ABSTRACT
BACKGROUND AND AIM: Accurate quantification of progressive liver disease is essential for therapeutic decisions and follow-up for patients who underwent liver transplantation. To evaluate the quality of noninvasive assessment of liver fibrosis in these patients, we compared Doppler ultrasound of the hepatic blood vessels as well as transient elastography (TE, FibroScan(®)) with liver biopsy following transplantation. METHODS: We performed Doppler ultrasound of the hepatic veins, hepatic artery, and portal vein as well as a TE in 48 patients who underwent liver transplantation 12 months ago. Hepatic venous flow was evaluated by determination of the resistance index (HVRI) of the right hepatic vein. Doppler and TE results were compared with histopathologic workup of a 12-month protocol liver biopsy after transplantation. RESULTS: HVRI showed a high reliability in predicting liver fibrosis stage FII or higher (AUROC of 0.99 ± 0.001 for FII or higher, the HVRI < 1.05 with a sensitivity and specificity of 100 and 91.43 %) compared to histopathologic workup (Desmet's score) and was comparable to TE analysis. Both HVRI and TE differed significantly in no or minimal fibrosis versus FII or higher (p < 0.001). In contrast, portal vein and hepatic artery did not show significant changes in blood flow in our study population. CONCLUSIONS: Hepatic vein flow resistance index is a valuable tool in noninvasive evaluation of liver fibrosis in liver transplantation follow-up predicting FII or higher and might help reducing the number of protocol biopsies needed.
Subject(s)
Elasticity Imaging Techniques , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/pathology , Liver/pathology , Ultrasonography, Doppler , Vascular Resistance , Adult , Aged , Area Under Curve , Biopsy , Female , Hepatic Artery/diagnostic imaging , Hepatic Artery/physiopathology , Hepatic Veins/diagnostic imaging , Hepatic Veins/physiopathology , Humans , Liver Cirrhosis/physiopathology , Liver Transplantation , Male , Middle Aged , Portal Vein/diagnostic imaging , Portal Vein/physiopathology , Predictive Value of Tests , Prospective Studies , ROC CurveABSTRACT
IL-6/gp130 dependent signaling plays an important role in modulating inflammation in acute and chronic diseases. The course of Concanavalin A- (Con A) induced hepatitis can be modulated by different immune-mediated mechanisms. IL-6/gp130-dependent signaling has been shown to be protective in hepatocytes. However, the role of this pathway in myeloid cells has not yet been studied. In our present study we used macrophage/neutrophil-specific gp130 knockout (gp130(ΔLys), KO) animals and analyzed its relevance in modulating Con A-induced hepatitis. Additionally, we performed in vitro studies with gp130(ΔLys)-macrophages. We demonstrate that gp130(ΔLys) animals are more susceptible to Con A-induced hepatitis. This is reflected by higher transaminases, higher lethality and more severe liver injury as shown by histological staining. Using flow cytometry analysis we further could show that increased liver injury of gp130(ΔLys) animals is associated with a stronger infiltration of CD11b/F4/80 double-positive cells compared to wild-type (gp130(flox/flox), WT) controls. To further characterize our observations we studied thioglycolate-elicited peritoneal macrophages from gp130(ΔLys) animals. Interestingly, the LPS-dependent IL-6 release in gp130(ΔLys) macrophages is significantly reduced (p<0.05) compared to WT macrophages. Additionally, IL-6 blood levels in vivo after Con A injection were significantly lower in gp130(ΔLys) animals compared to WT animals (p<0.05). In summary, our results suggest that gp130-deletion in macrophages and granulocytes leads to diminished IL-6 release from these cells, which is associated with more severe Con A-induced hepatitis.
