Serum LEAP-2 as a Potential Biomarker for Hepatic Steatosis in Adolescents with Obesity and MASLD: A Cross-Sectional Study

<b>Background/Objectives:</b> Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming more common among adolescents, but non-invasive biomarkers for early detection are still limited. Liver-expressed antimicrobial peptide-2 (LEAP-2), a ghrelin receptor antagonist, has been connected to obesity and liver fat buildup in adults, but pediatric data are limited. This study investigates the hypothesis that higher levels of LEAP-2 are associated with hepatic steatosis and the role of LEAP-2 serum levels in the earlier and easier diagnosis of MASLD in children. <b>Methods:</b> In this cross-sectional study, 51 adolescents aged 12-18 were divided into three groups: one with MASLD and obesity (MASLD-Ob) (confirmed hepatosteatosis by imaging studies such as magnetic resonance or ultrasound, along with at least one cardiometabolic criterion and a body mass index (BMI) > 2 SD) (<i>n</i> = 19), another with obesity without any liver pathology or MASLD (BMI > 2 SD) (<i>n</i> = 14), and healthy controls (<i>n</i> = 18). The controlled attenuation parameter (CAP) was measured using FibroScan^® Mini + 430 (Echosens SA, Créteil, France), and serum ghrelin and LEAP-2 levels were determined via ELISA. Correlations between LEAP-2, ghrelin, CAP, BMI z-score, and metabolic parameters were analyzed. <b>Results:</b> LEAP-2 and ghrelin levels among the three groups were similar (<i>p</i> = 0.148, <i>p</i> = 0.515). A positive correlation was observed between LEAP-2 levels and CAP values in the obese group (both the MASLD-Ob and obesity groups) (r = 0.379, <i>p</i> = 0.030). When a cutoff of 240 dB/m was used, the median LEAP-2 level in cases above this value was 2.20 ng/mL, compared to 1.37 ng/mL in cases below it (<i>p</i> = 0.021), which was significantly different. When analyzing the obese group (both the MASLD-Ob and obese groups) a statistically significant correlation was found between serum LEAP-2 levels and CAP, AST, GGT, and total bilirubin values (r = 0.379, <i>p</i> = 0.030; r = 0.369, <i>p</i> = 0.035; r = 0.369, <i>p</i> = 0.035; r = 0.357, <i>p</i> = 0.049, respectively). <b>Conclusions:</b> Interventional imaging methods and biomarkers for diagnosing and monitoring hepatosteatosis have become well-established in the literature. However, since these tests are not available at all centers and can be costly, there is an increasing search for other easily accessible diagnostic and follow-up parameters. LEAP-2 could be a promising non-invasive biomarker for pediatric MASLD, especially when used alongside CAP measurements. The application of this biomarker in pediatric MASLD provides valuable data to help identify and monitor the condition in adolescents. We believe our study offers strong evidence to support further research and the development of drug treatments for MASLD that aim to reduce plasma LEAP-2.