Minimal hepatic encephalopathy in children with chronic liver disease: Prevalence, pathogenesis and magnetic resonance-based diagnosis.
Data on minimal hepatic encephalopathy (MHE) in children is scarce. We aimed to study MHE in children with chronic liver disease (CLD) and to validate non-invasive objective tests which can assist in its diagnosis.



We evaluated 67 children with CLD (38 boys; age 13 [7-18] years) and 37 healthy children to determine the prevalence of MHE. We also assessed the correlation of MHE with changes in brain metabolites by magnetic resonance spectroscopy (1HMRS), diffusion tensor imaging (DTI) derived metrics, blood ammonia and inflammatory cytokines (interleukin-6 [IL6], tumor necrosis factor alpha [TNF-α]). In addition, the accuracy of MR-based investigations for diagnosis of MHE in comparison to neuropsychological tests was analysed.



Thirty-four (50.7%) children with CLD had MHE on neuropsychological tests. MHE patients had higher BA (30.5 [6-74] vs. 14 [6-66]μmol/L; p=0.02), IL-6 (8.3 [4.7-28.7] vs. 7.6 [4.7-20.7]pg/ml; p=0.4) and TNF-α (17.8 [7.8-65.5] vs. 12.8 [7.5-35]pg/ml; p=0.06) than No-MHE.1HMRS showed higher glutamine (2.6 [2.1-3.3] vs. 2.4 [2.0-3.1]; p=0.02), and lower choline (0.20 [0.14-0.25] vs. 0.22 [0.17-0.28]; p=0.1) and myo-inositol (0.25 [0.14-0.41] vs. 0.29 [0.21-0.66]; p=0.2) in MHE patients than those without MHE. Mean diffusivity (MD) on DTI was significantly higher in 6/11 brain areas in patients with MHE vs. no MHE. Brain glutamine had a significant positive correlation with blood ammonia, IL-6, TNF-α and MD of various brain regions. Neuropsychological tests showed a negative correlation with blood ammonia, IL6, TNF-α, glutamine and MD. Frontal white matter MD had a sensitivity and specificity of 73.5% and 100% for diagnosing MHE.



In children with CLD, 50% have MHE. There is a significant positive correlation between markers of hyperammonemia, inflammation and brain edema and these correlate negatively with neuropsychological tests. MD on DTI is a reliable tool for diagnosing MHE.



Fifty percent of children with chronic liver disease develop minimal hepatic encephalopathy (MHE) and perform poorly on neuropsychological testing. These children have raised blood ammonia, inflammatory cytokines and mild cerebral edema on diffusion tensor imaging as compared to children without MHE. The higher the ammonia, inflammatory cytokines and cerebral edema levels the poorer the performance on neuropsychological assessment. The estimation of mean diffusivity on diffusion tensor imaging is an objective and reliable method for diagnosing MHE.
Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. Electronic address: avanianshu@yahoo.com.
Anshu
A
Srivastava
Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Saurabh
S
Chaturvedi
Department of Radiodiagnosis, Fortis Hospital, Gurgaon, India.
Rakesh Kumar
RK
Gupta
Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Rohan
R
Malik
Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Amrita
A
Mathias
Department of NMR and MRI Facility, All India Institute of Medical Sciences, Delhi, India.
Naranamangalam R
NR
Jagannathan
Department of Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Sunil
S
Jain
Department of Biostatistics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Chandra Mani
CM
Pandey
Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Surender Kumar
SK
Yachha
Department of Mathematics and Statistics, Indian Institute of Technology, Kanpur, India.
Ram Kishor Singh
RKS
Rathore
D000293:Adolescent; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D056324:Diffusion Tensor Imaging; D005260:Female; D006501:Hepatic Encephalopathy / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D007194:India / Q000453:epidemiology; D008107:Liver Diseases / Q000150:complications*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009483:Neuropsychological Tests; D015995:Prevalence
D016207:Cytokines
(1)H Magnetic resonance spectroscopy; Children; Chronic liver disease; Diffusion tensor imaging; Hyperammonemia; Minimal hepatic encephalopathy; Neuropsychological tests