title: Plasma bile acid concentrations in patients with human immunodeficiency virus infection receiving protease inhibitor therapy: possible implications for hepatotoxicity.
abstract: OBJECTIVE
  To evaluate whether patients with human immunodeficiency virus (HIV) infection who were receiving protease inhibitor therapy had altered bile acid concentrations compared with noninfected control subjects, and whether bile acid concentrations could predict the onset of hepatotoxicity caused by protease inhibitors.
  
  
  METHODS
  Retrospective sample analysis from a prospectively conducted clinical trial.
  
  
  METHODS
  Academic research center.
  
  
  METHODS
  Eleven adults with advanced HIV disease who were taking protease inhibitor-based antiretroviral therapy, one of whom had developed protease inhibitor-induced hepatotoxicity.
  
  
  RESULTS
  Plasma concentrations of cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), and taurocholic acid (TC) were analyzed by using a novel high-performance liquid chromatography with tandem mass spectrometry detection method. Comparisons of the relative contribution of each bile acid to the total bile acid pool were made with previously published values and with bile acid concentrations contained in two pooled plasma samples from healthy, non-HIV-infected volunteers analyzed in our laboratory. Each pooled plasma sample used for this analysis contained contributions from three non-HIV-infected volunteers. The LCA and TC concentrations in HIV-infected patients were 3-4-fold higher than those previously reported for non-HIV-infected subjects; concentrations of other bile acids were similar to those of previous reports. The relative contribution of CDCA to the total bile acid pool was 9% in HIV-infected patients compared with 30-50% in noninfected subjects. Total and individual bile acid concentrations in the HIV-infected patient who developed hepatotoxicity were similar to the bile acid concentrations from the other study patients who did not develop hepatotoxicity.
  
  
  CONCLUSIONS
  These data suggest that bile acid concentrations may be altered by HIV infection and/or protease inhibitor therapy. However, further investigations should be performed to assess whether antiretroviral-associated hepatotoxicity can be predicted by alterations in individual bile acid concentrations.
authors.affiliation: University of North Carolina at Chapel Hill, 27599-7360, USA.
authors.forename: MaryPeace
authors.initials: M
authors.lastname: McRae
authors.forename: Naser L
authors.initials: NL
authors.lastname: Rezk
authors.forename: Arlene S
authors.initials: AS
authors.lastname: Bridges
authors.forename: Amanda H
authors.initials: AH
authors.lastname: Corbett
authors.forename: Hsiao-Chuan
authors.initials: HC
authors.lastname: Tien
authors.forename: Kim L R
authors.initials: KL
authors.lastname: Brouwer
authors.forename: Angela D M
authors.initials: AD
authors.lastname: Kashuba
mesh_terms: D000328:Adult; D001647:Bile Acids and Salts / Q000097:blood*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology*; D002635:Chenodeoxycholic Acid / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D042241:Early Diagnosis; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008095:Lithocholic Acid / Q000097:blood; D008099:Liver / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry; D013656:Taurocholic Acid / Q000097:blood; D013997:Time Factors
chemical_list: D001647:Bile Acids and Salts; D017320:HIV Protease Inhibitors; D002635:Chenodeoxycholic Acid; D013656:Taurocholic Acid; D008095:Lithocholic Acid