Proton MR spectroscopy of neurometabolites in hepatic encephalopathy during L-ornithine-L-aspartate treatment--results of a pilot study.
Hepatic encephalopathy (HE) is associated with typical changes in neurometabolites most likely being caused by an elevated systemic ammonia level. Blood ammonia is a valid over-all biomarker of HE and thus is regularly determined in clinical trials. The neurometabolites affected in HE can be assessed in vivo by proton magnetic spectroscopy. The aim of this study was to show the effect of the ammonia lowering drug L-ornithine-L-aspartate (OA) on the cerebral glutamate+glutamine/creatine (Glu+GLN/Cr) ratio. In an open clinical trial (pilot study), 15 patients with stable HE were treated with an infusion of 40 g OA over 8 h (5 g/h). Immediately before and 6-8 (mean 6.8) h after start of the infusion, spectroscopy of the parietal white matter was performed and arterial blood ammonia quantified. Glu+GLN/Cr-ratios correlated significantly with ammonia data (Spearman's correlation coefficient rs = 0.72, p < 0.001). Likewise, the OA induced changes (versus baseline before infusion) in blood ammonia level and in Glu+GLN/Cr-ratios correlated significantly rs = 0.54, p = 0.0375). Magnetic resonance (MR) spectroscopy assesses the neurometabolite variation present in HE. OA induced changes in cerebral Glu+GLN/ Cr-ratio were significantly correlated with the drug effects on arterial blood ammonia. These pilot data indicate that MR spectroscopy detects a specific biomarker of HE that may reflect the extent of the cerebral alterations associated with the disease.
Delcker
A
A
Clinical Research Department, Merz Pharmaceuticals, GmbH Frankfurt/Main, Germany. andreas.delcker@merz.de
Turowski
B
B
Mihm
U
U
Raab
P
P
Rusch
O
O
Pilatus
U
U
Zeuzem
S
S
Zanella
F E
FE
D000368:Aged; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003401:Creatine / Q000378:metabolism; D004151:Dipeptides / Q000627:therapeutic use*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D016896:Treatment Outcome
D004151:Dipeptides; D005973:Glutamine; D018698:Glutamic Acid; C002939:ornithylaspartate; D003401:Creatine