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PBC Extrahepatic Issues
FAQs on PBC Extrahepatic Issues: Symptom Management and Advances in Treatment

Released: May 01, 2025

Expiration: April 30, 2026

Aparna Goel
Aparna Goel, MD
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Key Takeaways
  • Fatigue and pruritus affect many people with PBC and should be actively managed.
  • Fracture risk should be considered in people with PBC.

Although slowing disease progression is a key goal in managing primary biliary cholangitis (PBC), addressing extrahepatic symptoms that affect quality of life is equally important. These symptoms need to be managed independently of the biochemical response and require a separate evaluation and discussion to develop a treatment strategy.

The most common symptoms that affect quality of life for people with PBC are pruritus and fatigue. Studies show that many people with PBC experience fatigue, and more than 80% experience pruritus at some point.

Below are some common questions about extrahepatic issues in PBC. 

How do you differentiate cholestatic pruritus vs pruritus from other causes?
Cholestatic pruritus, or pruritus caused by a biliary disease, has a typical presentation pattern. The itch will often primarily affect the palms and soles, and it is generally much worse at night. It is not usually associated with a rash, although sometimes the excoriation marks and the lichenification is so severe that it almost presents as rash.

If a person with PBC has hives, urticaria, and eczema patches, then the pruritus might not be cholestatic. In such cases, it might be worth collaborating with a dermatologist. In my practice, I check serum bile acid levels if there is diagnostic uncertainty regarding the etiology of pruritus.

Nevertheless, since pruritus is so common in PBC, cholestatic pruritus is often the most likely etiology.

Is there a correlation between lowering bile acid with peroxisome proliferator-activated receptor (PPAR) agonists and outcomes?
The exact effect of lowering bile acids is unclear right now, and bile acid levels are not always reported as part of PBC clinical trials.

However, one study suggested that seladelpar lowers levels of interleukin (IL)-31, an interleukin thought to be associated with pruritus.

What we do know is that PPAR agonists elafibranor and seladelpar, which are second-line therapy for PBC, might have the potential to improve pruritus, as shown in some of the pruritus outcomes measured in their phase III trials.

This contrasts with first-line ursodiol, which may normalize alkaline phosphatase levels but does not alleviate pruritus and the second-line farnesoid X receptor (FXR) agonist obeticholic acid, which was associated with treatment-emergent pruritus.

What was the fracture risk in PPAR studies, and what is known about how PPARs affect bones?
In general, there is a higher incidence of bone fracture in patients with PBC because the disease tends to affect women in their 40s-60s, a population that is already predisposed to osteopenia and/or osteoporosis.

In clinical trials of both new second-line drugs, there was an increased fracture rate, with elafibranor at 6% and seladelpar at 4%, compared with 0% for placebo. 

To me, this suggests that it is imperative for people with PBC to have up-to-date bone density scans and to receive appropriate treatment if they have osteopenia or osteoporosis. PBC is also associated with low vitamin D and bone turnover, so vitamin D supplementation is recommended for all individuals with PBC.  

Your Thoughts
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