For patients with biliary atresia, there are limited treatment options available. Currently, the rare liver and bile duct condition may progress to end-stage liver fibrosis and cannot be prevented or treated with medication. The preferred line of treatment is a surgical method called the Kasai procedure. However, shares Medical XPress, researchers from Cincinnati Children’s recently used functional biliary organoids, developed using diseased tissue, to identify potentially more efficacious treatment options. Interested in checking out the full study? Take a look at Hepatology for more.
To begin, what is biliary atresia? This rare condition causes a blocked or malfunctioning biliary system in infants. Normally, bile moves through the biliary system from the liver to the gallbladder. However, in patients with biliary atresia, the bile ducts (in and outside of the liver) are scarred or blocked. This causes bile to back up, accumulate in the liver, and cause further scarring or health issues. Symptoms usually appear within 2-8 weeks following birth. Biliary atresia is slightly more likely to affect females than males. The cause of this condition is still relatively unknown. Symptoms include:
- Pale yellow, white, or gray stool
- Jaundice (yellowing of the skin and eyes)
- Dark yellow or brown urine
- Poor weight gain and/or failure to thrive
- High blood pressure
- Abdominal distention
- Abnormally large liver
- Heart or kidney malformations
- Liver scarring
- Intense itching
- Liver failure
Within their study, researchers first used diseased tissue to grow biliary organoids. This is extremely important. By using diseased tissue, researchers are able to see how the tissue works and functions firsthand, thus giving them a full understanding of how human tissue – rather than mouse models or non-human tissue – would respond to changes or treatments. According to the published study, the researchers sought to understand what mechanisms led to the development of abnormal cholangiocytes.
Once developing these organoids, researchers compared them to organoids developed using healthy liver tissue. Next, they began exploring how the two were structurally different. Findings include:
- Organoids developed using healthy tissue were made up of tightly bound cells with a protective outside layer. The way that the organoids were set up allowed them to function in different ways. In healthy patients, the epithelial cell linings prevent bile acid from irritating the biliary ducts or causing issues.
- Alternately, diseased organoids had disorganized inner and outer layers, as well as abnormally located or flipped cells. Because of this, bile acids can move through these gaps, causing cellular irritation and inflammation, as well as biliary system damage.
Thus, researchers found that cellular permeability issues could ultimately lead to liver scarring. Next, researchers explored the reason behind these issues. They found that fibroblast growth factor-2 (FGF2) and epidermal growth factor (EGF) were inactive in the diseased biliary organoids. Researchers then treated these organoids in an attempt to reactive FGF2 and EGF pathways. Through doing so, researchers found that the organoids began developing in a healthier way.
So could targeting the FGF2 and EGF pathways improve patient outcomes? Well, that’s the next step in the research! First, researchers need to evaluate human patients with biliary atresia to determine whether FGF2 and EGF are abnormal in these patients. This is crucial, as it is not enough for just the organoids to show this. Next, researchers need to determine whether current drugs exist which could fill this treatment need in infants or whether drug development is needed. Finally, clinical trials would be required to best evaluate the drug. However, having a better understanding of the potential underlying mechanisms that might lead to biliary atresia is a good first step.