title: Apoptotic and anti-apoptotic seromarkers for assessment of disease severity of non-alcoholic steatohepatitis.
abstract: OBJECTIVE
  This study aimed to find out non-invasive markers for the assessment of severity of non-alcoholic steatohepatitis (NASH) in an attempt to decrease the need for liver biopsy. It also aimed to evaluate the key role of apoptosis in the pathogenesis of the disease and the suggested role of anti-apoptotic factors in therapeutic modalities and disease prognosis.
  
  
  METHODS
  The serum levels of soluble Fas (s. Fas), s. Fas ligand, cytokeratin 18 (CK-18) fragment and Bcl-2 were measured in 80 patients and 15 non-hepatic subjects as control. The patients were divided based on histological examination of liver biopsy into three groups. Group I included 40 patients with NASH, group II had 40 patients with non-alcoholic fatty liver disease (NAFLD) non-NASH and group III had 15 non-hepatic subjects as control. Apoptosis of hepatocytes was assessed by morphological examination using a light microscope and expressed as number per square millimetre.
  
  
  RESULTS
  There was a significant increase in the serum levels of s. Fas, s. Fas ligand and CK-18 fragments in the NASH group. The anti-apoptotic protein Bcl-2 showed significantly low levels in NASH patients. Apoptosis of hepatocytes was significantly higher in the NASH group. The degree of apoptosis was inversely correlated with the level of Bcl-2. A significant correlation between both s. Fas and CK-18 fragment with liver histology with regard to lobular inflammation and ballooning was found.
  
  
  CONCLUSIONS
  Increased serum levels of s. Fas and CK-18 fragment in the NASH group and its correlation with the severity of disease suggested the key role of apoptosis in NASH pathogenesis which can be used for the assessment of the severity of NASH. A high level of anti-apoptotic Bcl-2 in NAFLD suggests its protective role in disease progress.
authors.affiliation: Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt.
authors.forename: Hanan
authors.initials: H
authors.lastname: El Bassat
authors.affiliation: Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt. Electronic address: dhz646@hotmail.com.
authors.forename: Dina H
authors.initials: DH
authors.lastname: Ziada
authors.affiliation: Department of Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt.
authors.forename: Eiman A
authors.initials: EA
authors.lastname: Hasby
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt.
authors.forename: Hala
authors.initials: H
authors.lastname: Nagy
authors.affiliation: Department of General Surgery, Faculty of Medicine, Tanta University, Tanta, Egypt.
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Abo Ryia
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D053222:Fas Ligand Protein / Q000097:blood*; D005234:Fatty Liver / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D053538:Keratin-18 / Q000097:blood*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000097:blood*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D053222:Fas Ligand Protein; D053538:Keratin-18; D019253:Proto-Oncogene Proteins c-bcl-2; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Anti-apoptotic protein Bcl-2; Apoptosis; CK-18 Fragments; Non-alcoholic steatohepatitis (NASH); s. Fas; s. Fas ligand