Circulating apoptotic and necrotic cell death markers in patients with acute liver injury
Circulating apoptotic and necrotic cell death markers in patients with acute liver injury
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DOI：
10.1111/j.1478-3231.2011.02528.x
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发表时间：
2011-09-01
影响因子：
6.7
通讯作者：
Simpson, Kenneth J.
中科院分区：
文献类型：
--
作者：
Craig, Darren G. N.;Lee, Patricia;Simpson, Kenneth J.
背景资料：宿主对细胞死亡的反应是急性肝损伤后免疫激活的基础，因此，对循环细胞死亡标志物的测量有助于对乙酰氨基酚过量后的诊断。细胞凋亡过程中形成的核小体可与高迁移率族蛋白1（HMGB 1）复合，在肝损伤中可能发挥致病作用。目的：探讨急性肝损伤后核小体、高迁移率族蛋白1（HMGB 1）和其他细胞死亡标志物的水平及其预后意义。研究方法：采用免疫分析法测定了33例对乙酰氨基酚和非对乙酰氨基酚诱导的急性肝损伤患者的血浆核小体、HMGB 1、半胱天冬酶切割的细胞角蛋白-18（M30）和总细胞角蛋白-18（M65）水平。结果如下：对乙酰氨基酚过量患者的入院核小体水平显著高于慢性肝病和健康对照受试者，但对乙酰氨基酚和非对乙酰氨基酚患者相似（P = 0.11）。在对乙酰氨基酚患者中，核小体水平与死亡或需要肝移植、符合不良预后标准或器官衰竭无关。核小体水平与HMGB 1（r = 0.500，P = 0.009）、丙氨酸氨基转移酶（r = 0.410，P = 0.038）和M65（r = 0.709，P < 0.001）相关，但与M30（r = 0.309，P = 0.124）无关。分析的细胞死亡标志物均未改善对乙酰氨基酚患者的凝血功能，超出国王学院标准。结论：急性肝损伤后血浆核小体明显升高。凋亡和坏死细胞死亡标志物均不能准确预测扑热息痛诱导的肝毒性后的存活率，这表明细胞死亡的程度和类型在决定结果方面发挥的作用有限。
Background: The host response to cell death underpins the immune activation that follows acute liver injury, and measurement of circulating cell death markers could therefore aid prognostication following paracetamol overdose. Nucleosomes, formed during apoptosis, can complex with high-mobility group box 1 (HMGB1) protein and may play a pathogenic role in liver injury. Aims: To explore the levels and prognostic significance of nucleosomes, HMGB1, and other cell death markers following acute liver injury. Methods: Levels of plasma nucleosomes, HMGB1, caspase-cleaved cytokeratin-18 (M30) and total cytokeratin-18 (M65) were measured by immunoassay, in a cohort of 33 patients with paracetamol-and nonparacetamol-induced acute liver injury. Results: Admission nucleosome levels in paracetamol overdose patients were significantly higher than in chronic liver disease and healthy control subjects, but were similar in paracetamol and non-paracetamol patients (P = 0.11). Nucleosome levels were not associated with death or requirement for liver transplantation, fulfillment of poor prognostic criteria or organ failure in paracetamol patients. Nucleosome levels correlated with levels of HMGB1 (r = 0.500, P = 0.009), alanine aminotransferase (r = 0.410, P = 0.038) and M65 (r = 0.709, P < 0.001), but not with M30 (r = 0.309, P = 0.124). None of the cell death markers analysed improved prognostication in paracetamol patients beyond the King's College criteria. Conclusions: Plasma nucleosomes are significantly elevated following acute liver injury. Neither apoptotic nor necrotic cell death markers accurately predict survival following paracetamol-induced hepatotoxicity, suggesting that the extent and type of cell death play a limited role in determining outcome.