Detektion und Therapieverlaufskontrolle der subklinischen und manifesten hepatischen Enzephalopathie nach Behandlung mittels L-Ornithin-L-Aspartat durch Protonen-Magnetresonanzspektroskopie (¹H-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.