title: Acute liver failure is associated with elevated liver stiffness and hepatic stellate cell activation.
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 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 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 microg/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dechêne
authors.forename: Jan-Peter
authors.initials: JP
authors.lastname: Sowa
authors.forename: Robert K
authors.initials: RK
authors.lastname: Gieseler
authors.forename: Christoph
authors.initials: C
authors.lastname: Jochum
authors.forename: Lars P
authors.initials: LP
authors.lastname: Bechmann
authors.forename: Amr
authors.initials: A
authors.lastname: El Fouly
authors.forename: Martin
authors.initials: M
authors.lastname: Schlattjan
authors.forename: Fuat
authors.initials: F
authors.lastname: Saner
authors.forename: Hideo A
authors.initials: HA
authors.lastname: Baba
authors.forename: Andreas
authors.initials: A
authors.lastname: Paul
authors.forename: Volker
authors.initials: V
authors.lastname: Dries
authors.forename: Margarethe
authors.initials: M
authors.lastname: Odenthal
authors.forename: Guido
authors.initials: G
authors.lastname: Gerken
authors.forename: Scott L
authors.initials: SL
authors.lastname: Friedman
authors.forename: Ali
authors.initials: A
authors.lastname: Canbay
mesh_terms: D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016923:Cell Death; D004548:Elasticity / Q000502:physiology*; D005109:Extracellular Matrix / Q000473:pathology; D005260:Female; D055166:Hepatic Stellate Cells / Q000473:pathology*; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000473:pathology* / Q000503:physiopathology*; D017114:Liver Failure, Acute / Q000097:blood / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood; D008875:Middle Aged; D012189:Retrospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood
chemical_list: D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D006820:Hyaluronic Acid; D020782:Matrix Metalloproteinases