seem to have a slightly greater risk than girls, approximately 2:1. Most children diagnosed with NAFLD are teenagers, though diagnosis in pre-pubertal children is becoming increasingly common. A majority of children who have NAFLD are also insulin resistant, and a few are overtly diabetic. NAFLD is now considered the hepatic component of the metabolic syndrome. Children may have a family history of type 2 diabetes and/or an overweight relative who also had fatty liver disease.

Warning signs

Unfortunately, NAFLD is typically asymptomatic until the late stages. A high level of suspicion is required in order to identify this disease. The most common presentation is elevation of serum transaminases on blood work done for unrelated reasons. Another chance identification occurs when a child undergoes evaluation for abdominal pain and either an ultrasound or a computed tomography (CT) scan demonstrates increased echogenicity in the liver, consistent with fatty liver. Children with symptoms may complain of right upper quadrant, periumbilical or non-specific abdominal pain.

Screening

Screening children for NAFLD remains somewhat controversial. This controversy exists as the treatment of NAFLD is not specific and is similar to that for obesity. We believe, however, that screening and diagnosis of NAFLD in high risk populations may be important, as families can respond to weight loss counseling with more commitment when confronted with a liver disease diagnosis. Screening for NAFLD should be considered in all overweight children over the age of 8 years. Screening children at high risk for NAFLD, such as those with a family history of type 2 diabetes mellitus or NAFLD, or with co-morbidities such as hypertension, diabetes or hyperlipidemia may be of higher yield. Mexican American overweight children should be considered the highest risk group and are routinely screened in our practice.

The simplest method of screening is by serum transaminases. An alanine transaminase (ALT) over 40 for both boys and girls is abnormal and should initiate further testing. In NAFLD, the ALT usually ranges from 2 to 5 times normal and often is higher than the aspartate transaminase (AST).

Imaging for fat in the liver is not sensitive or specific, but can be helpful if positive. The liver must be at least 33% fat before ultrasound or CT can reliably detect the fat. Magnetic resonance imaging (MRI) is more sensitive and can provide actual estimates of fat percentage. This imaging modality, however, is currently utilized primarily in the context of clinical research.

Diagnosis

Most children who are found to have a chronically elevated serum ALT need to be referred to a pediatric gastroenterologist/hepatologist for further evaluation. The majority of overweight children with ALT elevation will eventually be diagnosed with NAFLD, however an increase in ALT in an obese child is not specific for NAFLD. Diseases such as Wilson disease, autoimmune hepatitis, hepatitis B and C, and alpha-1 anti-trypsin deficiency can present in a similar fashion. The presence of these diseases must be ruled out by blood tests before a clinical diagnosis of NAFLD can be made.

Occasionally a liver biopsy is necessary to further clarify the diagnosis. Liver biopsy is the gold standard for diagnosis and it is the only test that can reliably differentiate between the more benign simple steatosis and NASH. The severity of NAFLD on biopsy does not correlate with the degree of elevation of ALT. ALT tends to fluctuate over time and may even normalize at times, despite the continued presence of disease. In our experience, some children with very mild elevations of ALT have had advanced fibrosis from NASH on liver biopsy.

Treatment

The only proven therapy for NAFLD in children is weight loss.[5] A small but significant improvement in the BMI (body mass index) of a child can improve serum transaminases, and may also improve liver histology. Studies of adults who have undergone gastric bypass and lost large amounts of weight show that even the fibrosis of NASH can be reversible.

The keys to improvement of BMI are lifestyle changes that modify calorie intake and decrease sedentary time. Families can easily reduce children's consumption of high calorie drinks, such as sodas, juices, and sports drinks. Decreasing sedentary time increases the activity level of the child and has been shown to be more effective for weight loss than prescribed exercise. Limiting TV or video games to ½ hour per day is an achievable goal for most children and families. Routine increase in aerobic exercise is also effective, although families find complying with these regimens more difficult.

For children with more advanced disease, an FDA-approved medication currently does not exist. Research on antioxidant therapies, antifibrotic medications, and medications addressing insulin resistance is underway.

Prevention

Prevention of NAFLD is critical. Promoting physical activity and healthy eating early in the lives of children may decrease the epidemic of obesity and with it NAFLD. During well child visits in the early pre-school years, parents should be educated not to purchase televisions for their children's bedrooms and not to buy sweetened beverages. Parents should be encouraged to incorporate healthy food choices and active play into the lifestyles of their entire families.

Research

Research is ongoing at Children's Memorial Hospital on many aspects of NAFLD, including pathophysiology and potential treatments. Additionally, multi-center pediatric trials are ongoing at the hospital, as part of the National Institutes of Health Non-Alcoholic Steatohepatitis Clinical Research Network.

Conclusion

NAFLD is a common pediatric liver disease that will lead to increasing morbidity and mortality as the obesity epidemic continues. Every effort should be made to identify and diagnose children at risk. While lifestyle changes remain the most important treatment at this time, severely affected children are candidates for ongoing treatment studies.

R E F E R E N C E S

[1.] Mager D, Roberts E. Nonalcoholic fatty liver disease in children. Clinics in Liver Disease 2006;10:109-131.

[2.] Ludwig J, et al. Nonalcoholic Steatohepatitis: Mayo Clinic experiences a hitherto unamed disease. Mayo Clinic Procedings 1980;55(7):434-438.

[3.] Schwimmer JA, et al. Influence of gender, race and ethnicity on suspected fatty liver in obese adolescents. Pediatrics 2005;115:e561-565.

[4.] Louthan MV, et al. Decreased prevalence of nonalcoholic fatty liver disease in black obese children. Journal of Pediatric Gastroenterology and Nutrition 2005;41:426-429.

[5.] Huang M, et al. One-year intense nutritional counseling results in histologic improvement in patients with non-alcoholic steatohepatitis: A pilot study. American Journal of Gastroenterology, 2005;100:1072-1078.