Primary Biliary Cholangitis Treatment: What Works in 2025

Primary Biliary Cholangitis (PBC) isn’t just another liver condition. It’s a slow-burning autoimmune disease where the body attacks its own bile ducts, leading to bile buildup, liver damage, and eventually cirrhosis if left unchecked. About 9 out of 10 people diagnosed are women, usually between 30 and 65. For decades, the only real treatment was ursodeoxycholic acid (UDCA)-a bile acid that helps flush out toxins. But now, in 2025, the game has changed. Two new drugs have joined the fight, and one older one was pulled off the market entirely. If you or someone you know has PBC, here’s what you actually need to know about treatment today.

UDCA is still the first step-every time

Even with new options, UDCA hasn’t been replaced. It’s still the starting point for every newly diagnosed patient. Taken daily at 13-15 mg per kilogram of body weight, UDCA works by replacing toxic bile acids with gentler ones, helping the liver drain properly and calming down the immune attack. Studies show it works well for 60-65% of people. Those who respond have an 87% chance of surviving 10 years without needing a transplant. Those who don’t? That number drops to 69%.

But here’s the catch: if your alkaline phosphatase (ALP) levels haven’t dropped by at least 40% after a full year on UDCA, you’re considered a non-responder. That’s about 35% of patients. For years, there wasn’t much else to do. Now, there are two solid options.

The old drug that’s no longer an option: Ocaliva

Obeticholic acid (Ocaliva) was approved in 2016 as the first real alternative to UDCA. It worked by activating a receptor in the liver that helped reduce bile acid production. In trials, it helped 46% of patients reach target ALP levels. But over time, the downsides piled up. Severe itching affected more than half of users. Some people had to stop taking it because of it. Worse, long-term data showed a higher risk of serious liver complications and even death in patients with advanced disease.

In September 2025, the FDA pulled Ocaliva from the market. The decision wasn’t made lightly-it followed a vote by an independent advisory panel and years of safety reviews. The message was clear: the risks no longer balanced out the benefits. If you were on Ocaliva, you’re not alone. Many switched to newer drugs. And for most, the switch meant better symptoms and fewer side effects.

Seladelpar (Livdelzi): The new frontrunner

Seladelpar, sold as Livdelzi, got FDA approval in December 2024. It’s a targeted drug that activates the PPAR-delta receptor, which helps reduce inflammation and bile acid buildup. In the Phase 3 RESPONSE trial, 70% of patients saw their ALP drop by at least 15%-compared to just 20% on placebo. Even better, 42% reached full ALP normalization, meaning their levels were back to near-normal range.

What really sets seladelpar apart is how it handles itching-the most miserable symptom of PBC. About 70% of patients deal with constant, disruptive itching. In trials, seladelpar reduced itching scores by 45%, while placebo only brought it down by 15%. That’s not just a number-it’s life-changing. People report sleeping better, not scratching through the night, and being able to focus at work again.

There’s a catch: about 25% of people get worse itching in the first two weeks. That’s why doctors start with 5 mg daily, then bump it to 10 mg after four weeks. Most of those who feel worse at first find relief by week 8. Real-world data from over 390 patients shows 85% stayed on seladelpar after a year, even after switching from Ocaliva.

Elafibranor (Iqirvo): The balanced alternative

Elafibranor, branded as Iqirvo, got approved in November 2024. It’s a dual PPAR-alpha/delta agonist, meaning it works on two pathways at once. It’s simpler to take-just 80 mg once a day, no titration needed. In trials, 56% of patients hit the target ALP reduction, and 21% reached full normalization. That’s solid, but not quite as strong as seladelpar.

Where elafibranor shines is in its side effect profile. It doesn’t worsen itching the way seladelpar sometimes does. It also helps lower triglycerides by 24%, which is a bonus for patients with metabolic issues like fatty liver or high cholesterol. But it’s not perfect. About 18% of users saw a rise in creatinine, a marker of kidney function. That doesn’t mean kidney damage-it’s just something your doctor needs to monitor.

For patients who can’t tolerate the initial itching spike with seladelpar, or who need help with lipid levels, elafibranor is a smart choice. It’s not the most powerful, but it’s reliable and easier to manage.

What about fibrates?

Fibrates-drugs like fenofibrate and bezafibrate-aren’t officially approved for PBC. But they’ve been used off-label for years, especially in Europe. They work by activating PPAR-alpha, which helps clear bile acids and reduce inflammation. Some studies show they can help patients who don’t respond to UDCA, especially when combined with it.

They’re cheap, widely available, and have decades of safety data from use in cholesterol management. Many hepatologists still consider them a viable third-line option, especially where newer drugs are hard to access or too expensive. But they’re not as powerful as seladelpar or elafibranor in large-scale trials.

Monitoring and what success really looks like

There’s no single magic number that means you’re cured. But ALP levels are your best guide. The goal isn’t always perfect normalization. The 2025 guidelines say that a sustained 40% drop in ALP-even if it doesn’t hit normal range-still cuts your risk of liver failure or transplant by a significant amount.

Doctors check ALP every 3 months when you start a new drug, then every 6 months once you’re stable. If ALP stays above 1.67 times the upper limit after 12 months on UDCA, it’s time to add a second drug. Waiting too long increases your risk of scarring.

It’s not just about numbers anymore. The FDA now accepts patient-reported outcomes like the PBC-40 PRO questionnaire as official endpoints in trials. That means how you feel-your energy, your sleep, your ability to live normally-is now part of the treatment equation.

What’s next? The pipeline and the future

The PBC drug market is heating up. Twelve new drugs are in development. Setanaxib, which targets oxidative stress, is in Phase 3 and could be available by 2027. Fecal microbiota transplants (VE-202) are being tested to reset gut-liver communication. There’s even a new FXR agonist called tropifexor that doesn’t cause the same itching problems as older drugs.

But access is still a problem. Medicare and many insurers require proof of UDCA failure and high ALP before covering seladelpar or elafibranor. Denial rates for prior authorization hover around 28%. That means some patients wait months or pay out-of-pocket-sometimes over $500 a month.

What’s clear is this: PBC treatment has moved from “manage symptoms” to “target disease progression.” We’re no longer just slowing things down-we’re trying to reverse damage before it’s too late. The tools are better. The goals are clearer. And for the first time, patients have real choices.

What to do next

If you’ve been diagnosed with PBC:

• Start UDCA right away-don’t delay.
• Get your ALP checked at 6 and 12 months. If it hasn’t dropped enough, talk to your hepatologist about second-line options.
• If you’re on Ocaliva, switch to seladelpar or elafibranor as soon as possible. Most patients feel better within weeks.
• Track your symptoms, not just your labs. Use tools like the PBC-40 PRO to document how you’re feeling.
• Ask about financial assistance programs. Gilead and Genfit both offer co-pay cards and patient support services.

PBC isn’t curable yet. But it’s no longer a death sentence. With the right treatment, many people live full, active lives for decades. The key is acting early-and knowing what options are actually available today.