Cystic Fibrosis-related Liver Disease

Cystic Fibrosis (CF) is a common condition caused by genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR gene creates the protein involved in the production of sweat, digestive fluids, and mucus with the goal of maintaining a balance of water and salt in cells. With cystic fibrosis, the CFTR protein functions abnormally. Rather than moving water in and out of cells, the water becomes trapped, causing mucus outside of the cell to thicken and accumulate [1].CF can affect many organs including the lung, pancreas, and liver. When a patient develops liver disease due to cystic fibrosis, clinicians use the term CF related liver disease.

The liver has many important functions in the body. Bile is an important digestive juice that is made in the liver, stored in the gallbladder, and enters your small intestine to help with digesting the fats in our food. The bile ducts carry bile from the liver to the intestine.  In CF, the cells that line the bile ducts are affected, which leads to bile not draining properly. The blockage of bile ducts can interfere with the liver’s ability to clear toxins from the blood, leading to inflammation, which can damage the liver and cause scarring over time. Advanced liver disease can result in permanent scarring of the liver, otherwise known as cirrhosis.

There are about 30,000 children and adults in the US with CF, with about 1,000 new cases annually. 30-40% of patients with CF will have some liver disease, with 5-10% of these patients having more advanced liver disease [2]. There is a wide spectrum of liver disease which may include abnormal liver labs, fatty liver, liver fibrosis, and liver cirrhosis with or without portal hypertension.

Often, the earliest signs of CF liver disease are not noticed by the patient.  They can include the development of abnormal liver laboratory testing, or abnormalities seen on ultrasound. 

When CF liver disease becomes advanced, the following signs can be seen:       

• High direct or “conjugated” bilirubin level. This can cause jaundice or yellowing of the skin or eyes.
• Larger than normal liver
• Signs or symptoms of portal hypertension symptoms. This happens when the blood flowing into the liver meets resistance.
  • Larger than normal spleen
  • Enlarged blood vessels (varices) in the esophagus
  • Accumulation of fluid in the abdomen

There is not just one test that can diagnose CF liver disease. Your doctor may do a few or all of these tests below to obtain more information.

• Laboratory tests: Bloodwork can be done to assess for liver function and liver inflammation.
• Physical Exam: The doctor and/or advanced care provider will feel for any for enlargement of the liver or spleen, and overall physical assessment.
• Abdominal Ultrasound: This is a painless way to look at the abdominal organs. There is no radiation involved with an ultrasound. This can look at the texture and size of the liver, as well as the gallbladder and spleen. It cannot diagnose CF liver disease alone but can give your doctor more information.
• Liver Biopsy: The child is given anesthetic medicine for the procedure. A needle is then passed into the liver to get a small sample of the tissue. A pathologist will examine the liver tissue underneath a microscope. The microscopic examination of the biopsy may identify other causes of liver disease as well. 

There are no treatments to prevent or cure CF liver disease at this time. Right now, treatment involves being regular follow up by a doctor specializing in liver disease (known as a hepatologist). The doctor will monitor for symptoms of CF liver disease. There are some medicines, such as ursodiol, which might help improve bile flow from the liver that your child’s doctor may want to start.

As new therapies, including those that improve the function of the cystic fibrosis transmembrane regulator protein (CFTR), become available, there will be the potential to prevent or reverse clinically significant liver disease in CF. This is why it is very important that your child is monitored for development of liver disease complications related to CF [2]. Ensuring optimal nutrition is also very important in patients with CF liver disease. 

Liver transplantation is needed in certain cases where the liver is severely scarred and not able to function properly. Liver transplantation involves surgically exchanging the sick, scarred liver with a  new liver. (see liver transplantation handout).

• CF is a genetic condition that can cause disease in organs such as the lungs, liver, and pancreas
• Patients with CF have impaired bile flow which can lead to inflammation and scarring of the liver over time
• If your child has cystic fibrosis, it is important to monitor for signs of CF related liver disease.
• The follow up by the gastroenterologist or hepatologist includes blood tests, physical exam, radiological tests (including US), and sometimes liver biopsy
• Although CF is a very common genetic condition, only a small proportion of patients will develop severe liver disease with permanent scarring of the liver
• There is currently no cure for CF liver disease, but there are some medications that may aid in improving bile flow from the liver
• More therapies will be developed in the future that may have the potential to prevent or reverse liver disease in CF

• Cystic Fibrosis Foundation (https://www.cff.org): Information for patients and their families living with CF
• The Childhood Liver Disease Research Network (https://childrennetwork.org/Clinical-Studies/Cystic-Fibrosis-Liver-Disease): Provides information on clinical studies for patients and their families and can connect them with researchers to get involved in clinical

1. Cystic Fibrosis Foundation. Basics of the CFTR Protein.
2. Flass, T. and M.R. Narkewicz, Cirrhosis and other liver disease in cystic fibrosis. J Cyst Fibros, 2013. 12(2): p. 116-24.

Editor: Athos Bousvaros, MD
September 2021