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 5 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 a-smooth muscle actin (a-SMA), keratin-17, and keratin-19 staining, respectively. Cell death markers (M30 level 5 2243 6 559.6 U/L, M65 level 5 3732 6 839.9 U/L) and fibrosis markers (TIMP-1 level 5 629.9 6 69.4 U/mL, MMP-2 level 5 264 6 32.5 U/mL, hyaluronic acid level 5 438.5 6 69.3 lg/mL) were significantly increased in patients versus healthy controls. This was paralleled by collagen deposition, elevated a-SMA expression, and higher LS (25.6 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;52:1008-1016 A cute liver failure (ALF) is a devastating clinical syndrome associated with high mortality in the absence of immediate state-of-the-art intensive care or liver transplantation. 1 ALF can occur as a result of various etiologies (overdosing with acetaminophen or other drugs, viral hepatitis, ischemia, and other causes 1 ); in approximately 15% of adult cases and 50% of pediatric cases, the reason is unidentified. 2
ABSTRACT.Purpose: We evaluated the relationship between ocular surface damage, elevated lid aperture/impaired Bell's phenomenon and reduced tear production in thyroidassociated ophthalmopathy (TAO). Suspecting a possible role of autoantibodies specific for TSH receptor (TSHR), we further investigated TSHR expression in the healthy lacrimal gland (LG). . We firstly demonstrate that lacrimal acinar cells physiologically express TSHR. Conclusions: As ocular surface damage in TAO significantly correlates with reduced tear production, LG impairment appears to be a major cause of ocular surface drying. Intriguingly, physiological expression of TSHR by LG suggests that, in thyroid disease, autoantibodies may bind to lacrimal TSHR and, perhaps via aberrant signal transduction, contribute to LG impairment and, hence, dry eye syndrome.
VD may be an antifibrotic treatment option early in the onset of fibrosis in specific genotypes for VDR. Known polymorphisms of the VDR may influence the response to VD treatment.
To investigate the differentiation and activation of monocytes, the combined effects of 1,25-dihydroxyvitamin D3 (D3) and IL-4 on human blood monocytes were examined with respect to expression of MHC class-II antigens, accessory activity, and phagocytic capacity. IL-4 was reported to upregulate the expression of MHC class-II antigens and accessory activity of monocytes. The experiments described here demonstrate that D3 inhibits the expression of all three subtypes of MHC class-II antigens (HLA-DR, -DP and -DQ) as well as the accessory activity of monocytes, both in a dose- and time-dependent manner. However, D3 enhances the immunoglobulin- and complement-dependent phagocytosis by monocytes in a dose- and time-dependent manner. When monocytes are treated with both IL-4 and D3, the effects of D3 are reverted by IL-4, suggesting that IL-4 induces the development of monocytes into accessory cells, whereas D3 stimulates differentiation of monocytes into classical macrophages. These findings provide further evidence for the contention that, depending on defined stimuli, monocytes may develop either into accessory cells or into classical macrophages.
Liver transplantation in cirrhotic patients is accompanied by severe bleeding. Indeed, the first 100 recipients of liver allografts transplanted by Thomas E. Starzl died mainly by uncontrolled bleeding. Since then, much progress has been made as to the understanding of the pathophysiology and the treatment of hemostatic disorders in cirrhotic patients. The aim of this review is to provide a state-of-the-art overview on recent developments and treatment options for hemostatic disorder in cirrhotic patients. Patients with end-stage-liver disease (ESLD) do not suffer only from procoagulant deficiency; there is also a lack of natural anticoagulants (i.e. proteins C and S) and profibrinolytics. Conventional laboratory methods such as the determination of the international normalized ratio or the activated partial thromboplastin time cannot predict bleeding complications in these patients. Progressive diagnostic techniques reveal that cirrhotic patients have the same capacity to produce thrombin like healthy volunteers. Moreover, cirrhotic patients - and particularly those with primary biliary cirrhosis or primary sclerosing cholangitis - are at a higher risk for developing thrombosis as compared with healthy controls. Hemostatic alterations are common in cirrhotic patients; they involve both the pro- and the anticoagulant pathways. However, this is a very delicate balance, which may be shifted to either of these pathways by different treatments thereby causing bleeding or thrombosis, respectively.
Stress-induced soluble major histocompatibility complex class I-related chains A/B (MIC A/B) are increased in chronic liver diseases and hepatocellular malignancy. We investigated the impact of these molecules on liver injury, apoptosis, and fibrosis in nonalcoholic steatohepatitis (NASH). Blood and liver tissue were obtained from 40 patients with NASH undergoing bariatric surgery for obesity. The control group consisted of 10 healthy individuals. We also investigated 10 patients with nonalcoholic fatty liver (NAFL). Polymerase chain reaction was used to measure messenger RNA (
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