Understanding PFIC Naming:
Looking Beyond the Numbers
By Chunyue Yin, Ph.D
What Is PFIC?
PFIC stands for Progressive Familial Intrahepatic Cholestasis. It’s a group of rare liver conditions that make it hard for the liver to get rid of bile—a fluid that helps digest fats in food. These conditions are caused by changes (mutations) in certain genes and usually show up in babies or young children.
Normally, bile flows from liver cells into small tubes called bile ducts, and then into the intestine. But in PFIC, this flow is blocked or slowed down. When bile can’t drain properly, it builds up inside the liver. This buildup is toxic—it irritates and damages liver cells over time. Think of it like a clogged drain: if the waste can’t leave, it starts harming the system. That’s why PFIC can lead to serious liver damage and, in some cases, liver failure.
Why Are PFIC Types Named with Numbers?
When doctors first discovered PFIC, they noticed that many children had similar symptoms—mainly problems with bile flow. As scientists learned more, they found that different genes were causing these problems. So, they started naming the types in the order they were discovered:
- PFIC1 is linked to the ATP8B1 gene (affects protein FIC1)
- PFIC2 is linked to the ABCB11 gene (affects protein BSEP)
- PFIC3 is linked to the ABCB4 gene (affects protein MDR3)
As genetic testing improved, more PFIC types were found in the past 10 years. Today, there are 13 known PFIC subtypes, according to OMIM.org, a website that tracks genetic conditions. The actual list of genes that have been connected to PFIC-like symptoms is even longer.
| Disease | Affected Gene | Affected Protein |
|---|---|---|
| FIC1 deficiency (PFIC1) | ATP8B1 | FIC1 |
| BSEP deficiency (PFIC2) | ABCB11 | BSEP |
| MDR3 deficiency (PFIC3) | ABCB4 | MDR3 |
| TJP2 deficiency | TJP2 | TJP2 |
| FXR deficiency | NR1H4 | FXR |
| SLC51A deficiency | SLC51A | SLC51A |
| Disease | Affected Gene | Affected Protein |
|---|---|---|
| USP53 deficiency | USP53 | USP53 |
| KIF12 deficiency | KIF12 | KIF12 |
| ZFYE19 deficiency | ZFYVE19 | ZFYE19 |
| MYO5B deficiency | MYO5B | Myosin 5B |
| SEMA7A deficiency | SEMA7A | SEMA7A |
| VPS33B deficiency | VPS33B | Vps33 |
Stay tuned for detailed review of each subtype in future posts!
Why the Numbers Don’t Tell the Whole Story
PFIC isn’t just one disease—it’s a group of different conditions that all affect bile flow in children. But each type of PFIC can look very different: some types only affect the liver, while others can affect other parts of the body. Even within the liver, different types of PFIC damage different kinds of liver cells or different steps in bile formation and flow.
These differences matter a lot when it comes to treatment. That’s why doctors don’t just look at the PFIC number—they focus on which gene is affected. Knowing the exact gene helps doctors choose the best treatment plan.
What Researchers Are Doing
Researchers study each gene to understand how it works in the liver and what goes wrong when it’s mutated. This helps them find new treatments—like medicines that fix the gene’s function or protect the liver from damage caused by specific mutations.
Because of this, some doctors and scientists prefer to name PFIC types based on the protein that’s missing or not working properly—like BSEP deficiency or MDR3 deficiency—instead of using numbers.
Final Thoughts
If you or your child has PFIC, it’s important to know that the name or number of the subtype is just the beginning. What really matters is understanding the specific gene involved, the type of mutation the patient has, and how it affects the liver. That’s what guides treatment and research—and gives hope for better therapies in the future.
About Chunyue Yin
Chunyue Yin, Ph.D, is a liver researcher and Associate Professor at the University of Cincinnati. She co-directs the Center for Undiagnosed and Rare Liver Disease and leads the Yin Research Lab. Her lab’s current focus is on inherited chronic intrahepatic cholestasis, with two primary research goals:
- Understanding how known gene mutations cause cholestasis, using zebrafish and mouse models.
- Discovering new disease-causing genes to improve diagnosis and enable personalized treatment strategies.
