Waist-to-height ratio is a useful index for nonalcoholic fatty liver disease in children and adolescents: a secondary data analysis

This study used a correlational cross-sectional design in which anthropometric measure and NAFLD were assessed concurrently in prepubertal children and adolescents. Ethical approval was provided by the institutional review board ethical committee (Chang-Gung Memorial Hospital Ethics Committee No 102-4399B).

From December 2012 to September 2013 in Yunlin County, Taiwan, 12,348 residents underwent a community-based annual health checkup. We selected 10- to 19-year-olds for the study and obtained the informed consent from all of them. The exclusion criteria were: (1) < 10 or >19 years old; (2) incomplete health survey, anthropometric measurements, or laboratory data; (3) hepatitis B (HBV), hepatitis C (HCV), or both; (4) prior hepatic surgery; (5) habitual alcohol drinking; (6) liver cirrhosis, nodules, or tumors revealed by ultrasound scan. We finally enrolled 1210 participants (Fig. 1).

A noninvasive oscillometric monitor (Omega 1400; Invivo Research Inc., Orlando, FL, USA) was calibrated and then was used to measure blood pressure (BP) with a standard procedure and appropriate cuff size. Every participant’s BP was measured twice and recorded. If the difference between first and second BP value was >10 mmHg, BP was measured a third time. The mean BP value was calculated in twice closest BP value and hypertension was defined as an average systolic or diastolic blood pressure level that was in the 95th percentile or greater based on at least three separate readings under guideline of the National High Blood Pressure Education Program (NHBPEP) [14].

Height (Ht), weight (Wt), and body mass index (BMI) were anthropometric measurements and plotted on Taiwan growth curves [15]. Height and body weight was measured under light clothes and bare feet. Body Mass Index (BMI) was calculated for each participantby using the standard formula (weight in kilograms divided by square of the height in meters). Based on the nationwide standard set by the Taiwan Bureau of Health Promotion (BHP, 2013), BMI was plotted on the age and sex-specific cutoff points to define the body size of children.

An anthropometric tape was used to measure waist circumference (WC) and hip circumference. WC was measured at the level midway between the lowest rib margin and the iliac crest. Hip circumference was measured at the maximum protuberance of the buttocks in a standing position.

Venous blood samples were drawn from all participants after a 12-h overnight fast and delivered to the laboratory on the same day. The serum collected in the morning was measured (7600 Chemistry Analyzer; Hitachi Medical Corp., Tokyo, Japan) to detect serum uric acid, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl-transferase (GGT)), and creatinine (Cr). Seropositivity of antibodies to HCV was assessed by means of an electrochemiluminescence immunoassay and seropositivity to HBV was assessed with a semiquantitative determination of hepatitis B surface antigens by using a sandwich radioimmunoassay (Elecsys E-170; Cobas Analyzer; Roche Diagnostics, Indianapolis, IN).

Alcohol drinking, betel nut chewing, and cigarette smoking habits were evaluated. Participants were classified as non-user (never drank alcohol/chewed betel-nut/smoked cigarettes, or had not drunk/chewed/smoked for the previous year), or current user (currently drinking/chewing/smoking).

Right upper quadrant ultrasound was performed on one of three units: an Aloka SSD 4000 (Hitachi Aloka Medical Ltd., Tokyo, Japan) with a UST-979-3.5 curved array transducer; CGM OPUS 5000 (Chang Gung Medical Technology Co., Ltd., Taipei, Taiwan) with a CLA35 curved array transducer; or an Acuson S2000 Ultrasound System (Siemens, Malvern, PA, USA) by using a C4-1 MHz curved array transducer. Technical parameters were adjusted for each patient with the standard protocol for a right upper quadrant ultrasound examination. The liver was considered normal if the echo-texture was homogeneous without acoustic attenuation, the portal veins were visible, the diaphragm was well visualized, and echogenicity was similar or slightly higher than that of the renal parenchyma. The diagnosis of fatty liver was based on the differences between the echogenicity in the liver and the kidney, vascular blurring of the hepatic vein trunk, and deep attenuation in the right hepatic lobe. The severity of fatty liver change was classified according to the standardized ultrasonographic criteria: grade 0, normal liver, a normal echo texture and absence of fatty change; grade 1, mild fatty liver change, a mildly increased echogenicity in the parenchyma comparing with the kidney, and slightly impaired visualization of intrahepatic vessels and diaphragm; grade 2, medium grade diffuse increased in hepatic echogenicity, mild deterioration in the image of the diaphragm and intrahepatic vessels; grade 3, moderate-to-severe fatty liver change, marked increase in fine echoes in the parenchyma with poor or non-visualization of the intrahepatic vessel borders, diaphragm, and posterior right lobe of the liver. The criteria for severe fatty liver changes were obvious and unambiguous. All images were reviewed on a picture archiving and communication system (Centricity PACS; GE Healthcare, Allendale, NJ, USA).

(1) NAFLD was defined as (a) ultrasonographic evidence of hepatic steatosis, and (b) absent current alcohol consumption, hereditary disorders, or using steatogenic medication.

(2) Obesity was defined when BMI was ≥ the 95th percentile [15].

(3) Components of International Diabetes Foundation defined MetS [16]: The criterion of waist circumference for MetS was infeasible because of absent update references in Taiwan. For children 10-16 years old, MetS components included triglyceride ≥150 (mg/dL), HDL < 40 (mg/dL), SBP ≥ 130 mmHg or DBP ≥ 85 mmHg and fasting glucose ≥100 mg/dL. For children >16 years old, MetS criteria were triglyceride ≥150 (mg/dL), HDL < 40 mg/dL in males and <50 mg/dL in females, SBP ≥ 130 mmHg or DBP ≥ 85 mmHg and fasting glucose ≥100 mg/dL.

SPSS 19.0 (SPSS, Inc., Chicago, IL, USA) was used for all analyses. Numeric variables were expressed as mean ± standard deviation (SD) and categorical variables as number (percent). Continuous data for the study group and comparison group were compared using Student’s t test. Categorical data were analyzed using χ² or Fisher’s Exact tests, and 95% CIs and multivariate logistic regression analyses were used to identify the best subset of independent predictors. All tests were two-sided and significance was set at P < 0.05. A multiple logistic regression analysis was used to identify the variables affecting the dependent variable NAFLD (using odds ratios [ORs] and 95% CIs). The independent variables included in the analyses were age groups, sex, and BMI categories.

The cutoff value for the risk score was determined by using the receiver operating characteristic (ROC) curve procedure. The ROC curve was plotted for NAFLD; sensitivity was plotted on the y-axis and the false-positive rate (1−specificity) was plotted on the x-axis.

The data of 616 (50.1%) females and 594 (49.1%) males (mean (SD) age: 15.5 (2.8) years) were analyzed (Table 1). The overall prevalence of obesity in the study population was 16.3%. Those obese subjects were predominant in male gender (male vs female 62.4% vs. 37.6%; P < 0.001) with similar portion of smoking and betel nut chewing compared with non-obese group. Higher BMI (28.3 ± 3.2 vs. 19.9 ± 2.7; P < 0.001), body weight (74.7 ± 15.5 vs. 51.7 ± 11.6; P < 0.001), and waist circumference (73.5 ± 12.6 vs. 71.52 ± 10.44; P = 0.020) were observed in obese group; however, the BP or laboratory data were insignificantly different.

The participants were divided into two groups based on whether they had been ultrasonically proved fatty liver, and, according to ultrasonographic criteria, 167 (13.8%) of the participants were diagnosed with NAFLD (Table 2). The percentage differences between NAFLD participants was not significant based on sex (male: 54.5% vs. female: 48.2%; OR: 1.285; 95% CI: 0.926-1.784), age (18.0 ± 1.9 vs. 15.1 ± 2.8; OR: 1.823; 95% CI: 1.627-2.042), or obesity (21.0% vs. 15.5%; OR: 1.442; 95% CI: 0.958-2.170) in comparison with the non-NAFLD group. Additionally, NAFLD group members had a significantly greater WHR (0.86 ± 0.08 vs. 0.79 ± 0.07; OR: 2.556; 95% CI: 2.106-3.104), greater WHtR (0.51 ± 0.07 vs. 0.44 ± 0.05; OR: 3.885; 95% CI: 2.331-5.233) as well as higher BMI than those in the non-NAFLD group. Although serum Cr and fasting blood glucose levels were non-significant between groups, NAFLD group members had significantly higher BPs and lipid profiles (LDL, VLDL, TG, and TC levels); ALT, AST, uric acid, and GGT levels; and lower HDL levels than non-NAFLD group members. Participants with higher grade NAFLD also had a significantly larger WHtR. (Figure 2) In addition, participants with more than two IDF-defined MetS components had a significantly larger WHtR than subjects with less than two points (0.49 vs 0.44; P < 0.001) (Fig. 3).

Hierarchical multiple logistic regression showed that the WHtR was most significantly associated with NAFLD (adjusted OR: 2.600; 95% CI: 1.909-3.549; P < 0.001) after final adjustments (Table 3).

The WHtR AUC (0.80; CI: 0.760-0.839) predicting NAFLD was significantly higher than the WHR AUC (0.755; CI: 0.714-0.795) (Fig. 4). The cutoff value of the WHtR for children and adolescents was 0.469, which indicates a high risk of having NAFLD if it was above the value (sensitivity: 70.1%; specificity 76.9%).

A liver biopsy has been a gold standard in the clinical diagnosis of NAFLD, but it is not well suited for screening or monitoring children because it is invasive and expensive, and it can cause complications in a pediatric physical examination. Ultrasonic sensitivity is acceptable, and interoperative differences can be reduced by experienced ultrasound users or by a review. A small regional study will limit the accuracy of the findings, but a large nationwide study will increase it. Nambiar and colleagues [30] had reported that error associated with the WHtR was “clinically and biologically acceptable”.