title: Emerging role of adipokine apelin in hepatic remodelling and initiation of carcinogensis in chronic hepatitis C patients.
abstract: BACKGROUND
  Although accumulating data has implicated a role for the Apelinergic system in cirrhosis, the role of Apelin during different stages of fibrogenesis has not been clarified, whereas no studies have been conducted on its expression in human hepatocellular carcinoma (HCC). This study aimed to elucidate its role in hepatic remodelling and carcinogenesis.
  
  
  METHODS
  Immunolocalization of Apelin was compared during different stages of HCV-induced liver disease (n=123).
  
  
  RESULTS
  Apelin level in hepatic stellate cells (HSC), portal fibroblast and endothelial cells was significantly elevated in F3 stage .In cirrhosis, the expression was markedly striking and extended as linear staining in the cirrhotic septa and proliferated capillaries. In liver cirrhosis with high grade dysplastic nodule (HGDN) group and liver cirrhosis with HCC group, Apelin was constantly expressed in the hepatocytes with the exemption of non-parenchymatous cells. Apelin gradually increased in HGDN, HCC grade-I and HCC grade II (P<0.0001). In contrast, Apelin gradually decreased in the cirrhosis adjacent to HGDN, HCC grade-I and HCC grade II (P<0.0001). The gradual incline in Apelin expression in dysplastic and malignant cells was paralleled by a decline in their adjacent cirrhotic liver (P=0.013).
  
  
  CONCLUSIONS
  In HCV chronic hepatitis, Apelin seems to manipulate the differentiation of HSC ending in hepatic remodelling. The uptake of Apelin from the stromal components by the epithelial cells may initiate the transformation of adjacent epithelial cells and supports the evolution and progression of dysplastic nodules and hepatocellular carcinoma. These findings could have both prognostic and therapeutic applications.
authors: Department of Pathology, Faculty of Medicine, Ain Shams University Cairo, Egypt.
authors: Rola M
authors: RM
authors: Farid
authors: Department of Pathology, Faculty of Medicine, Ain Shams University Cairo, Egypt.
authors: Riham M
authors: RM
authors: Abu-Zeid
authors: Department of Pathology, Faculty of Medicine, Ain Shams University Cairo, Egypt.
authors: Ahmed
authors: A
authors: El-Tawil
mesh_terms: D000328:Adult; D000368:Aged; D000073861:Apelin; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002472:Cell Transformation, Viral; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism / Q000821:virology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000821:virology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction
chemical_list: C115436:APLN protein, human; D000073861:Apelin; D036341:Intercellular Signaling Peptides and Proteins
keywords: Apelin; HCV; cirrhosis; hepatocellular carcinoma; high grade dysplasia