Nonalcoholic Fatty Liver Disease in Lean Adolescents

With the rising epidemic of obesity, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in children and adolescents in the United States. NAFLD is defined as hepatic steatosis in the absence of other alternate causes such as significant alcohol intake, viral hepatitis or medications. Contrary to the belief that NAFLD is almost always associated with obesity, it has been recently recognized that fatty liver disease can occur in people with no significant obesity, termed as “lean NAFLD” or “nonobese NAFLD.”

The prevalence of lean NAFLD in adults varies widely, ranging from 3 to 30 percent depending on the study population, diagnostic modality and body mass index (BMI) cutoffs used to define lean subjects.1 Most of the evidence on lean NAFLD is based on Asian population or community-based adult studies. Evidence is lacking on lean NAFLD in the pediatric population. Therefore, we aimed to estimate the population-based prevalence of NAFLD among lean U.S. adolescents (12-18 years) and to assess the characteristics and risk factors of NAFLD in this unique population.2

Study design

Our team performed a retrospective data analysis of adolescents aged 12-18 years with BMI < 85th percentile who were enrolled in the National Health and Nutrition Examination Survey (NHANES) database during the 2005-2014 cycles. NHANES is a cross-sectional survey of U.S. civilian, noninstitutionalized population conducted by the National Center for Health Statistics (NCHS) to assess the health and nutrition status of adults and children. This program conducts an annual survey of a nationally representative sample of about 5,000 persons from different counties in the U.S.

A BMI cutoff of less than the 85th percentile for specific age and gender was used to define lean adolescents. Suspected NAFLD was defined as alanine aminotransferase (ALT) > 25.8 U/L for boys and > 22.1 U/L for girls, as proposed by the SAFETY study.3 Components of metabolic syndrome such as hypertriglyceridemia, low high density-lipoprotein cholesterol (HDL-C), hypertension, prediabetes/diabetes and insulin resistance were also assessed. We excluded subjects with viral hepatitis (B or C), use of hepatotoxic medications and those missing ALT to define NAFLD.

Lean NAFLD does exist in American adolescents

The study analyzed 1,482 lean adolescents, corresponding to the weighted U.S. population of over 18 million. The estimated prevalence of suspected NAFLD in lean adolescents for each of five cycles during 2005-2014 were 6.9 percent, 8.8 percent, 8.1 percent, 5 percent and 11.5 percent, respectively. Therefore, the mean estimated prevalence of suspected NAFLD among the lean U.S. adolescents during 2005-2014 was 8 percent. Fortunately, we didn’t find any trend in lean NAFLD in contrast to NAFLD in obese patients, which studies have shown has increased significantly in the past two decades.

Characteristics of lean NAFLD in American adolescents

For a better understanding, we compared the lean American adolescents with and without NAFLD. Interestingly, metabolic syndrome components such as low HDL-C (15.5 percent vs. 6.8 percent; P value 0.016), hypertriglyceridemia (10 percent vs. 3.9 percent; P value 0.028) and insulin resistance (29.9 percent vs. 20.4 percent; P value 0.053) are more frequent among lean adolescents with suspected NAFLD compared with lean healthy adolescents. In addition, non-Hispanic black lean adolescents had lower rates of suspected NAFLD than their Caucasian counterparts. More important, lean adolescents with suspected NAFLD had approximately four times higher odds of having insulin resistance compared to lean healthy controls.

Importance of recognizing lean NAFLD in adolescents

Lean NAFLD is an evolving concept with much of the information yet to be understood, such as clinical and prognostic implications, especially in children. Regardless, lean NAFLD most likely represents a distinctive phenotypic spectrum of NAFLD. The complex interplay of visceral instead of general obesity, high fructose or cholesterol consumption, gut microbiota and genetic predisposition might play a role in the development of NAFLD in lean subjects, but the contribution of each factor might be different from that of in obese NAFLD.

In the absence of traditional obesity, hepatic steatosis in these lean subjects could be under-recognized. Hence, it is important to be aware of this unique phenotype of NAFLD and to identify lean patients at risk for NAFLD, as they might have the same or even worse outcomes compared with obese patients with NAFLD.

References

1. Kim, D, Kim WR. Nonobese Fatty Liver Disease. Clin Gastroenerol Hepatol. 2017;15(4):474-485.
2. Conjeevaram Selvakumar PK, Kabbany MN, Lopez R, Rayas MS, Lynch JL, Alkhouri N. Prevalence of Suspected Nonalcoholic Fatty Liver Disease in Adolescents in the United States. J Pediatr Gastroenterol Nutr. 2018;67(1):75-79.
3. Schwimmer JB, Dunn W, Norman GJ, et al. SAFETY study: alanine adminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease. Gastroenterology. 2010;138(4):1357-64, 1364.e1-2.

Dr. Selvakumar is a pediatric gastroenterologist at Cleveland Clinic Children’s whose primary area of interest is liver diseases in children.