Acute Liver Failure Is Associated With Elevated Liver Stiffness and Hepatic Stellate Cell Activation

作者：Dechene Alexander; Sowa Jan Peter; Gieseler Robert K; Jochum Christoph; Bechmann Lars P; El Fouly Amr; Schlattjan Martin; Saner Fuat; Baba Hideo A; Paul Andreas; Dries Volker; Odenthal Margarethe; Gerken Guido; Friedman Scott L; Canbay Ali^*

来源：Hepatology, 2010, 52(3): 1008-1016.

DOI：10.1002/hep.23754

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)

• 出版日期2010-9