Mosca Antonella, Braghini Maria Rita, Andolina Giulia, De Stefanis Cristiano, Cesarini Lucia, Pastore Anna, Comparcola Donatella, Monti Lidia, Francalanci Paola, Balsano Clara, Pietrobattista Andrea, Alisi Anna, Panera Nadia
Hepatology and Liver Transplant Unit, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
Research Unit of Genetics of Complex Phenotypes, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
Int J Mol Sci. 2025 Jul 5;26(13):6486. doi: 10.3390/ijms26136486.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic progressive hepatopathy in children, and the identification of non-invasive biomarkers is urgently needed. Growth differentiation factor 15 (GDF15) was associated with MASLD in adults. In this study, we investigated the circulating and hepatic levels of GDF15 and their association with liver damage in pediatric MASLD and in a murine model. This observational study included 158 children with biopsy-proven MASLD. Patients with MASLD were categorized into two groups based on steatohepatitis (MASH) presence and evaluated for GDF15 circulating levels, while GDF15 hepatic levels were assessed only in a subset of patients. Children with MASLD exhibited higher levels of circulating GDF15 compared to the controls. Moreover, the MASH subgroup had significantly higher values of GDF15 compared to the Not-MASH subgroup. The GDF15 levels in the MASH subgroup showed a positive correlation with fibrosis. Finally, the hepatic expression of the GDF15 gene correlated with GDF15 circulating levels and with the hepatic expression of the COL1A1 and COL3A1 genes in 15 children with MASLD. In conclusion, our study demonstrated that GDF15 levels are associated with liver damage, reinforcing the potential role of GDF15 as a biomarker for MASLD-related fibrosis in children.
代谢功能障碍相关脂肪性肝病（MASLD）是儿童中最常见的慢性进行性肝病，因此迫切需要鉴定非侵入性生物标志物。生长分化因子15（GDF15）与成人MASLD相关。在本研究中，我们调查了儿童MASLD及小鼠模型中GDF15的循环水平和肝脏水平及其与肝损伤的关系。这项观察性研究纳入了158例经活检证实为MASLD的儿童。根据是否存在脂肪性肝炎（MASH）将MASLD患者分为两组，并评估其GDF15循环水平，而仅在部分患者中评估GDF15肝脏水平。与对照组相比，MASLD儿童的循环GDF15水平更高。此外，与非MASH亚组相比，MASH亚组的GDF15值显著更高。MASH亚组中的GDF15水平与纤维化呈正相关。最后，在15例MASLD儿童中，GDF15基因的肝脏表达与GDF15循环水平以及COL1A1和COL3A1基因的肝脏表达相关。总之，我们的研究表明GDF15水平与肝损伤相关，强化了GDF15作为儿童MASLD相关纤维化生物标志物的潜在作用。
