Acute liver failure is associated with elevated liver stiffness and hepatic stellate cell activation

Alexander Dechêne, Jan Peter Sowa, Robert K. Gieseler, Christoph Jochum, Lars P. Bechmann, Amr El Fouly, Martin Schlattjan, Fuat Saner, Hideo A. Baba, Andreas Paul, Volker Dries, Margarethe Odenthal, Guido Gerken, Scott L. Friedman, Ali Canbay

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

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 α-smooth muscle actin (α-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 μg/mL) were significantly increased in patients versus healthy controls. This was paralleled by collagen deposition, elevated α-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 ALF. 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.

Original languageEnglish
Pages (from-to)1008-1016
Number of pages9
JournalHepatology
Volume52
Issue number3
DOIs
StatePublished - Sep 2010

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