The Cystic Fibrosis Foundation (CFF) published new guidelines for cystic fibrosis-associated liver disease in 2024. This marked the first update in 25 years and included several important changes, such as:
New classifications of CF hepatobiliary involvement (CFHBI) versus advanced CF liver disease (aCFLD)
Regular ultrasounds to detect signs of CFHBI
Regular elastography to monitor changes in CFHBI and aCFLD
Official guidance on multidisciplinary care
Although the guidelines are 2 years old, many gastroenterologists may be unaware of the changes and unprepared to implement them.
Meghana Sathe, M.D., Pediatric Gastroenterologist at Children’s HealthSM and Professor at UT Southwestern, served on the CFF guideline committee and has helped colleagues at other centers start the process of aligning with recommendations.
Below, she answers common questions about how teams should define, screen, monitor and treat liver complications in cystic fibrosis today.
How did you join the guideline committee, and who else was involved?
I was invited to join the CFF guidelines committee after years of leading the Cystic Fibrosis Center at Children’s Health and participating in DIGEST (Developing Innovative Gastroenterology Specialist Training), the CFF’s effort to train more GIs in the particulars of cystic fibrosis (CF).
The CFF guideline committee is large and multidisciplinary, including pulmonologists, gastroenterologists/hepatologists, dieticians, pharmacists and endocrinologists.
The committee also included persons with CF and liver disease, as well as family members. They participated in literature review, shared their perspectives on the evidence and proposed recommendations. And now they serve as important emissaries for educating other persons with CF and their families. The recommendations carry more weight when they are developed in collaboration with those with lived experience.
What are the new classifications for CF-associated liver disease?
The committee outlined two forms of disease:
Cystic fibrosis hepatobiliary involvement (CFHBI) describes the preliminary manifestations. It spans a wide range of indicators, including liver fibrosis <F4, increased liver stiffness by elastography <F4, cholestasis and abnormal liver imaging. A complete list is available here.
Advanced CF liver disease (aCFLD) covers the later stages of involvement and is defined as:
Nodular liver
Advanced fibrosis (F4)
Multi-lobular cirrhosis (with or without portal hypertension)
Non-cirrhotic portal hypertension
These categories bring much-needed clarity to the field. Multiple definitions of CF-associated liver disease have emerged over the years. Clearly establishing and defining CFHBI and aCFLD will ensure that teams compare apples to apples across research and follow best practices for clinical care.
What are the most important screening recommendations?
There are three:
Liver-specific physical exam performed annually
Annual bloodwork and follow-up on abnormal values. Common liver test abnormalities in CF may include elevations in serum AST, ALT, GGT and/or alkaline phosphatase.
Ultrasounds every 2 years, based on the PUSH study which found that livers with heterogeneity and coarseness had higher odds of developing aCFLD.
How should teams monitor patients with CFHBI and aCFLD?
We recommend a series of regular tests and consultations. Tests include:
(CFHBI) Annual blood testing to allow for determination of at least 1 fibrosis marker such as GPR, APRI or GGT.
(aCFLD) Screening for CF-related diabetes at the time of aCFLD diagnosis.
(both) Annual elastography to evaluate liver stiffness, which is associated with fibrosis.
With blood tests and elastography, the idea is to treat each person as their own control: Evaluate each year to look for trends and changes.
Patients with either CFHBI or aCFLD should consult with a pharmacist twice a year, to review drug-drug interactions (DDIs), including supplements. Patients with aCFLD should also see a dietitian twice a year, because these patients have two routes to malnutrition: CF causes pancreatic insufficiency and liver disease can impact bile flow; both have consequences impacting nutrient absorption.
What do the guidelines say about CFTR modulators and other treatments?
CFTR modulators have proven benefits for children with pulmonary problems. So the CFF recommends their careful use in cases where those benefits are paramount, including in liver transplant patients.
But current evidence is insufficient to recommend their use for improvement of CFHBI or aCFLD. That may change as CFTR modulators are studied further. One thing we know for sure: They should not be used in CF patients with decompensated advanced liver disease. CFTR modulators are serious drugs that place a high demand on the liver. They should be used with care and caution, routinely monitoring for any signs of drug-induced liver injury.
The other treatment recommendation worth noting is the discontinued use of ursodeoxycholic acid (UDCA) to prevent advanced liver disease in patients with CF. UDCA used to be prescribed at birth and continued thereafter. This practice has faded from use after multiple studies found that the medication fails to prevent aCFLD. Now it’s official: Don’t use UDCA to prevent/treat liver problems in CF.
How should teams go about implementing the guidelines?
Most centers are likely to find they already follow some guidelines but will have to update their practice to meet others. I recommend taking it slow: Pick one guideline. Implement and master it. Then move on to another.
At Children’s Health, we started with reclassifying our patients according to the new definitions. Then we took on a quality improvement project to implement the ultrasound and elastography recommendations. Now we are working on ensuring a thorough liver workup has been conducted for those identified with CFHBI.
Consulting with other departments is also important. I’ve met with our radiologists to discuss how to read and label imaging based on the latest guidelines to make sure we are all speaking the same language in terms of interpreting and reporting results.
Caring for kids with CF is a team effort. It’s exciting to have common standards to bring us all together to improve the lives of our patients and families.
Learn more about our Cystic Fibrosis Program at Children's Health.
