Increased liver stiffness and activated hepatic stellate cells in acute liver failure

Introduction: Acute liver failure (ALF) is associated with massive short term cell death, while 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 unclarified.

Methods: Twenty-nine patients (median age=43yrs.; 17 females/12 males) with ALF according to the ALFSG criteria were included. Upon diagnosis of ALF, as well as after 7 days, we determined hepatic elasticity (LS) by FibroScan®, standard laboratory parameters, serum levels of matrix metalloproteinases (MMP-1, -2, -9), tissue inhibitors of metalloproteinases (TIMP-1, -2), hyaluronic acid, markers of overall cell death (M65), and apoptosis (M30). Stellate-cell activation was analyzed immunohistochemically in biopsies of 12 patients by alpha-SMA staining.

Results: Cell death (M30: 2243±559.6U/l; M65: 3732±839.9U/l) as well as fibrosis markers (TIMP-1: 629.9±69.4U/ml; MMP-2: 264±32.5U/ml; hyaluronic acid: 438.5±69.3µg/ml) were significantly increased in patients compared to healthy controls. This was paralleled by collagen deposition, elevated alpha-SMA expression and higher LS (25.6±3.0kPa). Dividing the patients into two groups according to increasing (+10.2±3.23kPa; group1; n=11) or decreasing LS (–13.4±3.4kPa; group2; n=16) exhibited significantly increased M65 and TIMP-1 (6657.2U/ml vs. 2736.7U/ml, p=0.029; 737.3U/ml vs. 304.1U/ml, p=0.0011), accompanied by higher HSC activity (median score 6.5 vs. 2; p=0.028) in group1.

Conclusion: Our results demonstrate evidence of HSC activation in ALF. Positive correlation between LS, the degree of liver-cell damage and the intensity of HSC activation suggest that mild fibrosis might be necessary for timely recovery of ALF patients. Moreover, Fibroscan® may serve as an additional easily accessible parameter to assist in predicting the outcome of ALF.