丰坦手术是一种针对单心室先天性心脏病的重建手术。该手术通常在儿童早期进行,通常会导致多种内脏器官并发症,包括肝纤维化或丰坦相关性肝病(FALD)。然而,FALD的潜在机制尚不清楚,而且被认为有别于其他形式的肝纤维化疾病。最近的一项研究在单细胞水平上生成了人类FALD的转录组和表观基因组图谱,为FALD的发病机制提供了重要见解。在Fontan循环患者(n = 4,2-3岁时接受Fontan手术,13-18岁时作为青少年获得肝活检样本)肝脏的各种细胞类型中观察到了深刻的转录组和表观基因组变化。值得注意的是,中央肝细胞的变化最为显著,包括代谢重编程。这些中央肝细胞的变化先于肝星状细胞的激活和肝纤维化。研究还发现了一个配体-受体网络,该网络参与了从中央肝细胞到肝星状细胞的信号传导,体外研究表明,激活素 A 和 B 促进了肝纤维化的激活。
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