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/kg L-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.

Figure 1

Typical phosphorus-31 magnetic resonance spectra obtained from a healthy volunteer, a patient with well compensated cirrhosis, and a patient with decompensated cirrhosis prior (Pre) to and after administration of L-alanine. Significantly elevated phosphomonoesters (PME) and reduced phosphodiesters (PDE) in both patient groups compared with controls at baseline is evident. Following administration of L-alanine, there was a significant increase in PME resonance in both healthy volunteers and patients with compensated cirrhosis which returned to baseline values after 90 minutes. Patients with decompensated cirrhosis showed increased PME at baseline which remained virtually unchanged after L-alanine. P_i, inorganic phosphate; NTP, nucleotide triphosphate.

Figure 2

Changes in (A) percentage phosphomonoester (%PME) and (B) percentage inorganic phosphate (%P_i) after infusion of L-alanine in healthy volunteers, and in patients with compensated cirrhosis and decompensated cirrhosis.

Figure 3

Plasma insulin, glucagon, glucose, and alanine concentrations in healthy volunteers, and in patients with compensated and decompensated cirrhosis prior to and after administration of L-alanine.

Figure 4

Plasma lactate, plasma urea, and capillary ammonia concentrations in healthy volunteers and in patients with compensated and decompensated cirrhosis prior to and after administration of L-alanine.