Usefulness of Transient Elastography for Non-Invasive Diagnosis of Liver Fibrosis in Pediatric Non-Alcoholic Steatohepatitis

Abstract

Background: Transient elastography (FibroScan®) is a non-invasive and rapid method for assessing liver fibrosis. While the feasibility and usefulness of FibroScan® have been proven in adults, few studies have focused on pediatric populations. We aimed to determine the feasibility and usefulness of FibroScan® in Korean children.

Methods: FibroScan® examinations were performed in 106 children (age, 5-15 years) who visited the Konyang University Hospital between June and September 2018. Liver steatosis was measured in terms of the controlled attenuation parameter (CAP), while hepatic fibrosis was evaluated in terms of the liver stiffness measurement (LSM). Children were stratified into obese and non-obese controls, according to body mass index (≥ or < 95th percentile, respectively).

Results: The obese group was characterized by significantly higher levels of aspartate aminotransferase (AST, 57.00 ± 48.47 vs. 26.40 ± 11.80 IU/L; P < 0.001) and alanine aminotransferase (ALT, 91.27 ± 97.67 vs. 16.28 ± 9.78 IU/L; P < 0.001), frequency of hypertension and abdominal obesity (abdominal circumference > 95% percentile) (P < 0.001), CAP (244.4-340.98 dB/m), and LSM (3.85-7.77 kPa) (P < 0.001). On FibroScan®, 30 of 59 obese children had fibrosis (LSM > 5.5 kPa), whereas the remaining 29 did not (LSM < 5.5 kPa). Obese children with fibrosis had higher levels of AST (73.57 ± 56.00 vs. 39.86 ± 31.93 IU/L; P = 0.009), ALT (132.47 ± 113.88 vs. 48.66 ± 51.29 IU/L; P = 0.001), and gamma-glutamyl transferase (106.67 ± 69.31 vs. 28.80 ± 24.26 IU/L; P = 0.042) compared to obese children without fibrosis. LSM had high and significant correlation (P < 0.05) with AST, ALT, homeostasis model assessment for insulin resistance, and AST-to-platelet ratio index.

Conclusion: FibroScan® is clinically feasible and facilitates non-invasive, rapid, reproducible, and reliable detection of hepatic steatosis and liver fibrosis in the Korean pediatric population.

Keywords: Child; Liver Fibrosis; Non-Invasive Diagnosis; Nonalcoholic Fatty Liver Disease.

Fig. 1. Flow chart of the study protocol and overview of the study population.

KYUH = Konyang University Hospital, BMI = body mass index, LSM = liver stiffness measure.

Fig. 2. Box-whisker plots of liver fibrosis and steatosis according to obesity status. (A) LSM values, which reflect fibrosis, and (B) CAP values, which reflect fat accumulation, were significantly higher in the obese group than in the control group.

Boxes denoted the interquartile range with the upper and lower horizontal edges representing the 75th and 25th percentiles, respectively. The central horizontal lines represented the medians. The vertical whisker above and below the boxes represented the range of outlying data points up to 1.5 times the interquartile range, and the star and circle represented the extreme and outlier, respectively. LSM = liver stiffness measure, CAP = controlled attenuation parameter.

Fig. 3. Correlation of liver fibrosis with steatosis. CAP values, which reflect fat accumulation, and LSM values, which reflect fibrosis, were significantly and positively correlated across the study population regardless of obesity status or sex.

CAP = controlled attenuation parameter, LSM = liver stiffness measure.

Fig. 4. Incidence of liver fibrosis in non-obese children (control group). (A) Logarithmically converted LSM values presented relatively normal distribution, with a value of 3.5 and 5.5 kPa corresponding to the 5th and 95th percentile thresholds, respectively. (B) The distribution of LSM values was independent of age (5–15 years).

LSM = liver stiffness measure.

Fig. 5. Correlation of liver fibrosis with liver function and NAFLD predictive indices in obese children.

AST = aspartate aminotransferase, LSM = liver stiffness measure, ALT = alanine aminotransferase, HOMA-IR = homeostasis model assessment for insulin resistance, APRI = AST-to-platelet ratio index, NAFLD = non-alcoholic fatty liver disease.