The Use of Novel Diagnostic Tools to Increase Detection of Early Fibrosis in Cystic Fibrosis Related Liver Disease to Improve Clinical Management

The Use of Novel Diagnostic Tools to Increase Detection of Early Fibrosis in Cystic Fibrosis Related Liver Disease to Improve Clinical Management

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. Treatment options are limited with liver transplant the only curative option. Though potentially life-saving, it has 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.

This study will use multi-modality testing, including imaging techniques such as FibroScan, MRI scan and blood tests (biomarkers), to diagnose those with liver scarring and use this to better categorise disease.

Inclusion Criteria:

1. Male or female > 18 years of age

2. Females will be non-pregnant and non-lactating* (for MRI scan only)

3. 20 patients with confirmed diagnosis of CF, 20 with CFLD and 20 healthy volunteers

   • Women of childbearing potential (i.e. not surgically sterilised or <1 year post menopause) will be required to:

1. Confirm they are not currently breastfeeding 2. Undergo a serum pregnancy test (serum β-HCG)

Exclusion Criteria:

1. Contraindication to magnetic resonance imaging scanning (including claustrophobia) or gadolinium-based contrast agent
2. eGFR < 50 mL/min/1.73m2
3. Pregnant or breast-feeding women.
4. Any other condition, which in the opinion of the research team may put participants at risk during the study.