## 3 The Opportunities and Challenges of Ultrasound-Based Elastography in Children NAFLD
Taking into account the wide-spectrum of confounding factors identified in children with obesity, among which are obesity itself, fatty liver infiltration, a possible mild heart failure, and the incapacity to hold their breath, it is unsurprising that the reliability of elastography methods is closely related to body mass index [98], requiring the combination of these methods with other clinical and laboratory findings. In compliance to the above-mentioned facts, the study of [PERSON] et al. noticed that a body mass index greater than 35 in children might result in failure to obtain valid TE measurements [99]. This limitation is defined by the impact of skin-to-liver distance on the feasibility and accuracy of liver elastography. In terms of elastography, it was hypothesized that skin-to-liver distance \(<\) 34 mm is optimal for discriminating between fibrosis stages [100]. This hypothesis is in line with other studies which concluded that in patients with a BMI \(\geq\) 30 kg/m\({}^{2}\), elastography has a relatively low accuracy in differentiating between the first two fibrosis stages [101; 102]. It was also underlined that the success rate in obese patients depends on the technique being proved that TE has a higher failure rate in this group when compared to p-SWE [101]. Moreover, a recent study performed on obese adults emphasized that p-SWE is able to discriminate between fibrosis stages independently of its severity if skin-to-liver distance is taken into account following two rules: a thicker abdominal wall results in a lesser accuracy for a proper histological staging and the impact of skin-to-liver distance on accurate fibrosis staging is machine-dependent [103]. In terms of ARFI, it was showed that interoperator concordance increases when skin-to-liver distance is \(<\)2.5 cm [104], being previously documented that a higher concordance is reflected on the correlation between fibrosis stages assessed on ARFI and histology [105]. Using TE, another recent study proved that a skin capsular distance \(\geq\) 25 mm results in overestimation of fibrosis affecting the detection of severe fibrosis in patients with NAFLD [106]. Thus, this is an important challenge that should be addressed also in children with NAFLD since to date we found no study on this topic in pediatric patients with NAFLD. The accuracy of elastography methods might be improved if combined with other clinical or laboratory parameters in order to face the aforementioned challenges/limitations. A recent review which included 27 articles underlined that elastography is a reliable method in diagnosing liver fibrosis and cirrhosis in pediatric patients, whose accuracy is improved when used in combination with other clinical tools, such as serum markers [107]. Previous studies revealed positive associations between ultrasound-based elastography methods and several laboratory parameters such as ALT, APRI, or AST/ALT ratio (AAR), which are well-known to be increased in children with obesity [18; 19; 108]. The study of [PERSON] et al. used ARFI in combination with serum liver enzymes and triglyceride values and proved that liver stiffness is significantly correlated with liver enzymes and most children identified with a value above 1.19 m/s associated AAR > 0.8, defined also as a potential indicator of steatohepatitis [109]. Therefore, the combination between these laboratory parameters and elastography values might increase the accuracy in detecting and staging liver fibrosis in children with obesity. Multiple studies aimed to compare the performance of ultrasound-based elastography methods in NAFLD patients. [PERSON] et al. stated after reviewing 12 articles that fibrosis in children can be predicted with a higher sensitivity and specificity using supersonic shear imaging in comparison with ARFI, with an increasing accuracy in the setting of advanced fibrosis. The authors pointed out that the reference values according to ARFI are 1.34 m/s in case of stage 1 fibrosis, 1.57 m/s in stage 2, 1.85 m/s for stage 3, and 2.13 m/s for stage 4.