title: [Detection of subclinical and overt hepatic encephalopathy and treatment control after L-ornithine-L-aspartate medication by magnetic resonance spectroscopy ((1)H-MRS)].
abstract: Hepatic encephalopathy (HE) is a common problem in liver cirrhosis and is associated with typical changes of cerebral metabolite pattern observed by proton magnetic resonance spectroscopy (MRS). In HE, a reduction of the cerebral myo-inositol (mI) and choline (Cho) and an increase of glutamine/glutamate (Glx) can typically be detected with this method. In the present study MRS was used to assess prospectively specific parameters of cerebral metabolism before and after 6 days of treatment with a low-protein diet and with L-ornithine-L-aspartate (LOLA). 6 patients with liver cirrhosis were included in this pilot study. According to standardized neuropsychological tests overt HE or subclinical HE was detected in all patients. All patients received a low-protein diet (< 60 g/d) and were treated additionally with LOLA (20 g QD i. v.). MRS examinations were done before and after 6 days of treatment and the results were compared with those of healthy volunteers. Before treatment mI/Cr ratios in the grey matter were reduced significantly in cirrhotic patients as compared to healthy volunteers (0.30 +/- 0.22 vs. 0.68 +/- 0.11; P = 0.028). In addition, patients showed a (non-significant) reduction of the Cho/Cr-ratio (0.19 +/- 0.03 vs. 0.25 +/- 0.02; P = 0.17) and an elevated Glx/Cr-ratio (1.84 +/- 0.63 vs. 1.29 +/- 0.31; P = 0.05). After 6 days of treatment a significant increase of the Cho/Cr ratio (0.23 +/- 0.03 vs. 0.19 +/- 0.03; P = 0.028) was detectable and 5 of the 6 patients showed a (not significant) decrease of the elevated Glx/Cr ratios. After cessation of treatment an improvement in neuropsychological tests as shown by number-connection testing (P = 0.046) as well as a decrease of elevated pre-treatment ammonia blood levels were noted. These findings, however, did not correlate with the Child-Pugh classification or evidence of clinical/subclinical HE. Using (1)H-MRS it is possible to observe a specific pattern of cerebral metabolites in patients with overt and subclinical HE. In this pilot study a fast change of cerebral metabolite pattern after specific therapy of HE with LOLA was detected. Therefore, future studies with larger patient groups are needed to establish (1)H-MRS as an objective method for detection and treatment control in overt and subclinical HE, especially when compared to commonly used parameters such as ammonia levels or standardized neuropsychological tests.
authors.affiliation: Abteilung Gastroenterologie, Hepatologie und Infektiologie, Medizinische Klinik, Universität Tübingen. holger.hass@med.uni-tuebingen.de
authors.forename: H G
authors.initials: HG
authors.lastname: Hass
authors.forename: T
authors.initials: T
authors.lastname: Nägele
authors.forename: U
authors.initials: U
authors.lastname: Seeger
authors.forename: F
authors.initials: F
authors.lastname: Hösl
authors.forename: M
authors.initials: M
authors.lastname: Gregor
authors.forename: S
authors.initials: S
authors.lastname: Kaiser
mesh_terms: D000328:Adult; D000641:Ammonia / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002794:Choline / Q000032:analysis; D003131:Combined Modality Therapy; D003404:Creatinine / Q000032:analysis; D018753:Diet, Protein-Restricted; D004151:Dipeptides / Q000627:therapeutic use*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D018698:Glutamic Acid / Q000032:analysis; D005973:Glutamine / Q000032:analysis; D006501:Hepatic Encephalopathy / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D007294:Inositol / Q000378:metabolism; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010865:Pilot Projects; D011446:Prospective Studies; D012016:Reference Values; D013223:Statistics as Topic
chemical_list: D004151:Dipeptides; D005973:Glutamine; D018698:Glutamic Acid; D007294:Inositol; D000641:Ammonia; D003404:Creatinine; C002939:ornithylaspartate; D002794:Choline