Brain Imaging in Patients With Chronic Liver Disease and Functional Impairment.
Condition: Cirrhosis; Hepatic Encephalopathy
MeSH terms: Hepatic Encephalopathy; Brain Diseases; Fibrosis
Study type: Interventional

Summary: 
      Hepatic encephalopathy (HE) is a frequent complication of chronic liver disease (cirrhosis)
      and involves a wide spectrum of problems from mild impairment of reaction times in driving
      and operating machinery through to disturbances in mood, behaviour and conscious levels.

      Magnetic resonance imaging (MRI) is a method of obtaining pictures of the inside of the body.
      Patients with liver disease have previously been studied with MRI which has highlighted
      changes in the brain. This research aims to highlight some of the differences in the way that
      the brain functions in patients with liver disease. Using our new, more powerful MRI scanner,
      with more sophisticated techniques we hope that the novel combination of MRI techniques can
      objectively detect the presence of , and monitor HE.

      Study hypothesis: Hepatic encephalopathy (HE) is a reversible, metabolic disturbance of the
      brain, associated with low grade brain swelling and disturbances of the chemical balance
      within the brain, resulting in functional impairment, the presence of which MR imaging can
      detect with sufficient sensitivity to monitor the changes that may occur over time in
      response to treatment.
    

Detailed description: 
      Hepatic encephalopathy (HE) is a common neuropsychiatric abnormality, complicating the course
      of liver disease patients. In the UK, cirrhosis accounts for 4000 deaths per year, and
      500,000 people are thought to be infected with chronic hepatitis C, of which up to 20% will
      develop cirrhosis over 20 years. The condition has been difficult to monitor objectively.

      Despite the fact that the syndrome was probably first recognised two thousand years ago, the
      exact pathogenesis still remains unclear. It is thought to represent a reversible disturbance
      in brain chemistry and consequent brain swelling, in response to blood containing unfiltered
      gut-derived toxins entering the cerebral circulation. There is no recognised 'gold standard'
      test to diagnose and monitor this important, disabling condition. I have developed a novel
      combination of magnetic resonance imaging (MRI) sequences at 3 Tesla to study the effects of
      hepatic encephalopathy on the brain in patients with cirrhosis.

      We propose to investigate alterations in brain size, function and chemistry before, and then
      at intervals after 4 weeks anti-encephalopathy treatment with L-ornithine L-aspartate. This
      will enable the assessment of both the baseline brain alterations of the cohort and the
      brain's response to therapy and correlation with their clinical response. As such this
      longitudinal study would allow us to define the sensitivity of the MR techniques.

      Each of 50 patients will have blood tests, a 1 hour MRI brain scan and psychometric testing.
      The psychometric testing will be performed with both a computer-based battery and
      conventional paer-based tests. They will then be given L-ornithine L-aspartate (LOLA) to take
      orally for 4 weeks and have repeat blood tests, MRI and psychometric tests.

      We will then determine if there is a correlation between the MR data and the results of the
      psychometric testing.
    

Intervention name(s): l-ornithine l-aspartate
Intervention type(s): Drug
Intervention MeSH terms: N-Methylaspartate
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: magnetic resonance imaging; magnetic resonance spectroscopy; functional magnetic resonance imaging; cirrhosis; hepatic encephalopathy; l-ornithine l-aspartate