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We hypothesized that lack of the high-energy phosphates during liver storage may potentially cause persistent injury to the vascular endothelium. Biopsies were obtained from livers obtained from beating heart human donors, stored either in the standard storage solution, that is, University of Wisconsin solution (UWS) or Celsior, and examined for various markers related to progressive endothelial injury. The expression of P2Y1 receptor, the major signal transduction machinery for adenosine triphosphate/adenosine diphosphate, decreased in hepatic vascular endothelial cells over time. Despite unaltered endothelial nitric oxide synthase (eNOS) levels, serine1177- phosphorylated eNOS, the active form of eNOS, progressively decreased with time. The production of nitric oxide enzyme decreased with time when liver tissues were examined in vitro. This also coincided with decreased interaction of eNOS with actin nucleating proteins like myristoylated alanine-rich C kinase substrate and Rac1, which plays a role in modulating the cytoskeleton and helps position eNOS in a favorable cytosolic position for active enzymatic activity. Conversely, the interaction of eNOS with caveolin1 was significantly increased 6 H after ex vivo storage. Finally, we demonstrated by targeted contrast-enhanced ultrasound that membrane-bound vascular cell adhesion molecule-1 in the hepatic vascular endothelial cell increased after 6 H of ex vivo storage. Overall, the results of this study provide evidence of a progressive hepatic vascular endothelial injury during the ex vivo storage. This may be a causative factor for ischemic cholangiopathy and delayed graft function post liver transplantation. [ABSTRACT FROM AUTHOR]

Background and Aim: The purpose of this study was to assess the clinical value and potential impact of contrast-enhanced ultrasound (CEUS) in the characterization of undetermined focal liver lesions (FLLs) in patients with fatty liver. Methods: Fifty-two patients (34 men, 18 women) with fatty liver with 67 FLLs (size range, 1–8.6 cm; mean, 4.1 ± 3.1 cm) undetermined at baseline ultrasound (US) underwent contrast-enhanced US. CEUS examinations were analyzed by two experienced sonologists blinded to the final diagnosis. Readers evaluated by consensus the baseline echogenicity, the dynamic enhancement pattern in comparison with peripheral liver parenchyma. The final diagnosis was based on consensus interpreting of all examinations by another two expert observers with access to histological data. The characterization accuracy, sensitivity, and specificity of CEUS in characterizing the lesion as benign or malignant, and as the correct pathologic type, were analyzed. Results: After CEUS, two hemangiomas, three inflammatory pseudotumors, and one hepatocellular carcinoma were misdiagnosed. The overall characterization accuracy, sensitivity and specificity of CEUS were 91% (61/67), 91.7% (11/12), and 90.9% (50/55), respectively. Forty-three benign lesions were diagnosed as the correct pathologic type. The portal venous phase and late phase were important in the characterization of the lesions. The characterization accuracy had no relationship with the size of FLLs. Conclusion: CEUS can improve the characterization of undetermined FLLs arising from fatty liver. [ABSTRACT FROM AUTHOR]