Primary biliary cholangitis (PBC) is not your typical autoimmune disease. Its triggers are similar, like your genetic makeup and things in your environment. But it doesn’t respond to medicines that target the immune system the way other autoimmune diseases do. One reason might be that by the time it’s diagnosed, liver damage from PBC is beyond the healing scope of drugs like biologics.
This means that the number of effective PBC drugs has been limited until now. But new treatments and tests can work well when first-line drugs don’t do enough.
When You Need More Than UDCA
The main goal of PBC treatment is to slow down its progression, treat symptoms, and prevent complications of the disease. Some treatments work to move trapped bile out of the liver and limit fibrosis, or scar tissue. That’s important, because scarring can lead to cirrhosis and liver failure.
The first medication you’ll likely take for PBC is ursodeoxycholic acid (UDCA), also called ursodiol. But UDCA doesn’t improve liver function tests for everyone. In fact, between 25% and 50% of people who take it don’t respond or don’t respond enough to it. This makes it more than five times more likely that their PBC will progress to cirrhosis and three times more likely that they’ll die of the disease.
You may not respond well to UDCA if:
- You’ve already had some cirrhosis, or scarring of the liver.
- Levels of gamma‐glutamyl transferase, a liver enzyme, were also very high when you were first diagnosed.
- Your body just can’t tolerate UDCA.
These are all reasons to try a second-line treatment.
The goal is not only to improve test results and reduce complications , but also address symptoms that hurt your quality of life, like intense itchiness and poor sleep. UDCA doesn’t help with these.
Second-Line Treatments: Old and New Drugs
Standard treatment for PBC is about to give way to brand-new drugs on a fast track for approval. Here’s what available now and what’s on the way:
Obeticholic acid (OCA). You may take OCA (Ocaliva) early on if you don’t get a good response from UDCA or if you can’t tolerate it. Your doctor may also use the two drugs together. OCA is part of a class of medications called farnesoid X receptor agonists. It both lowers the amount of bile your liver makes and helps push it out. On its own or with UDCA, OCA helps improve liver function and slow fibrosis. But it may make PBC itching worse.
In some people, this medicine can make liver damage worse. If you have cirrhosis, you should not take Ocaliva.
Budesonide. There’s some research that shows that this corticosteroid helps lower alkaline phosphatase, or ALP, a liver enzyme that’s at higher levels in people with PBC. But concerns over side effects have kept it from being a primary option. These include weight gain, dizziness, headache, and joint pain. With long-term use, it can cause osteoporosis and vision changes.
Fibrates. These drugs are part of a drug class called PPAR agonists because they fight proteins known as peroxisome proliferator-activated receptors or PPARs. PPARs have a link to many metabolic conditions, like high triglycerides and cholesterol.
Fibrates specifically target the subtype called PPAR-alpha. Research shows that they can help:
- Improve your response to UDCA
- Lower liver enzyme levels
- Reduce bilirubin
- Tamp down inflammation
- Reduce cirrhosis risk
- Calm itching
- Ease fatigue
Studies show that a triple approach with fibrates, UDCA, and OCA can work even better. Because fibrates can damage the liver, you shouldn't take these medicines if you have severe cirrhosis.
Fenofibrate (Tricor) is a fibrate drug that doctors may prescribe off label for PBC symptoms. Researchers need to study this drug more, but it may ease itching and liver inflammation when you take it with UDCA.
New PPAR Agonists. Researchers have built on the benefits of PPAR agonists to create new PBC drugs that target various PPAR subtypes:
Elafibranor (Iqirvo) is a different kind of PPAR agonist that you take along with UDCA if you don't respond to UDCA alone. It targets PPAR-alpha and -delta. In its clinical trials, just over half the people being studied achieved normal bilirubin levels and a lower ALP level – 15% reached a normal ALP. The drug also lowered total and LDL cholesterol and triglycerides. The most common side effects were belly pain, nausea and vomiting, and diarrhea.
Seladelpar(Livdelzi) is a PPAR-delta agonist. In clinical trials, it brought bilirubin levels down to normal and lowered ALP by 44% on average. About 15% of the people studied reached normal levels. It also improved itchiness for nearly all those taking part. Most found that their itching no longer kept them up at night, which in turn helped ease their fatigue. Side effects were belly pain and distention and nausea.
Third-Line Treatment: Liver Transplant
When medications don’t slow PBC, it can lead to cirrhosis and keep your liver from working properly. If you’re at risk for liver failure or have early signs, you may be a candidate for a liver transplant to help prolong your life.
Monitoring Remains a Must
As you live with PBC, expect that your care team will watch your health closely for the rest of your life. They’ll do this with tests geared to your specific situation and symptoms.
Your doctor ran blood tests that measure bilirubin and liver enzymes after you started UDCA. These let them know that it wasn’t working well enough and you should start second-line treatment. You’ll continue to have these blood tests to see how well your new medications are working.
Noninvasive imaging tests, like transient elastography and magnetic resonance elastography, are also important. Medications do help slow down PBC. But studies show that even so, about half those with early-stage PBC advance to a more severe stage within 5 years. Regular imaging tests can detect changes like advancing fibrosis early on.
Your doctor will also use these imaging tests to look for portal hypertension. This is high pressure in the blood vessels of your liver caused by fibrosis. It’s dangerous because it can cause many complications.
Show Sources
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