Acute Liver Failure Is Associated With Elevated Liver Stiffness and Hepatic Stellate Cell Activation
Acute Liver Failure Is Associated With Elevated Liver Stiffness and Hepatic Stellate Cell Activation
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DOI：
10.1002/hep.23754
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发表时间：
2010-09-01
期刊：
影响因子：
13.5
通讯作者：
Canbay, Ali
中科院分区：
文献类型：
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作者：
Dechene, Alexander;Sowa, Jan-Peter;Canbay, Ali
急性肝衰竭（ALF）与大量的短期细胞死亡有关，而慢性肝损伤伴随着持续的细胞死亡。肝星状细胞（HSC）有助于慢性肝损伤的组织修复和肝纤维化，尽管它们在ALF中的作用仍然没有解释。根据急性肝衰竭研究组标准，纳入了29例ALF患者（中位年龄= 43岁，17例女性和12例男性）。在诊断ALF后7天，我们用Fibro-Scan测定肝硬度（LS）、标准实验室参数、血清基质金属蛋白酶1（MMP-1）、MMP-2、MMP-9、金属蛋白酶组织抑制剂1（TIMP-1）、TIMP-2、透明质酸和总细胞死亡（M65）和凋亡（M30）标志物水平。分别用α-平滑肌肌动蛋白（α-SMA）、角蛋白-17和角蛋白-19染色对12例患者的活检样本中的星状细胞活化和祖细胞反应进行免疫化学分析。细胞死亡标志物（M30水平= 2243 +/- 559.6 U/L，M65水平= 3732 +/- 839.9 U/L）和纤维化标志物（TIMP-1水平= 629.9 +/- 69.4 U/mL，MMP-2水平= 264 +/- 32.5 U/mL，透明质酸水平= 438.5 +/- 69.3 μ g/mL）在患者中相对于健康对照显著增加。胶原沉积、α-SMA表达升高和LS较高（25.6 +/- 3.0 kPa）导致了这一结果。ALF与导管祖细胞增殖有关。结论：我们的研究结果表明，肝硬化激活和祖细胞反应在ALE。LS、肝细胞损伤程度和HSC活化强度之间的正相关性表明，纤维化是对ALF试图修复受损组织的反应。（肝脏学2010;52：1008-1016）
Acute liver failure (ALF) is associated with massive short-term cell death, whereas chronic liver injury is accompanied by continuous cell death. Hepatic stellate cells (HSCs) contribute to tissue repair and liver fibrosis in chronic liver injury, although their role in ALF remains unexplained. Twenty-nine patients (median age = 43 years, 17 females and 12 males) with ALF according to the Acute Liver Failure Study Group criteria were included. Upon the diagnosis of ALF and after 7 days, we determined liver stiffness (LS) with Fibro-Scan, standard laboratory parameters, and serum levels of matrix metalloproteinase 1 (MMP-1), MMP-2, MMP-9, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, hyaluronic acid, and markers of overall cell death (M65) and apoptosis (M30). Stellate cell activation and progenitor response were analyzed immunohistochemically in biopsy samples of 12 patients with alpha-smooth muscle actin (alpha-SMA), keratin-17, and keratin-19 staining, respectively. Cell death markers (M30 level = 2243 +/- 559.6 U/L, M65 level = 3732 +/- 839.9 U/L) and fibrosis markers (TIMP-1 level = 629.9 +/- 69.4 U/mL, MMP-2 level = 264 +/- 32.5 U/mL, hyaluronic acid level = 438.5 +/- 69.3 mu g/mL) were significantly increased in patients versus healthy controls. This was paralleled by collagen deposition, elevated alpha-SMA expression, and higher LS (25.6 +/- 3.0 kPa). ALF was associated with ductular progenitor proliferation. Conclusion: Our results demonstrate HSC activation and a progenitor response in ALE. Positive correlations between LS, the degree of liver cell damage, and the intensity of HSC activation suggest that fibrosis is a response to ALF in an attempt to repair damaged tissue. (HEPATOLOGY 2010;52:1008-1016)