Acute liver failure is associated with elevated liver stiffness and hepatic stellate cell activation
| Autor: | M Odenthal, Robert K. Gieseler, Alexander Dechêne, Ali Canbay, Guido Gerken, Scott L. Friedman, Fuat H. Saner, Lars P. Bechmann, Christoph Jochum, Volker Dries, Martin Schlattjan, Andreas Paul, Hideo A. Baba, Jan-Peter Sowa, Amr El Fouly |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Adult
Liver Cirrhosis Male medicine.medical_specialty Programmed cell death Pathology Biopsy Medizin Apoptosis Extracellular matrix Fibrosis Internal medicine Hepatic Stellate Cells medicine Humans Hyaluronic Acid Retrospective Studies Tissue Inhibitor of Metalloproteinase-2 Tissue Inhibitor of Metalloproteinase-1 Cell Death Hepatology medicine.diagnostic_test business.industry Liver Failure Acute Middle Aged medicine.disease Hepatic stellate cell activation Elasticity Matrix Metalloproteinases Extracellular Matrix Endocrinology Liver Hepatic stellate cell Female business Biomarkers |
| Zdroj: | Hepatology. 52:1008-1016 |
| ISSN: | 0270-9139 |
| DOI: | 10.1002/hep.23754 |
| Popis: | 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) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text