title: 13C-methionine breath test detects distinct hepatic mitochondrial dysfunction in HIV-infected patients with normal serum lactate.
abstract: OBJECTIVE
  To assess mitochondrial respiratory chain dysfunction in different treatment groups of HIV-infected patients with normal serum lactate by measuring hepatic mitochondrial decarboxylation capacity by the C-methionine breath test (MeBT) and to correlate MeBT results with mitochondrial DNA (mtDNA) content in peripheral blood mononuclear cells (PBMCs).
  
  
  METHODS
  Four groups were studied: HIV-negative controls (n = 10), treatment-naive patients (n = 15), antiretroviral therapy (ART)-treated patients with asymptomatic disease (n = 15), and patients with long-term treatment and clinical evidence of lipoatrophy (n = 15). After oral administration of C-methionine, CO2 exhalation was determined by infrared spectroscopy. MtDNA content in PBMCs was assessed by real-time polymerase chain reaction quantification.
  
  
  RESULTS
  CO2 exhalation in lipoatrophic patients and therapy-naive patients was distinctly decreased when compared with that in healthy controls and asymptomatic patients (P < 0.001). The functional mitochondrial impairment in lipoatrophic patients was associated with a 47% decline in mtDNA content. MeBT results and mtDNA were significantly correlated in ART-treated patients (r = 0.77, P < 0.0001).
  
  
  CONCLUSIONS
  MeBT is a simple noninvasive method to detect mitochondrial dysfunction in HIV-infected patients that correlates with mtDNA depletion in PBMCs of ART-treated individuals. Decreased hepatic methionine metabolism in therapy-naive patients may reflect the functional relevance of viral-mediated mitochondrial toxicity.
authors.affiliation: Department of Internal Medicine, St. Josef-Hospital, University of Bochum, Bochum, Germany. mbanasch@gmx.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Banasch
authors.forename: Oliver
authors.initials: O
authors.lastname: Goetze
authors.forename: Ivo
authors.initials: I
authors.lastname: Hollborn
authors.forename: Bettina
authors.initials: B
authors.lastname: Hochdorfer
authors.forename: Kerem
authors.initials: K
authors.lastname: Bulut
authors.forename: Renate
authors.initials: R
authors.lastname: Schlottmann
authors.forename: Dirk
authors.initials: D
authors.lastname: Hagemann
authors.forename: Norbert H
authors.initials: NH
authors.lastname: Brockmeyer
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Schmidt
authors.forename: Frank
authors.initials: F
authors.lastname: Schmitz
mesh_terms: D000328:Adult; D001944:Breath Tests; D002247:Carbon Isotopes; D003430:Cross-Sectional Studies; D004272:DNA, Mitochondrial / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D008715:Methionine / Q000032:analysis*; D008930:Mitochondria, Liver / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012044:Regression Analysis
chemical_list: D002247:Carbon Isotopes; D004272:DNA, Mitochondrial; D019344:Lactic Acid; D008715:Methionine