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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis; Liver Fibroses; Cystic Fibrosis Liver Disease

• Study Type: Observational
• Enrollment (Actual): 157

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M23 9LT
    • Wythenshawe Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population will be selected from the Manchester Adult Cystic Fibrosis Centre.

For the initial stage of the study 200 patients will be selected who are attending for their annual reviews. At this stage they will be consented, have bloods taken and FibroScan performed.

From this initial cohort, they will be classified into presence and absence of liver disease based on current guidelines. From this 20 patients from each group along with 20 healthy volunteers will then undergo MRI scan.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients with cystic fibrosis related liver disease; Patients with cystic fibrosis, who meet the criteria for diagnosis of liver disease according to the European Cystic Fibrosis Society best practice guidelines
Patients without cystic fibrosis related liver disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic criteria of CFLD	Number of participants that would be diagnosed with cystic fibrosis related liver disease according to the current European CF guidelines.	2 years
Using FibroScan as a tool to increase detection of CLFD	Number of participants that would be diagnosed with cystic fibrosis related liver disease with the addition of FibroScan to the diagnostic criteria	2 years
Using Biomarkers as a tool to detect CFLD	Number of participants with a diagnosis of CFLD that have an increase in serum biomarker values for known biomarkers of liver fibrosis.	2 years
Using MRI scan as a tool to detect CFLD	Number of participants with a diagnosis of CFLD that show an increase in fibrosis on their MRI scan.	2 years

Collaborators and Investigators

• Sponsor: Manchester University NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2019
• Primary Completion (Actual): June 21, 2023
• Study Completion (Actual): June 21, 2023

Study Registration Dates

• First Submitted: February 11, 2020
• First Submitted That Met QC Criteria: February 19, 2020
• First Posted (Actual): February 20, 2020

Study Record Updates

• Last Update Posted (Actual): May 1, 2024
• Last Update Submitted That Met QC Criteria: April 30, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Liver Diseases; Fibrosis; Liver Cirrhosis; Cystic Fibrosis
• Other Study ID Numbers: B00306

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No