H epatic fibrosis associated with inflammatory cell infiltration is a prominent feature of persistent infection by hepatitis B virus (HBV) and hepatitis C virus (HCV). The hepatic stellate cell (HSC) has assumed a central role in this response after its activation by inflammatory cytokines and mediators. [1][2][3][4][5] The cellmediated immune response after viral hepatitis reflects the activity of CD4ϩ helper T and CD8ϩ cytotoxic T
Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is accompanied by inflammation and fibrosis eventually leading to cirrhosis. The chemokine CXCL12 is involved in chronic inflammatory conditions. The role of the CXCL12/CXCR4 pathway in HCV-and HBV-associated liver inflammation and fibrosis was therefore studied. The levels and tissue localization of CXCL12 in liver and plasma of HCV and HBV patients were tested using immunohistochemistry and ELISA. The expression and function of CXCR4 on liver-infiltrating lymphocytes (LIL) were tested by FACS and transwell migration assays. We found that CXCL12 is expressed by bile duct epithelial cells in normal liver tissue. Bile duct proliferation and liver fibrosis in chronic HCV and HBV infection result in the anatomical re-distribution of CXCL12 in the liver. Moreover, CXCL12 is up-regulated in the endothelium of neo-bloodvessels formed in active inflammatory foci and is significantly elevated, compared with controls, in the plasma of patients with advanced liver fibrosis. Complementing these observations were others indicating that over 50% of LIL express CXCR4 and, in response to CXCL12, migrated and adhered to fibronectin. These observations suggest an important role for the CXCL12/CXCR4 pathway in recruitment and retention of immune cells in the liver during chronic HCV and HBV infection.
It is possible to extend significantly the life expectancy of uveal melanoma patients who develop isolated hepatic metastases by complete resection of the lesions.
miRNA quantification for differential diagnosis of thyroid neoplasms within aspiration biopsy samples is feasible and may improve the accuracy of FNAB cytology.
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