Liver death and regeneration in paracetamol toxicity
Liver death and regeneration in paracetamol toxicity
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DOI：
10.1191/0960327103ht325oa
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发表时间：
2003-04-01
影响因子：
2.8
通讯作者：
Harrison, DJ
中科院分区：
文献类型：
--
作者：
McGregor, A;More, LJ;Harrison, DJ
在英国和美国，扑热息痛过量（POD）是一个主要的临床问题，是暴发性肝衰竭（FHF）的最常见原因。虽然肝脏质量的主要损失发生在肝细胞坏死后，但据报告，在小鼠肝脏中对乙酰氨基酚毒性期间也发生了肝细胞凋亡。先前未在人肝脏中发现肝细胞凋亡，且尚不清楚对乙酰氨基酚毒性中细胞凋亡的意义。在POD后对乙酰氨基酚对人肝脏毒性的这项研究中，在肝移植或死亡时发现了肝细胞凋亡，并与显著的再生活性相关。细胞凋亡的生物学意义尚不清楚，但发现的细胞凋亡率（0.6%）可以解释肝实质的显着损失。细胞凋亡的刺激尚不清楚，但不太可能直接由扑热息痛诱导。因为此时血清中不存在它。细胞凋亡可能是由枯否细胞活化和细胞因子产生诱导的。POD后发生FHF的患者预后不良，除肝移植外几乎没有治疗选择;对肝再生动力学和细胞凋亡导致的持续细胞丢失的理解可能有助于开发这些患者的新疗法。
Paracetamol overdose (POD) is a major clinical problem as the commonest cause of fulminant hepatic failure (FHF) in the UK and the USA. While the main loss of liver mass occurs following hepatocyte necrosis, hepatocyte apoptosis has also been reported to occur during paracetamol toxicity in murine liver. Hepatocyte apoptosis has not previously been identified in human liver and the significance of apoptosis in paracetamol toxicity is not known. In this study of paracetamol toxicity in human liver after POD, hepatocyte apoptosis was identified at time of liver transplantation or death and was associated with striking regenerative activity. The biological significance of apoptosis is unclear but the rates of apoptosis found (0.6%) could account for a significant loss of hepatic parenchyma. The stimulus for apoptosis is not known but it is unlikely to be induced directly by paracetamol. since it is absent from serum at this time. The possibility that apoptosis may be induced by Kupffer cell activation with cytokine production is raised. Patients who develop FHF after POD have a poor prognosis, with few therapeutic options apart from liver transplantation; an understanding of the dynamics of liver regeneration and ongoing cell loss by apoptosis may allow the development of new therapies in these patients.