As a multifactorial disease, obesity is considered a worldwide syndemic problem in all age groups, and a risk factor for several conditions, such as metabolic dysfunction associated with steatotic liver disease (MASLD) [1]. The high prevalence of both diseases has been driven by increased sedentary behavior, excessive calorie intake from unbalanced and unhealthy diets, socioeconomic status, and genetic and epigenetic factors [2]. It is noted that a recent meta-analysis reported that the prevalence of MASLD in children is between 5 % and 10 % in the general population, and can be detected in 47 % of children with obesity, mainly affecting boys [3].

Current understanding of MASLD (fatty infiltration in more than 5 % of hepatocytes) in the pediatric age group is that untreated metabolic dysfunction can lead to worsening liver injury. Similar to the disease trajectory observed in adults, without appropriate intervention, there is a risk of progression to steatohepatitis (MASH) with inflammation and fibrosis, and in late adolescence or early adulthood, developing cirrhosis [4]. Furthermore, MASLD is also related to the increased risk of cardiovascular diseases, nowadays the major cause of death in this group [5].

The pathogenesis of MASLD is multifactorial, including genetic and environmental factors such as diet with elevated content of refined sugar and saturated fat, which act together to increase hepatic fat deposition. The excess of fat stimulates mitochondrial dysfunction, induces oxidative stress, and apoptosis [6]. Beyond insulin resistance, the lipotoxicity due to obesity can also contribute to the development of liver inflammation. Furthermore, the local and systemic production of pro-inflammatory cytokines may play a key role in the progression to steatohepatitis [7].

The gold standard to diagnosing MASLD is the hepatic biopsy, which is difficult and stressful to perform in children. The hepatic transient elastography is a less invasive method that can analyze the presence of fibrosis (liver stiffness measurement or LSM) and steatosis (controlled attenuation parameter or CAP) [8]. It is well studied in the adult population, although pediatric data are scarce. Given this gap in the literature, the present study evaluated the possible differences in obesity markers and cardiovascular risk factors among children and adolescents with excess weight in the presence or absence of steatosis according to transient hepatic elastography, in addition to evaluating their correlation with CAP and LSM, and investigating possible biomarkers for MASLD.

The characteristics of the sample are presented in Table 1. The proportion of girls and boys was similar (19 female and 19 male). Participants mostly presented obesity (N = 28; 73.7 %), were already in puberty (N = 30; 78.9 %) and reported being moderately active (N = 22; 57.9 %).

Table 2 shows "Steatosis group" vs. “Non-Steatosis group" based on transient elastography analyses. Steatosis was classified according to the degree of involvement and CAP value: S3 (15.8 %. N = 6), S2 (18.4 %. N = 7) and S1 (2.7 %. N = 1). Pubertal status, sex and physical activity level were not different between groups. Obesity was present in all patients of the "Steatosis group" and in 60 % of "Non-Steatosis group". The presence of fibrosis was investigated by LSM and was detected in only three (7.9 %) participants of the "Steatosis group" (two staged as F2 and one as F3).

Adiponectin (cut-off ≤ 4.5 μg/mL) had a sensitivity of 85.7 % with a specificity of 79.2 %, while insulin (cut-off ≥ 22 mcUI/mL) had a sensitivity of 78.6 % with a specificity of 79.2 %. A minor discriminatory power was found for: leptin, a cut-off ≥ 36 ng/mL gives a sensitivity of 71.4 % and specificity of 66.7 %, and ALT, a cut-off was ≥ 24 UI/L, with sensibility of 78.6 % e specificity of 73.9 % (Figure 2).

Figure 2.

ROC curves for predict steatosis. (A) ROC curves for adiponectin. (B) ROC curves for insulin. (C) ROC curves for leptin. (D) ROC curves for ALT.

LSM correlated positively with serum levels of insulin, HOMA-IR and both CIMT. Anthropometric, blood pressure, basal insulin, HOMA-IR, leptin, hepatic markers (ALT and GGT) and abdominal fat distribution variables (SAT and VAT) showed positive associations with CAP, while adiponectin showed a negative correlation (Table 3).

This cross-sectional study evaluated differences in a pediatric age group with excess weight related to the presence or absence of MASLD according to transient hepatic elastography. Important metabolic profile differences were observed in patients with MASLD, and also significant correlations were found between the CAP and LSM values and cardiovascular risk factors. It is worth noting that the differences were observed despite both groups presenting patients with previous hepatic enzyme alterations and at high risk for MASLD.

The mean CAP values of the groups with and without steatosis were 288 and 170 dB/m, respectively, Desai et al. demonstrated, in a study where children underwent liver biopsy to confirm the diagnosis of steatosis, that a mean CAP value of 290 dB/m was found in the steatosis group and 198 dB/m for the non-steatosis [16].

There was a significant difference in the LSM patterns when comparing the groups with and without steatosis. Despite the few cases of fibrosis, LSM values correlated with cardiovascular risk factors related to obesity. These results were also found by Gong et al. [17]. and indicate the worsening of the health conditions of these patients related to obesity.

Anthropometric measurements are easy and quick to apply and are considered a good cardiometabolic risk screening, in addition to being related to MASLD [18]. This data support this concept, since the "Steatosis group" was mostly classified as severely obese, and there was a positive association between CAP values (but not with LSM) and anthropometric parameters.

Dysfunctional glucose metabolism plays a key role in the pathophysiology of MASLD [19]. Along with obesity and high triglyceride (TG) levels, a feedback system involving these factors is observed in both adults and children [20]. The present data showed a weak correlation between TG and CAP, higher fasting insulin levels, and greater HOMA-IR values in the "Steatosis group". Unlike Ting et al., who correlated HOMA-IR only with fibrosis [21], the authors found a correlation between insulin resistance markers and both LSM (weak) and CAP values (moderate).

The excess of visceral fat can be considered an important predictor of metabolic syndrome, MASLD, and increased risk for cardiovascular diseases. Despite no consensus for cutoff values to classify cardiovascular risk in children, it is well established that a higher intra-abdominal fat is associated with greater insulin resistance, therefore, the possible presence of MASLD [22]. The present data points in the same direction, as they showed a positive correlation between CAP values and both subcutaneous (SAT) and visceral fat (VAT) indices.

Hypertension can be considered an intersection point between MASLD and metabolic syndrome. A cross-sectional study with a population database demonstrated a link between steatosis through the Hepatic Steatosis Index (HSI), and hypertension in adults [23]. Similar findings were present in this study, with a moderate correlation between CAP levels and SBP Z-score, a supported result of steatosis and cardiovascular risk. Children of the “Steatosis group” could already be investigated for hypertension due to altered BP behavior, which reinforces the need for long-term arterial monitoring of such patients.

Studies describing the association between the results of transient elastography and CIMT are scarce in the literature. However, a cross-sectional study with 96 patients of a specialized medicine center in Italy stated an elevated risk of atherosclerotic disease in patients with fibrosis [24]. This data agrees with the present study, which showed a slightly greater right CIMT in the “Steatosis group” and a positive association was found between LSM and both CIMT.

Adiponectin is recognized as a hormone that plays an important role in regulating homeostasis in healthy individuals. At lower levels, it is associated with metabolic dysfunctions such as obesity and the progression of MASLD, a scenario that can also be observed in children. In the same context, low leptin levels are correlated with appetite regulation and progression of obesity [25,26,27]. Although no studies were found evaluating the relationship between transient elastography and adipokines in children and adolescents, in the present study, CAP values demonstrated moderate correlations, negative with adiponectin and positive with leptin.

The measurement of ALT is used worldwide as a screening for many liver diseases, including MASLD, and can also be related to the severity of the disease. Schwimmer et al. showed that ALT was higher in patients with MASLD when compared to other liver diseases or the control group, being even greater in those with steatohepatitis [28]. To predict the risk of simple steatosis, ROC curves presented the cut-off value of ≥ 22 mcUI/mL to insulin and ≥ 24 IU/L to ALT, for boys and girls.

About the ROC curves for adiponectin and leptin, Boyraz et al. failed to predict the presence or absence of MASLD, according to leptin, but suggested a cut-off value of < 3.2 µg/mL to predict steatosis [29], a value less than ≤ 4.5 µg/mL found in the present study. On the other hand, Manco et al. were able to use leptin and TNF-α as predictors of steatohepatitis in children but did not compare groups with or without simple steatosis [30].

The main limitation of the study was that a liver biopsy was not performed to confirm the diagnosis of MASLD, but it is an invasive test and carries a risk of complications. Although transient elastography is not the gold standard for diagnosing steatosis and fibrosis, many references have considered it a reliable and painless tool for diagnosing and evaluating these conditions in children, viable in research and clinical practice. Another limitation was the small number of participants included, which made it impossible to stratify and evaluate participants by pubertal stage.

On the other hand, transient elastography findings could be compared with several other variables evaluated in MASLD disease, and cross-sectional studies that associate specific parameters of pediatric patients with severe obesity and transient elastography measures (CAP and LSM) are scarce in the literature.

In school-age children and adolescents with excess weight, the presence of steatosis by elastography is related to elevated blood pressure, abdominal obesity, and worse glycemic and hepatic profiles. Furthermore, the present data suggest that low adiponectin and high basal insulin levels are possible biomarkers of MASLD. The study reinforces the need for children with obesity, especially those with a worse metabolic profile, to be investigated for early diagnosis, monitoring, and treatment of MASLD. Further research is needed to confirm these results.

This study was partially funded by grants from the Carlos Chagas Filho Foundation for Research Support in the State of Rio de Janeiro (FAPERJ) (APQ1 E-26–111,344-2014, E-26/ 202.866/2015, and E26–201.014–2022, recipient P.S.).

The data that support the findings of this study are available from the corresponding author.