title: Roles of hepatic progenitor cells activation, ductular reaction proliferation and Notch signaling in morbid obesity.
abstract: OBJECTIVE
  Hepatic progenitor cells (HPCs) activation, proliferative ductular reaction (DR), replicative arrest and Notch signaling have been demonstrated in a variety of human liver diseases. The relationships are poorly understood in morbid obesity. We investigated factors responsible for the HPCs/DR, replicative arrest and Notch signaling in non-NASH and NASH groups.
  
  
  METHODS
  Cytokeratin 7 (and 19), p21, CD34, Ki67 and different Notch receptors and ligands immunohistochemical stained biopsies from morbid obese patients with non-NASH (n=10) and NASH (n=25) were studied. These results were correlated with clinicopathological variables.
  
  
  RESULTS
  NASH patients presented with abnormal liver function tests and had higher HbA1c percentage. Strong association between HPCs and DR was seen (r=0.785, p<0.000). BMI, interface activity and replicative arrest were associated with HPCs expansion and DR in NASH patients. A strong association between CD34 with HPCs and DR was found in non-NASH patients. In NASH group, Notch 3 was important in bile ductular proliferation; whereas Notch 4 was associated with sinusoidal neovessels proliferation and Kupffer cell activation.
  
  
  CONCLUSIONS
  HPCs and DR played an important role in hepatic regeneration in fatty liver disease of morbid obesity. An altered replication pathway in NASH promotes HPCs activation and DR. Notch-3 and Notch-4 were significantly different between non-NASH and NASH groups.
authors: Department of Pathology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
authors: Phui-Ly
authors: PL
authors: Liew
authors: Weu
authors: W
authors: Wang
authors: Yi-Chih
authors: YC
authors: Lee
authors: Ming-Te
authors: MT
authors: Huang
authors: Wei-Jei
authors: WJ
authors: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D001653:Bile Ducts, Intrahepatic / Q000737:chemistry* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D016022:Case-Control Studies; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D005234:Fatty Liver / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007728:Kupffer Cells / Q000737:chemistry / Q000473:pathology; D016014:Linear Models; D008099:Liver / Q000737:chemistry* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D009767:Obesity, Morbid / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D051880:Receptors, Notch / Q000032:analysis*; D015398:Signal Transduction; D013234:Stem Cells / Q000737:chemistry* / Q000473:pathology; D013624:Taiwan; D055815:Young Adult
chemical_list: D015415:Biomarkers; D051880:Receptors, Notch