Primary Biliary Cholangitis (PBC) isn’t just another liver disease. It’s a slow, silent attacker that targets the tiny bile ducts inside your liver, leading to buildup of toxic bile, scarring, and eventually, liver failure. For decades, the only real treatment was ursodeoxycholic acid (UDCA). But things changed dramatically in 2024 and 2025. The drug that once seemed like a miracle - obeticholic acid - was pulled from the market. And two new options, seladelpar and elafibranor, stepped in. If you or someone you care about has PBC, you need to know what’s working now - and what’s not.
What Exactly Is Primary Biliary Cholangitis?
PBC is an autoimmune disease. That means your immune system, which should protect you, turns against your own body. In PBC, it attacks the bile ducts in your liver. These ducts normally carry bile - a digestive fluid - from your liver to your intestines. When they’re damaged, bile backs up, poisons liver cells, and causes inflammation and scarring. Over time, this can lead to cirrhosis and liver failure.
It mostly hits women between 30 and 65. About 9 out of 10 patients are female. The exact cause isn’t known, but genetics play a role. People with certain gene variants - like HLA-DR8, IL12A, and STAT4 - are more likely to develop it. Environmental triggers, like urinary tract infections caused by E. coli, might set it off in those who are genetically at risk.
Many people don’t feel sick at first. Symptoms like fatigue and itching (pruritus) often show up years after the damage has started. By the time jaundice or abdominal pain appears, the disease is already advanced. That’s why blood tests are so important. High levels of alkaline phosphatase (ALP) and anti-mitochondrial antibodies (AMA) are the hallmarks of PBC.
The Old Standard: Ursodeoxycholic Acid (UDCA)
UDCA has been the first-line treatment since the 1990s. It’s cheap, safe, and has been used for over 40 years. Doctors still start every new PBC patient on it. The dose is 13-15 mg per kilogram of body weight, taken daily.
How does it work? UDCA replaces the harsh, toxic bile acids in your liver with a gentler, more water-soluble version. It helps flush out the bad stuff and reduces inflammation. It also seems to calm down the immune system’s attack on bile ducts.
But here’s the problem: it doesn’t work for everyone. About 35% of patients don’t respond well. That’s defined by the Barcelona Criteria - if your ALP stays above 1.67 times the normal upper limit after 12 months of full-dose UDCA, you’re considered a non-responder. And non-responders have a much higher risk of needing a liver transplant or dying. Studies show 10-year survival without transplant is 87% for responders, but only 69% for non-responders.
So UDCA is still essential - but it’s not enough for a big chunk of patients. That’s where the new drugs come in.
The Game Changer: Seladelpar (Livdelzi)
Approved by the FDA in December 2024, seladelpar - sold as Livdelzi - is now the preferred second-line treatment. It’s a selective PPAR-δ agonist, meaning it targets a specific receptor involved in bile acid regulation and inflammation.
The Phase 3 RESPONSE trial showed impressive results. After one year, 70% of patients on seladelpar saw their ALP drop by at least 15%, compared to just 20% on placebo. Even more striking: 42% achieved full ALP normalization (below 1.5 times the upper limit), versus only 6% on placebo. That’s a huge jump.
It also helped with itching - the most miserable symptom of PBC. Patients reported a 45% reduction in itching scores, while placebo saw only a 15% drop. That’s life-changing for people who lose sleep and can’t focus because of constant scratching.
There’s a catch. About 25% of patients get worse itching at first, especially in the first two weeks. But in 92% of those cases, it improves by week 8. That’s why doctors start with 5 mg daily and bump up to 10 mg after four weeks. You can’t just jump to the full dose.
Real-world data from 396 patients shows 85% stayed on seladelpar after 12 months. That’s higher than the old drug, obeticholic acid, which had a 62% continuation rate. And 73% of people who switched from OCA to seladelpar saw their ALP drop by 15% or more.
The Alternative: Elafibranor (Iqirvo)
Elafibranor, approved in November 2024, is a dual PPAR-α/δ agonist. It works on two receptors at once, which gives it a slightly different profile than seladelpar.
In the ELATIVE trial, 56% of patients on elafibranor achieved a composite biochemical response - meaning ALP dropped by at least 15% AND bilirubin stayed normal. That’s compared to just 12% on placebo. ALP normalization hit 21%, which is good - but not as high as seladelpar’s 42%.
It also helped with itching, reducing scores by 38%. That’s still better than placebo, but not quite as strong as seladelpar. One advantage? It’s taken as a single 80 mg pill once a day - no titration needed.
But it has its own risk: elevated creatinine. About 18% of patients saw their kidney marker rise. That doesn’t always mean kidney damage, but it does mean you need regular blood tests to monitor it.
Elafibranor also improves lipid levels. It lowers triglycerides by 24%, while seladelpar only drops them by 8%. For patients with metabolic syndrome or fatty liver, that’s a bonus.
Why Obeticholic Acid (Ocaliva) Was Withdrawn
Before 2025, obeticholic acid (Ocaliva) was the go-to second-line drug. It was approved in 2016 and worked by activating the farnesoid X receptor (FXR), which helps regulate bile acid production.
It looked promising at first. In the POISE trial, 46% of patients reached the ALP target. But long-term data told a different story. By year four, only 28% were still responding. Worse, it caused severe itching in 56% of patients - and 5% had to stop taking it because of it.
The real red flag came from safety data. A 2024 FDA analysis found 8.9% of Ocaliva users had serious cardiovascular events - like heart attacks or strokes - compared to 5.2% on placebo. For patients with advanced liver disease (Child-Pugh B or C), the risk of death was 78% higher.
In September 2025, the FDA pulled Ocaliva from the market. The Gastrointestinal Drugs Advisory Committee voted 12-3 to remove it. The message was clear: the risks outweighed the benefits, especially for people with moderate to severe itching or advanced liver damage.
What Doctors Recommend Now
The latest guidelines from AASLD and EASL (updated October 2025) are clear:
- Start everyone on UDCA at 13-15 mg/kg/day.
- Check ALP after 12 months. If it’s still above 1.67x ULN, move to second-line.
- For second-line: seladelpar is preferred - especially if itching is severe.
- If seladelpar isn’t available or tolerated, use elafibranor.
- Fibrates (like fenofibrate) can be used off-label if neither is an option, but they’re less effective.
Monitoring is critical. ALP should be checked every 3 months during treatment changes, then every 6 months once stable. It’s not about one number - it’s about the trend. A sustained drop of 15% or more, even without full normalization, still lowers your risk of liver failure.
Dr. David Jones from Mayo Clinic says: “ALP normalization is the ideal goal, but even a 40% reduction gives you a real survival advantage.” A 2024 meta-analysis of over 12,000 patients found every 10% drop in ALP meant a 7.2% lower risk of death or transplant.
What Patients Are Saying
Real people are sharing their experiences. In a survey of 1,247 PBC patients by MyPBCteam in August 2025, 68% of those who switched from Ocaliva to seladelpar said their quality of life improved within eight weeks. Many reported sleeping better, being able to work without distraction, and finally enjoying meals again.
But it’s not perfect. About 22% of switchers said itching got worse during the first few weeks of seladelpar. That’s why patience and close doctor follow-up are key. Most patients who stick with it past week 8 feel much better.
Cost is another issue. Seladelpar and elafibranor are expensive. Medicare requires proof of UDCA failure and ALP >1.67x ULN before covering them. About 28% of seladelpar prior authorizations get denied. That’s a huge barrier for many.
What’s Coming Next
The pipeline is active. Twelve new drugs are in development. Setanaxib, which blocks a protein linked to liver scarring, is in Phase 3 and could be available by 2027. Cenicriviroc, a drug that reduces inflammation, is also being tested. And there’s even a fecal microbiota transplant capsule, VE-202, being studied - because gut health might play a role in PBC.
The FDA is also changing how they measure success. In September 2025, they accepted the PBC-40 PRO instrument - a patient-reported outcome tool - as a valid endpoint for future trials. That means doctors will soon be looking not just at blood tests, but at how patients actually feel: their energy, sleep, itching, and daily function.
The global PBC drug market is expected to hit $2.1 billion by 2030. But affordability will be the biggest challenge. Right now, 40% of commercially insured patients pay over $500 a month out of pocket for the new drugs. Without better pricing, many won’t get the care they need.
Bottom Line: What You Need to Do Now
If you have PBC:
- Stay on UDCA unless your doctor says otherwise.
- Get your ALP checked every 3-6 months.
- If you’re not responding after a year, talk to your hepatologist about seladelpar.
- Don’t panic if itching gets worse at first - it often improves.
- Ask about financial assistance programs - many manufacturers offer them.
- Use resources like the PBC Foundation’s Treatment Navigator to understand your options.
PBC is no longer a death sentence. With the right treatment, most people live full, active lives. The tools are better than ever. But you have to be proactive. Know your numbers. Ask questions. And don’t settle for a treatment that leaves you miserable. The old days are over. The new era of PBC care is here - and it’s working.
