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Results
Fifty-five patients [30 male (54.5%), 25 female (45.5%)] with a mean age of 52 years (range: 19–68 years) were included into the study (Table 1). The underlying liver disease was alcohol related in 13 (23.6%), Hepatitis C virus (HCV) infection in 18 (32.7%), Hepatitis B virus (HBV) infection in 6 (10.9%), primary sclerosing cholangitis (PSC) in 7 (12.7%), primary biliary cirrhosis (PBC) in 3 (5.5%), autoimmune hepatitis in 2 (3.6%) and cryptogenic in 6 (10.9%) cases. 41 patients (74.5%) had no or less than 5 lesions (group 1; 27 of these (49.1%) showed no T2-weighted focal lesions in the white matter). 8 patients (14.5%) showed more than 5 but less than 15 (group 2) and 6 patients (10.9%) had 15 or more focal white matter lesions (group 3) (Table 1; Fig. 1). Group one had a median number of 0 lesions, group two showed a median number of 7 lesions, while the median number of lesions in group 3 was 18 (P < 0.001).
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Figure 1.
MRI of a patient from group three which comprised 19 white matter lesions with a diameter above 3 mm. Of note besides these lacunar-like lesions (white arrows) the example also shows extended Virchow–Robin's spaces (black arrow).
The three patient groups differed significantly with regard to age (anova:P < 0.05). In pair-wise comparisons a significant difference was shown between group 1 and 2 (P < 0.05). The mean age of patients with ≥15 white matter lesions (group 3) was similar to that of group 2, but here a significant difference to group 1 could not be shown because of the smaller number of patients. Regression analysis showed a significant positive correlation between age and the number of white matter lesions (r = 0.544, P < 0.001). The time from diagnosis of cirrhosis until examination in this study ranged between 5 and 216 months (median: 55 months). There was no significant difference between the three patient groups and no correlation between the time from diagnosis of cirrhosis and number of white matter lesions.
Overall the patients had a MELD score of 13.1 (SD 4.16, max. 25, min. 7). There was no significant difference between the three patient groups concerning the MELD score and no significant correlation between MELD score and number of white matter lesions.
The three patient groups showed no significant difference regarding the underlying liver disease (Table 2). There was also no significant difference between the three groups with regard to the presence of the vascular risk factors hypertension, diabetes and renal insufficiency (Table 1). The remarkable percentage of patients with focal lesions in the PBC group cannot be evaluated since in all only 3 PBC patients were included into this study.
Twenty-eight patients (50.9%) had a history of hepatic encephalopathy. At the time point of the clinical examination 45 (81.8%) patients showed no signs of overt HE, 7 (12.7%) patients had grade 1 HE and 3 patients grade 2 (5.5%) HE. Minimal HE was diagnosed in 8 patients using the PHES (19%). Three patients without clinical signs of HE could not perform the test because of deficits in German language. Thirty-three (60%) patients were treated with lactulose and/or L-ornithine-L-aspartate (LOLA) to prevent HE.
Owing to limited availability of the MRI machine, MRI could be performed within 24 h after the first examination including psychometric testing in only 25 patients, 9 underwent MRI within 4 weeks, the remaining 21 in median within 3 months after psychometric testing (min: 2; max: 13). The clinical grade of HE was re-evaluated in these patients before the MRI examination. Therefore, all patients were included into the analysis except for the correlation analysis between MRI findings and the results of the psychometric tests. These were done for those studied within 24 h, exclusively. Twenty-three of the 25 patients accomplished the PSE-Syndrome-Test. One of the remaining two patients was blind, the other could not use his right hand. Sixteen patients belonged to group 1, 4 to group 2 and three to group 3. The PHES ranged between +3 and −10 in group 1, 0 and −13 in group 2 and −4 and −11 in group 3 (Table 3). 21 of these patients completed the RBANS test: 14 in group 1, 4 in group 2 and three in group 3. Like for the PHES, both, the subscores as well as the total score decreased from group 1 to group 2 and group 3. The difference, however, was not significant, probably because of the small number of cases in groups 2 and 3.
Spearman correlation showed a significant negative correlation between the PHES and the number of white matter lesions (r = −0.490, P = 0.018) as well as the RBANS total score and the number of white matter lesions (r = −0.487, P = 0.025). A significant correlation was also observed between the number of white matter lesions and the following subscores of the RBANS: visuo-spatial/constructional ability (r = − 0.511, P = 0.018; attention (r = −0.457, P = 0.037); and delayed memory (r = −0.594, P = 0.004).
Spearman correlation between the clinical grade of HE (including grades 0, HE grade 1 and 2) and the number of white matter lesions showed a significant relationship (r = 0.294, P = 0.029; n = 55). In the subgroup of patients who underwent psychometry within 24 h of MRI where mHE was also considered, the relationship between the grade of HE and the number of white matter lesions became even more visible: the correlation coefficient was 0.484, and the P = 0.014. Of note, there was no significant correlation between age and the number of white matter lesions in this subgroup (P = 0.104).
A multiple regression analysis for the whole patient group including the number of white matter lesions as dependent and age, clinical grade of HE, history of HE, hypertension, renal insufficiency and diabetes as independent variables using a stepwise exclusion model showed a significant interdependency between the number of white matter lesions and the grade of HE, exclusively (P < 0.001) (Fig. 2). There was only a tendency of relationship between age and white matter lesions (P = 0.092).
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Figure 2.
Patients with 8 and more white matter lesions all had a history of hepatic encephalopathy.
Of note all patients with more than 8 white matter hyperintensities had experienced at least one HE episode (Fig. 2).
14 patients died between 1 and 37 months (mean 12.9 month) after inclusion into this study. Thus, the mortality rate was 25.5%. 7 (12.7%) patients died while on the waiting list for liver transplantation and 7 (12.7%) patients died after liver transplantation. There was no significant difference in the number of white matter lesions in deceased and not deceased patients.
Eleven patients underwent a follow-up MRI about 1 year after LTx. The number of white matter lesions remained stable after liver transplantation (P = 0.16).
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