US Time-Harmonic Elastography: Detection of Liver Fibrosis in Adolescents with Extreme Obesity with Nonalcoholic Fatty Liver Disease

Abstract

Purpose To measure in vivo liver stiffness by using US time-harmonic elastography in a cohort of pediatric patients who were overweight to extremely obese with nonalcoholic fatty liver disease (NAFLD) and to evaluate the diagnostic value of time-harmonic elastography for differentiating stages of fibrosis associated with progressive disease. Materials and Methods In this prospective study, 67 consecutive adolescents (age range, 10-17 years; mean body mass index, 34.7 kg/m; range, 21.4-50.4 kg/m) with biopsy-proven NAFLD were enrolled. Liver stiffness was measured by using time-harmonic elastography based on externally induced continuous vibrations of 30 Hz to 60 Hz frequency and real-time B-mode-guided wave profile analysis covering tissue depths of up to 14 cm. The diagnostic accuracy of time-harmonic elastography in staging liver fibrosis was assessed with area under the receiver operating characteristic curve (AUC) analysis. Liver stiffness cutoffs for the differentiation of fibrosis stages were identified based on the highest Youden index. Results Time-harmonic elastography was feasible in all patients (0% failure rate), including 70% (n = 47) of individuals with extreme obesity (body mass index above the 99.5th percentile). AUC analysis for the detection of any fibrosis (≥ stage F1), moderate fibrosis (≥ stage F2), and advanced fibrosis (≥ stage F3) was 0.88 (95% confidence interval [CI]: 0.80, 0.96), 0.99 (95% CI: 0.98, 1.00), and 0.88 (95% CI: 0.80, 0.96), respectively. The best liver stiffness cutoffs were 1.52 m/sec for at least stage F1, 1.62 m/sec for at least stage F2, and 1.64 m/sec for at least stage F3. Conclusion US time-harmonic elastography allows accurate detection of moderate fibrosis even in pediatric patients with extreme obesity. Larger clinical trials are warranted to confirm the accuracy of US time-harmonic elastography.

Non‐invasive structure–function assessment of the liver by 2D time‐harmonic elastography and the dynamic Liver MAximum capacity (LiMAx) test

“…Our SWS values measured in healthy controls and patients without fibrosis agreed well with data reported by THE as well as with results obtained by multifrequency magnetic resonance elastography . THE values were described before to be independent from BMI and sex, which is confirmed by our data . Concerning liver function, median LiMAx values of our patient cohort were in the range of previous results .…”

“…However, both methods were limited in separating patients with no fibrosis from those with moderate fibrosis unlike reported for a cohort of obese adolescents with pediatric nonalcoholic fatty liver disease. 24 The ability of the LiMAx test to accurately diagnose different stages of liver fibrosis has recently been presented by Buechter et al 26 In their retrospective analysis of 102 patients with CLD, similar to our findings, clear decreasing tendencies of LiMAx values with increasing histological degrees of fibrosis, according to the Desmet & Scheuer scoring system, were observed. Furthermore, their AUROC analysis revealed that the LiMAx discriminated best between mild to moderate fibrosis (Desmet F0-3) and cirrhosis (Desmet F4) but less accurate between no and moderate fibrosis stages.…”

“…23 THE values were described before to be independent from BMI and sex, which is confirmed by our data. 24 Concerning liver function, median LiMAx values of our patient cohort were in the range of previous results. 11 Our LiMAx values did not depend on the patients' age, which is in line with previous reports, showing that neither age nor sex influences the LiMAx outcome.…”

“…THE and LiMAx were able to discriminate well between non‐severe and severe fibrosis (AUROC: THE 0.94; LiMAx 0.89). However, both methods were limited in separating patients with no fibrosis from those with moderate fibrosis unlike reported for a cohort of obese adolescents with pediatric non‐alcoholic fatty liver disease . The ability of the LiMAx test to accurately diagnose different stages of liver fibrosis has recently been presented by Buechter et al .…”

Die nicht-alkoholische Fettlebererkrankung bei Kindern und Jugendlichen – ein Update

“…Fibrose adäquat einzuschätzen. In der Bildgebung hat sich dabei die ultraschallbasierte Time-Harmonic Elastographie (THE) als vielversprechend in der Diagnostik einer relevanten Fibrose erwiesen [28]. Im Gegensatz zu bereits etablierten elastographischen Verfahren wie dem Fibroscan ® zeichnet sich die THE dadurch aus, dass eine Untersuchungstiefe von bis zu 14 cm möglich ist und dieses Verfahren somit auch für Patienten mit extremer Adipositas geeignet ist.…”