title: Changes in classic and alternative pathways of bile acid synthesis in chronic liver disease.
abstract: BACKGROUND
  Cholesterol elimination occurs through bile acid synthesis that starts within the liver from 7alpha-hydroxylation or in extrahepatic tissues from 27-hydroxylation. This study was aimed at investigating in vivo these two pathways in patients with chronic liver disease.
  
  
  METHODS
  Serum concentrations of 7alpha- and 27-hydroxycholesterol were measured in 54 patients (29 with primary biliary cirrhosis and 25 with chronic hepatitis C) and 18 controls. The rate of oxysterol plasma appearance was calculated after intravenous infusions of deuterated 7alpha- and 27-hydroxycholesterol in patients (n=8) and control subjects (n=8) who gave consent. The expression of sterol 27-hydroxylase was evaluated in macrophages isolated from 20 subjects.
  
  
  RESULTS
  In patients with liver disease, the rate of plasma appearance of 7alpha-hydroxycholesterol was significantly reduced (1.44+/-0.96 vs. 2.75+/-1.43 mg/hour, p=0.03), the degree of reduction being related with the severity of the disease (p=0.01) whereas that of 27-hydroxycholesterol was unaffected. The rate of plasma appearance of 27-hydroxycholesterol was significantly related to its serum concentrations (r=0.54, p=0.03) and to its release from cultured macrophages ( r=0.85, p=0.03).
  
  
  CONCLUSIONS
  In liver disease 7alpha-hydroxylation of cholesterol seems to be impaired while 27-hydroxylation is unaffected. Serum concentrations of 27-hydroxycholesterol are useful to obtain information on the activity of this alternative pathway.
authors.affiliation: Department of Medicine, Surgery and Dentistry, School of Medicine San Paolo, Italy. andrea.crosignani@libero.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Crosignani
authors.forename: Marina
authors.initials: M
authors.lastname: Del Puppo
authors.forename: Matteo
authors.initials: M
authors.lastname: Longo
authors.forename: Emma
authors.initials: E
authors.lastname: De Fabiani
authors.forename: Donatella
authors.initials: D
authors.lastname: Caruso
authors.forename: Massimo
authors.initials: M
authors.lastname: Zuin
authors.forename: Mauro
authors.initials: M
authors.lastname: Podda
authors.forename: Norman B
authors.initials: NB
authors.lastname: Javitt
authors.forename: Marzia Galli
authors.initials: MG
authors.lastname: Kienle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001647:Bile Acids and Salts / Q000096:biosynthesis* / Q000378:metabolism; D053898:Biosynthetic Pathways / Q000502:physiology; D016022:Case-Control Studies; D002478:Cells, Cultured; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics / Q000378:metabolism; D005260:Female; D006521:Hepatitis, Chronic / Q000503:physiopathology*; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood / Q000378:metabolism*; D006900:Hydroxylation; D008105:Liver Cirrhosis, Biliary / Q000503:physiopathology*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D001647:Bile Acids and Salts; D006888:Hydroxycholesterols; C011724:cholest-5-en-3 beta,7 alpha-diol; C076996:27-hydroxycholesterol; D053493:Cholestanetriol 26-Monooxygenase