title: Canals of Hering loss relates to the progression of the histological stages of primary biliary cirrhosis.
abstract: OBJECTIVE
  The canals of Hering (CoH), which are the most peripherally located bile drainage pathway, are considered a niche of hepatic progenitor cells. Recently, CoH loss has been described as an early feature of primary biliary cirrhosis (PBC). We investigated the correlation between CoH loss and the histopathological variables of PBC.
  
  
  METHODS
  Liver biopsy specimens from 62 PBC patients (M:F=8:54, age=58 ± 12 years) were evaluated prior to ursodeoxycholic acid treatment. Liver biopsies of patients with normal liver (n=11), chronic viral hepatitis (n=36) and non-alcoholic fatty liver disease (n=13) were used as controls. The number of CoH per definite area of hepatic parenchyma (c to p ratio) was calculated in individual cases. We compared the c to p ratios of PBC patients with that of controls and analysed the correlations with histological variables and clinical features.
  
  
  RESULTS
  The c to p ratios in PBC patients with mild and extensive fibrosis were lower than those in controls with each degree of fibrosis. The c to p ratios were negatively correlated with stage, fibrosis, bile duct loss, orcein-positive granule deposition and hepatitis activities in PBC (p<0.01) and with alkaline phosphatase and total bilirubin levels at liver biopsies (p<0.05).
  
  
  CONCLUSIONS
  The number of CoH was low in early stages and further decreased with stage progression in PBC. CoH loss, reflecting a reduced supply of progenitor cells to the biliary tree, may be involved in the histological progression of PBC.
authors.affiliation: Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kakuda
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.affiliation: Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000032:analysis; D001653:Bile Ducts, Intrahepatic / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D001663:Bilirubin / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D013234:Stem Cells / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D013997:Time Factors; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D014580:Ursodeoxycholic Acid; D000469:Alkaline Phosphatase; D001663:Bilirubin