## 3 The Opportunities and Challenges of Ultrasound-Based Elastography in Children NAFLD  
Liver fibrosis in pediatric patients is commonly seen in the setting of fatty liver disease, hepatitis, primary sclerosing cholangitis, autoimmune hepatitis, congestive hepatopathy, cystic fibrosis, biliary atresia, Alagille syndrome, Fontan-associated liver disease, a-1 antitrypsin deficiency, storage disorders, and Wilson's disease [36; 60]. Nevertheless, as we already mentioned, NAFLD has become one of the most common causes of chronic liver disease in pediatric populations due to the alarmingly persistent increasing incidence of obesity worldwide. Liver fibrosis is a common pathogenic feature of the above mentioned conditions and its assessment is extremely important in order to provide risk stratification, to guide therapeutic decision, and most important to monitor disease severity [26]. Taking into account the relatively low cost, the lack of invasive approach, no need for sedation, elastography might be a reliable alternative for the assessment of liver fibrosis. The importance of elastography methods for assessing liver fibrosis in adult patients is definitely incontestable, but in pediatric populations several challenges are related especially to their age-specific low compliance, resulting in possible invalid elastography measurement (Figures 3 and 4). Multiple confounding factors identified in pediatric populations were reported to influence liver stiffness on elastography, such as age, sedation, hepatic steatosis, or inflammation [64; 65]. Hepatic congestion and inflammation, commonly seen in patients with congenital heart diseases and inflammatory liver disorders, might also result in increased liver stiffness unassociated with fibrosis [36; 66]. Multiple studies revealed an increase in liver stiffness with age, but the results remain controversial since the association was found to be weak [64; 67; 68; 69; 70]. Thus, [PERSON] et al. proved a strong association between increasing age and liver stiffness measurements in children \(\geq\)3 years [64]. It is most likely that these findings might be related to microstructure, vascular, and metabolic changes that occur during maturation as it was proved on animal models [71; 72]. Similar trends were noticed by [PERSON] et al. in a study performed on 123 children using TE, who found a liver stiffness value of 3.4 kPa between 1-5 years of age, 3.8 kPa in children aged 6 to 11 years, and 4.1 kPa in those aged 12 to 18 [73]. In addition, a study performed on 206 normal weight healthy children assessing liver stiffness using both 2D SWE and TE identified an increase in elastography values on both methods directly related to the individual's age. This study pointed out that the cutoff values on 2D SWE ranged between 4.13 kPa in children aged between 3-5 years and 4.88 in those between 12 to 15; while on TE these values varied from 4.40 kPa between 3-5 years of age and 5.1 kPa in adolescents aged 15-18 years [74]. It is also worth mentioning that according to [PERSON] et al., liver stiffness values are not affected by either age or gender in children, who found a normal median liver stiffness value of 4.5 kPa in healthy children with no comorbidities, without assessing other laboratory parameters, such as serum liver enzymes or APRI [75]. Therefore, age represents a potential limitation as well as a challenge in the assessment of liver stiffness on elastography and it should be taken into account as a potential confounder in order to increase the accuracy of these methods.