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Evidence for altered hepatic gluconeogenesis in patients with cirrhosis using in vivo 31-phosphorus magnetic resonance spectroscopy

Abstract

BACKGROUND AND AIMS Alterations in gluconeogenesis in the diseased liver can be assessed non-invasively using magnetic resonance spectroscopy by measuring changes in phosphomonoester resonance which contains information regarding several metabolites, including the phosphorylated intermediates of the gluconeogenic pathway.

METHODS 31P magnetic resonance spectroscopy was used to determine changes in phosphomonoesters following bolus infusions of 2.8 mmol/kgl-alanine in five patients with functionally compensated cirrhosis and in five patients with functionally decompensated cirrhosis.

RESULTS Compared with six healthy volunteers, baseline phosphomonoester values were elevated by 35% (p<0.05) in the compensated cirrhosis group and by 57% (p<0.01) in the decompensated cirrhosis group. Following alanine infusion, phosphomonoesters in healthy volunteers increased by 46% from baseline values (p<0.01), in patients with compensated cirrhosis by 27% (p<0.02) but those with decompensated cirrhosis showed no increase from baseline. There was a reduction in the percentage of inorganic phosphate signal in all subjects.

CONCLUSIONS By analysing changes in phosphomonoester and inorganic phosphate resonances it is possible to discern clear metabolic differences between healthy volunteers and patients with cirrhosis of varying severity using magnetic resonance spectroscopy. Those patients with functionally decompensated cirrhosis have higher percentage baseline phosphomonoester values but the absence of phosphomonoester elevation following l-alanine infusion suggests that they are unable to mount a significant metabolic response with a progluconeogenic stimulus.

  • gluconeogenesis
  • cirrhosis
  • alanine
  • ammonia
  • glucagon
  • Abbreviations used in this paper

    AMP
    adenosine monophosphate
    AUC
    area under the curve
    BLAST
    baseline artefact subtraction technique
    G6P
    glucose-6-phosphate
    MRS
    magnetic resonance spectroscopy
    NTP
    nucleotide triphosphate
    PBC
    primary biliary cirrhosis
    PC
    phosphocholine
    PE
    phosphoethanolamine
    Pi
    inorganic phosphate
    PDE
    phosphodiesters
    PME
    phosphomonoesters
    2D-CSI
    two dimensional chemical shift imaging
    3PG
    3-phosphoglycerate
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  • Abbreviations used in this paper

    AMP
    adenosine monophosphate
    AUC
    area under the curve
    BLAST
    baseline artefact subtraction technique
    G6P
    glucose-6-phosphate
    MRS
    magnetic resonance spectroscopy
    NTP
    nucleotide triphosphate
    PBC
    primary biliary cirrhosis
    PC
    phosphocholine
    PE
    phosphoethanolamine
    Pi
    inorganic phosphate
    PDE
    phosphodiesters
    PME
    phosphomonoesters
    2D-CSI
    two dimensional chemical shift imaging
    3PG
    3-phosphoglycerate
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