Cirrhosis & Consequences

We have focus on improving the diagnostic and prognotic tools that have utility to pateints, clinicians, pharma and the healthcare system. The studies below stratify cirrhosis using a combination of simple tests, fibrosi markers and imaging tests including novel MRI protocols.

1) Quantitative Magnetic Resonance Imaging (MRI) Techniques in the Evaluation and Estimation of Portal Hypertension (MRQuee) 

Death from chronic liver disease has doubled in the UK over the last decade. This is largely due to the rise in liver disease from excess alcohol consumption, obesity related fatty liver disease and hepatitis B & C infections. The current ‘liver tests’ only identify liver injury when the damage is at an advanced stage. They neither estimate the degree of injury accurately nor help judge prognosis. The complications from chronic liver disease result mainly from raised pressures within the liver. We currently measure this pressure by passing a long catheter through the jugular vein in the neck into the liver. This invasive test does carry a small yet significant risk of complications and is not available outside specialised liver centres. Raised pressure within the liver is also associated with changes in the microorganisms within the gut. This leads to increased infective complications among patients with liver cirrhosis. We aim to non-invasively measure the pressures within the liver using Magnetic Resonance Imaging (MRI). We will recruit 49 patients with chronic liver disease who have had liver pressure measurements as part of their routine clinical assessment. The participants will attend the Biomedical Research Unit and the MR Centre for a single 2-hour visit. We will also collect blood, urine and stool samples from them. The diagnostic accuracy of the quantitative MRI techniques will be validated against the pressures obtained via the invasive test. The quantitative MRI techniques will also correlated with biomarkers of liver injury obtained from blood and urine samples. The stool sample obtained will be used to characterise the gut microorganisms in these patients.

2) Compensated Cirrhosis study in Nottingham (3CN)

3) STOP HCV Cirrhosis study Cirrhosis is a distinct pathological entity resulting from chronic liver injury and specifically liver fibrosis. 

The progression of fibrosis to cirrhosis represents a change in morphology, haemodynamics and function of the liver. The natural history of cirrhosis is broadly divided into a compensated phase, which is largely asymptomatic, and a decompensated phase classically associated with the development of ascites, hepatic encephalopathy, variceal haemorrhage and jaundice. The transition from compensation to decompensation represents a landmark in the progression of disease and there are markedly different survival times after the development of liver cirrhosis. The availability of non-invasive biomarkers potentially allows greater stratification of prognostic information. A number of studies have shown that biomarkers at baseline predict liver related events 5-10 years later across a range of liver diseases. However liver disease is a dynamic process and thus the serial measurement of biomarkers, with subsequent refinement, will allow better stratification of patients who will 

  1. Progress to a clinical event 
  2. Remain stable with preservation of stable liver function and 
  3. Show regression to improved liver function.

The phenotyping and collection of baseline samples within HCV Research UK in combination with serial sample collection in The STOP-HCV cirrhosis study presents a unique opportunity to perform a comprehensive analysis on prognosis. The following types of data will be incorporated into the models :

  1. Clinical data – collected as part of routine care which is available within the Clinical research databases (HCV Research UK and STOP - HCV cirrhosis database) 
  2. Biomarker assays will include serum markers of fibrosis , validated panel marker algorithm and experimental biomarkers. 
  3. Host genetic markers 
  4. Viral sequencing

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guruprasad-aithal Professor Guruprasad Aithal Biography Professor Guruprasad P. Aithal graduated with MBBS from Kasturba Medical College, Manipal, MD (Internal Medicine) from Bangalore Medical College, Bengaluru, India and completed his specialist training in Gastroenterology in the Northern…