Biliary atresia and Cytokine

摘要本研究旨在探讨长期胆道闭锁（BA）患者在细胞因子网络控制方面的病理生理变化。在我们的研究中，血清IL-1或相关细胞因子和造血因子没有显示任何特异性变化来定义潜在的肝胆和脾病理。在众多细胞因子中，最近报道的血小板生成素（thrombopoietin， TPO）被认为与肝硬化相关的脾功能亢进和门静脉高压症密切相关。然而，血清TPO水平与血小板计数之间的相关性被证明是不显著的，这可能是因为血清TPO水平不仅仅依赖于血小板计数，特别是在慢性肝病患者中，而是主要由血小板计数增加或减少的相关因素决定的平衡状态。因此，当这些稳定的患者经历了实质性的压力，如脾功能亢的部分脾栓塞（PSE）或晚期肝硬化的活体相关肝移植（LRLTx）时，测定血清TPO的变化似乎有助于确定TPO的病理生理作用。血清TPO水平在PSE后3天达到峰值，血小板计数逐渐上升，在2周左右达到峰值。在接受LRTx的患者中，血清TPO在1周左右出现峰值，与TPO水平的阳性变化无关，血小板计数持续低水平。这些TPO和血小板计数变化的变化模式为确定TPO在包括BA在内的儿童肝脏慢性疾病中的生理作用提供了重要线索。

ABSTRACTThis study was undertaken to investigate pathophysiology of long-term biliary atresia (BA) patients in terms of alterations in cytokine network control. In our study, serum IL-1 or related cytokines, and hematopoietic factors did not reveal any specific changes to define underlying hepatobilary and splenic pathologies. Among many cytokines, thrombopoietin (TPO), a newly reported one, was expected to be deeply involved in hypersplenism associated with liver cirrhosis as well as portal hypertension. However, the correlation between serum TPO levels and platelet counts proved to be insignificant possibly because the serum TPO levels are not dependent on platelet counts alone especially in patients with chronic liver disorders, but are determined promarily by an equilibrium state based on relevant factors which increase or decrease blood platelet counts. Accordingly, it seemed helpful in defining pathophysiological roles of TPO to determine serum TPO changes when these stable patients undergo substantial stresses like partial splenic embolization (PSE) for hypersplenism or living-related liver transplantation (LRLTx) for advanced liver cirrhosis. Serum TPO levels peaked 3 days after PSE whereas platelet count rose gradually with a peak at around 2 weeks. In patients who underwent LRTx, serum TPO showed a peak value at around 1 week with persistent low levels of platelet count irrespective of positive changes of TPO levels. These varying patterns of TPO and platelet count changes offered an important clue to identify the physiological role of TPO in pediatric chronic diseases of the liver including BA.