Nonalcoholic fatty liver disease, liver fibrosis, and cardiometabolic risk factors in adolescence: a cross-sectional study of 1874 general population adolescents

Abstract

Context: The impact of adolescent nonalcoholic fatty liver disease (NAFLD) on health, independent of fat mass, is unclear.

Objective: The objective of the study was to determine the independent (of total body fat) association of ultrasound scan (USS)-determined NAFLD with liver fibrosis, insulin resistance, and dyslipidemia among healthy adolescents.

Design: This was a cross-sectional analysis in participants from a UK birth cohort.

Participants: One thousand eight hundred seventy-four (1059 female) individuals of a mean age of 17.9 years participated in the study.

Main outcomes: USS assessed liver stiffness (shear velocity, an indicator of fibrosis) and volume, fasting glucose, insulin, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine amino transferase, aspartate amino transferase, γ-glutamyltransferase, and haptoglobin.

Results: The prevalence of NAFLD was 2.5% [95% confidence interval (CI) 1.8-3.3] and was the same in females and males. Dual-energy X-ray absorptiometry determined total body fat mass was strongly associated with USS NAFLD: odds ratio 3.15 (95% CI 2.44-4.07) per 1 SD (∼10 kg) fat mass. Those with NAFLD had larger liver volumes and greater shear velocity. They also had higher fasting glucose, insulin, triglycerides, low-density lipoprotein cholesterol, alanine amino transferase, aspartate amino transferase, γ-glutamyltransferase, and haptoglobin and lower high-density lipoprotein cholesterol. Most associations were independent of total body fat. For example, after adjustment for fat mass and other confounders, hepatic shear velocity [mean difference 22.8% (95% CI 15.6-30.5)], triglyceride levels [23.6% (95% CI 6.0-44.2)], and insulin [39.4% (95% CI 10.7-75.5)] were greater in those with NAFLD compared with those without NAFLD.

Conclusion: In healthy European adolescents, 2.5% have USS-defined NAFLD. Even after accounting for total body fat, those with NAFLD have more adverse levels of liver fibrosis and cardiometabolic risk factors.

Figure 1.

Participant flow from original birth cohort to the adolescent USS substudy used in this paper.

Figure 2.

Distribution of fat mass for those with and without USS liver fat.

Figure 3.

Multivariable associations of ultrasound scan liver fat with insulin resistance and liver fibrosis. The figure shows ORs (dots) and their CIs (vertical lines) for the association of USS fatty liver with liver fibrosis (the two results on the left) and insulin resistance (the two resuluts on the right), both without (model 1) and with (model 2) adjustment for fat mass. Model 1 was adjusted for age, sex, social class, and ethnicity. Model 2 was as model 1 but with additional adjustment for DXA fat mass, height, and height squared liver fibrosis defined as 1.39 m/s or greater shear velocity. Insulin resistance was defined as 90th percentile or greater of sex-specific fasting insulin (90th percentile: females, 86.44 pmol/L; males, 87.80 pmol/L).