Investigating better diagnostic tools for CFLD V1.0
Research type
Research Study
Full title
The use of novel diagnostic tools to increase detection of early fibrosis in Cystic Fibrosis related liver disease to improve clinical management.
IRAS ID
243985
Contact name
Varinder Athwal
Contact email
Sponsor organisation
Manchester Foundation Trust
Duration of Study in the UK
2 years, 0 months, 28 days
Research summary
Study summary:
Cystic Fibrosis (CF) is a genetic condition which affects 1 in 2500 newborn infants and is the commonest genetic condition in the UK. 1 in 25 of the white population carry the mutation. The genetic defect prevents the movement of fluids from cells, leading to thickened secretions and injury. With improvements in treatments from the commonest organ affected, the lungs, patients born with CF now can expect to live into their 40s with more than 60% living past 16. Though better, more can be done. As treatments from lung complications have improved, the management of liver disease (second commonest organ involved) remains unchanged for a considerable time. The only treatment option remains a liver transplant for those with the severest disease. Though it can be life changing, it has multiple risks and an organ shortage means alternative treatment options are desperately needed.Identifying those with or at risk of Cystic Fibrosis related liver disease is difficult due to inadequate diagnostic tools. Routine blood tests are unreliable; therefore specific blood tests to identify scarring of the liver (biomarkers) are urgently needed. Ultrasound scan, the recommended diagnostic investigation, is only accurate in identifying the late stages of liver disease. For new therapies to be most effective we need to be able to identify patients at a much earlier stage.
My research will look to find better methods, including imaging techniques such as FibroScan and MRI scan and blood tests (biomarkers), to diagnose those with liver scarring and use this as a way to find why some get scarring whilst others don't.
Summary of study results:
BACKGROUND Current diagnostic tools are limited in their ability to diagnose cystic fibrosis liver disease (CFLD) as disease is often focal in nature. Magnetic resonance extracellular volume quantification (MRI ECV) in the liver may have diagnostic utility in CFLD as a larger area of the liver is assessed and can be performed using equipment readily available in clinical practice on a fast MRI protocol.
METHODS
Healthy volunteers (HV), CF participants with no liver disease (CF-noLD) and CF participants with cirrhosis (CF-C) aged 18 years and above had MRI ECV measured using a 3T Siemens scanner. An additional retrospective analysis was performed to calculate MRI ECV in individuals who had available images obtained using a 1.5T Siemens scanner from a previous study.
RESULTS
16 individuals had MRI ECV measured using a 3T Siemens scanner. Mean (SD) MRI ECV was 0.316 (0.058) for HV (n=5), 0.297 (0.034) for CF-noLD (n=5) and 0.388 (0.067) for CF-C (n=6). Post-hoc analysis showed a significant difference between CF- noLD and CF-C (p=0.046). Of 18 individuals with available images using a 1.5T scanner, mean (SD) MRI ECV was 0.269 (0.048) in HV (n=8), 0.310 (0.037) in CF- noLD (n=8) and 0.362 (0.063) in CF-C (n=2).
CONCLUSIONS
Liver MRI ECV quantification was feasible in adults with CF with concordance of results between 1.5T and 3T obtained images suggesting applicability across different types of MRI scanner. A higher MRI ECV was demonstrated in CF participants with cirrhosis suggesting potential utility as a diagnostic tool for those with advanced CFLD. Further evaluation in larger cohorts is warranted.REC name
North West - Greater Manchester West Research Ethics Committee
REC reference
18/NW/0827
Date of REC Opinion
10 Jan 2019
REC opinion
Further Information Favourable Opinion