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Prevalence of fatty liver in children and adolescents.

Article Excerpt
THE GROWING EPIDEMIC of childhood obesity has prompted studies of the prevalence of obesity-related conditions, such as hypertension, hypercholesterolemia, and the metabolic syndrome. (1-4) Reports of pediatric fatty liver disease and steatohepatitis in obese children have been increasing (5-7) and include cases of cirrhosis (8-11) and liver transplantation. (12) However, despite the potentially serious nature of fatty liver in children, the prevalence is unknown.

Efforts to determine the prevalence of fatty liver in children have been limited to indirect measures, such as blood tests or ultrasound, to predict a histologic outcome. In 1989, based on ultrasound, fatty liver prevalence was estimated to be 2.6% in school-aged children in northern Japan. (13) Projections for children in the United States are considerably higher, (14) although no population-based estimates are available. All of the other studies have been limited to children selected for the conditions of obesity. Taken together, the prevalence of fatty liver in obese children in China, Italy, Japan, and the United States has been reported to be between 10% and 77%. (15-18) The wide range in estimates of prevalence is attributable in part to the difficulty in determining the presence or absence of fatty liver using noninvasive tests. Therefore, we conducted the Study of Child and Adolescent Liver Epidemiology (SCALE) to determine the prevalence of fatty liver as diagnosed by histology in a population-based sample of children and adolescents.

METHODS

SCALE Study Design

Given that fatty liver is a histologic diagnosis, numerous problems exist in trying to estimate prevalence. Children without fatty liver are unlikely to undergo liver biopsy. However, noninvasive surrogate markers lack sufficient sensitivity and specificity. Thus an autopsy-based study design is the only means of assessing population-based histology. The county of San Diego is particularly well suited to such a study based-on its size as the fourth largest county in the United States and its substantial racial and ethnic diversity. The county of San Diego medical examiner investigates the cause of death in all homicides, suicides, and accidental deaths. The medical examiner also investigates natural deaths when the cause of death is unknown. However, the medical examiner does not perform a postmortem examination for those children who have been seen by a physician within 20 days before death and have a known cause of death.

We included all children age 2 through 19 years at the time of death who had an autopsy performed by the medical examiner from 1993 to 2003. We set a minimum age of 2 years, because this is the youngest age reported for biopsy-proven steatohepatitis. (10) The upper age limit was set at 19 years to mirror the age brackets used by the US Census Bureau. Exclusion criteria were insufficient data (missing clinical data or the absence of a liver slide for review) or identification of a factor that may unduly influence liver histology (inpatient clinical care or alcohol or drug use). SCALE was conducted with approval from the county of San Diego and the University of California, San Diego.

Clinical Data Collection

Medical examiner records were reviewed for age, gender, race, ethnicity, weight, height, toxicology, and the mode and cause of death. BMI was calculated as the weight (kilograms) divided by the height (meters) squared. Weight status was defined according to the Institute of Medicine as underweight (BMI [less than or equal to] 5th percentile), normal weight (BMI > 5th and < 85th percentile), overweight (BMI [less than or equal to] 85th and < 95th percentile), and obese (BMI [less than or equal to] 95th percentile). (19) BMI varies with age and gender; therefore, to compare subjects independently of age and gender, BMI Z-scores were calculated. The BMI z score represents the number of SDs from the national reference mean that a subject is for a given age and gender.

Assessment of Liver Histology

A hepatopathologist (C.B.) with expertise in pediatric fatty liver reviewed a section of liver tissue stained with hematoxylin and eosin for all of the...

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