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

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. Twen...

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Published in:Hepatology (Baltimore, Md.) Md.), 2010-09, Vol.52 (3), p.1008-1016
Main Authors: Dechêne, 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
Format: Article
Language:English
Subjects:
Adult
Apoptosis
Biological and medical sciences
Biomarkers - blood
Biopsy
Cell Death
Elasticity - physiology
Extracellular Matrix - pathology
Female
Gastroenterology. Liver. Pancreas. Abdomen
Hepatic Stellate Cells - pathology
Humans
Hyaluronic Acid - blood
Liver - pathology
Liver Cirrhosis - blood
Liver Cirrhosis - pathology
Liver Cirrhosis - physiopathology
Liver Failure, Acute - blood
Liver Failure, Acute - pathology
Liver Failure, Acute - physiopathology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Matrix Metalloproteinases - blood
Medical sciences
Middle Aged
Other diseases. Semiology
Retrospective Studies
Tissue Inhibitor of Metalloproteinase-1 - blood
Tissue Inhibitor of Metalloproteinase-2 - blood
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Summary: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 FibroScan, 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. (Hepatology 2010)
ISSN:0270-9139
1527-3350
DOI:10.1002/hep.23754