Case-Based Review

Recognition and Management of Children with Nonalcoholic Fatty Liver Disease

Journal of Clinical Outcomes Management. 2016 March;23(3)

References

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What is the differential for children with suspected NAFLD?

The differential for NAFLD is remarkably broad and includes any condition that could lead to an elevated ALT or hepatic steatosis. Several of the more common etiologies in the differential are listed in the proceeding section. A list of “red flags” is shown in the Table and, if any are present, should alert the practitioner to the possible presence of alternative disease.

Autoimmune Hepatitis (AIH)

AIH is a progressive necro-inflammatory disorder of the liver characterized by elevated aminotransferases, positive autoantibodies, and distinctive histologic features. AIH is believed to occur in genetically predisposed patients in response to an environmental trigger. There is a female predominance and it can present in any age or ethnic group.

AIH is divided in 2 subtypes. Type 1 disease is characterized by a positive antinuclear (ANA) antibody and anti-smooth muscle antibody. More commonly, it presents in adolescence with an indolent course—many patients are asymptomatic until they develop features of cirrhosis and portal hypertension. Conversely, type 2 AIH is characterized by a positive liver kidney microsomal (LKM) antibody and tends to present acutely in young children. It is important to note that antibody titers can be falsely positive in a significant percentage of patients and, in such cases, are often mildly elevated [38]. We strongly suggest children with positive autoantibody titers be evaluated by a specialist.

Treatment should be started promptly to avoid progression to cirrhosis and should also done so in consultation with a pediatric gastroenterologist or hepatologist. The prognosis of AIH with immunosuppression is favorable, with long-term remission rates of approximately 80%. Transplantation is typically required in the remaining 10% to 20% [39].

Celiac Disease

Celiac disease is an autoimmune, inflammatory enteropathy caused by exposure to gluten in genetically susceptible individuals. Up to a third of all children presenting with celiac will have an elevated serum ALT [40]. Additional symptoms/features are both variable and nonspecific: abdominal pain, poor growth, diarrhea, or constipation, among others. Celiac is diagnosed by duodenal biopsy or a sufficiently elevated tissue transglutaminase antibody level [41]. Treatment with a strict gluten-free diet will resolve the enteropathy and normalize the serum aminotransferases.

Wilson’s Disease

Wilson’s disease is a metabolic disorder leading to copper deposition in the liver, brain, cornea, and kidneys. It is caused by an ATP7B gene mutation and inherited in an autosomal recessive fashion. Patients may present with asymptomatic liver disease, chronic hepatitis, acute liver failure, or with symptoms of portal hypertension. Neuropsychiatric symptoms may also be prominent. Screening tests include a serum ceruloplasmin and 24-hour urinary copper quantification. Because diagnosing Wilson’s disease can be challenging, however, further testing should occur in consultation with a pediatric gastroenterologist or hepatologist.

Viral Hepatitis

Chronic viral infections such as hepatitis B and C are still common etiologies of liver disease in the United States. However, universal vaccination and blood donor screening have reduced the risk of transmission; new antiviral agents will likely further decrease the prevalence and transmission risk over time. Acute viral hepatitis—cytomegalovirus, Epstein-Barr virus, hepatitis A, or hepatitis E—should also be considered in children who present with appropriate symptoms and an elevated ALT.