Cerebral magnetic resonance imaging reveals marked abnormalities of brain tissue density in patients with cirrhosis without overt hepatic encephalopathy

Background & Aims

We applied advanced magnetic resonance imaging and Voxed based Morphometry analysis to assess brain tissue density in patients with cirrhosis.

Methods

Forty eight patients with cirrhosis without overt hepatic encephalopathy (17 Child A, 13 Child B, and 18 Child C) and 51 healthy subjects were matched for age and sex. Seventeen patients had history of overt hepatic encephalopathy, eight of them had minimal hepatic encephalopathy at inclusion, 10 other patients had minimal hepatic encephalopathy at inclusion but without history of previous overt hepatic encephalopathy, and 21 patients had none of these features.

Results

Patients with cirrhosis presented decreased brain density in many areas of the grey and white matter. The extension and size of the affected areas were greater in patients with alcoholic cirrhosis than in those with post-hepatitic cirrhosis and correlated directly with the degree of liver failure and cerebral dysfunction (as estimated by neuropsychological tests and the antecedent of overt hepatic encephalopathy). Twelve additional patients with cirrhosis who underwent liver transplantation were explored after a median time of 11 months (7–50 months) after liver transplant. At the time of liver transplantation, three patients belonged to class A of the Child-Pugh classification, five to class B and four to class C. Compared to healthy subjects, liver transplant patients showed areas of reduced brain density in both grey and white matter.

Conclusions

These results indicate that loss of brain tissue density is common in cirrhosis, progresses during the course of the disease, is greater in patients with history of hepatic encephalopathy, and persists after liver transplantation. The significance, physiopathology, and clinical relevance of this abnormality cannot be ascertained from the current study.

Introduction

Hepatic encephalopathy is a cerebral disorder of patients with liver failure and/or porto-systemic shunting caused by ammonia and other endogenous substances that escape from hepatic metabolism [1]. The spectrum of the syndrome ranges from minimal hepatic encephalopathy to deep coma. Since hepatic encephalopathy reverses in most patients after appropriate treatment, it is considered a functional disorder [2]. The methodology used to explore cerebral function in cirrhosis includes: the EEG and the mean dominant frequency, neuropsychological tests exploring attention and cognitive functions, and the critical flicker frequency and other recently introduced computerized tests that estimate the reactive ability of the patients to a visual stimulus [3], [4], [5], [6]. Most of these tests have been developed to diagnose minimal hepatic encephalopathy.

Magnetic resonance imaging is widely used for research and diagnosis of cerebral diseases. Voxel-based Morphometry, which measures brain tissue density (concentration), has been proved of great interest in the assessment of regional areas of atrophy in neurodegenerative cerebral diseases such as Alzheimer‘s Disease, Huntington’s Chorea, and Multiple Sclerosis [7], [8], [9], [10], [11]. Regional areas of density loss diagnosed by Voxel-Based Morphometry in Alzheimer Disease correlate with areas of atrophy on histopathology [12].

The current article reports the first study using Voxel-based Morphometry in a large series of patients with cirrhosis of different aetiologies, with and without previous history of hepatic encephalopathy but without overt hepatic encephalopathy at the time of the investigation. The aim of the study was to assess brain tissue density in patients with cirrhosis and its relationship with the severity of the disease and history of hepatic encephalopathy.