Primary Biliary Cholangitis Treatment in 2025: What Works, What Changed, and What to Expect
Primary Biliary Cholangitis (PBC) isn’t just another liver condition. It’s a slow, silent disease that attacks the tiny bile ducts inside your liver, causing bile to build up and damage liver tissue over time. For decades, there was essentially one treatment: ursodeoxycholic acid (UDCA). But in 2025, the landscape has changed dramatically. The drug that once dominated PBC care-obeticholic acid-is no longer available. Two new options have stepped in, offering real hope for patients who didn’t respond to UDCA. This isn’t just a minor update. It’s a full reset in how doctors treat this autoimmune liver disease.
What Exactly Is Primary Biliary Cholangitis?
PBC is an autoimmune disease, meaning your immune system mistakenly targets your own body. In this case, it attacks the small bile ducts in your liver. Bile is supposed to flow out of the liver to help digest fats. When those ducts get damaged, bile backs up, causing inflammation, scarring, and eventually cirrhosis. It mostly affects women between 30 and 65. The exact cause isn’t known, but genetics play a role-certain gene variants like HLA-DR8 and IL12A increase risk. Environmental triggers, like certain bacterial infections (E. coli in urinary tract infections), may also kickstart the process.
Many people don’t feel symptoms at first. Fatigue and itchy skin (pruritus) are the most common early signs. By the time jaundice or abdominal pain shows up, the disease is often advanced. That’s why blood tests are critical. Elevated alkaline phosphatase (ALP) is the key marker doctors look for. Anti-mitochondrial antibodies (AMAs) are found in 95% of PBC patients and help confirm the diagnosis.
UDCA: The Foundation of Treatment for Over 30 Years
Ursodeoxycholic acid (UDCA) has been the go-to treatment since the 1990s. It’s a naturally occurring bile acid, taken as a pill once or twice daily at a dose of 13-15 mg per kilogram of body weight. It works by replacing toxic bile acids with gentler ones, helping bile flow better and reducing liver inflammation.
It’s not perfect. About 35% of patients don’t respond well-meaning their ALP stays above 1.67 times the upper limit of normal after a full year of treatment. That’s the benchmark doctors use to decide if the drug is working. For those who do respond, the results are strong: 87% survive without needing a liver transplant after 10 years. For non-responders? That number drops to 69%. So, if UDCA isn’t working, the risk of liver failure climbs.
The Big Shift: Why Obeticholic Acid Was Withdrawn
For nearly a decade, obeticholic acid (Ocaliva) was the only other approved option after UDCA failed. It worked by activating the FXR receptor, which helped regulate bile production. In clinical trials, it improved ALP levels better than placebo. But real-world data told a different story.
By 2024, safety concerns piled up. Severe itching affected 56% of users. More worrying: a 2024 FDA analysis showed a higher rate of serious heart problems and death in patients with advanced liver disease. In September 2025, the FDA officially pulled Ocaliva off the market. The advisory committee voted 12 to 3 against keeping it, citing that the risks outweighed the benefits-especially for patients already with cirrhosis or severe itching.
This wasn’t just a drug recall. It was a wake-up call. Doctors had to go back to the drawing board. Suddenly, thousands of patients on OCA needed new treatment plans. And the two new drugs-seladelpar and elafibranor-were thrust into the spotlight.
Seladelpar (Livdelzi): The New Front-Runner
Seladelpar, sold as Livdelzi, was approved by the FDA in December 2024. It works by targeting 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 only 20% on placebo. Even more impressive: 42% achieved ALP normalization-meaning their levels dropped below 1.5 times the upper limit of normal.
It’s not just about lab numbers. Itching, the most frustrating symptom for PBC patients, improved by 45% on seladelpar versus 15% on placebo. That’s life-changing. In real-world data from 396 patients, 85% stayed on the drug after one year. That’s a high retention rate, especially compared to OCA, where 38% stopped due to side effects.
There’s a catch. About 25% of patients experience worse itching in the first two weeks. That’s why doctors start at 5 mg daily and slowly increase to 10 mg after four weeks. For most, the itching fades by week 8. The key is patience and close monitoring. If you’re switching from OCA, many report feeling better within 8 weeks.
Elafibranor (Iqirvo): A Strong Alternative
Elafibranor, branded as Iqirvo, got FDA approval in November 2024. It’s a dual PPAR-alpha/delta agonist, meaning it works on two targets at once. In the ELATIVE trial, 56% of patients achieved a composite biochemical response (ALP reduction plus normal bilirubin), compared to just 12% on placebo. ALP normalization hit 21%-solid, but not quite as high as seladelpar.
Itching improved by 38%, which is still meaningful. One advantage? No dose titration needed. You take 80 mg once daily from day one. It also helps with cholesterol and triglycerides, lowering them by 24%-a bonus for patients with metabolic syndrome or fatty liver.
But it’s not without risks. About 18% of patients saw a rise in creatinine, a marker of kidney function. That doesn’t mean kidney damage, but it does mean doctors need to monitor kidney health more closely. It’s a good option for people who can’t tolerate the initial itching spike with seladelpar, or who need help with lipid control.
How Doctors Decide: Treatment Sequencing in 2025
Today’s treatment plan is clear-cut:
- Start with UDCA. All newly diagnosed patients begin here. No exceptions.
- Test response at 12 months. If ALP is still above 1.67x ULN, you’re a non-responder. Time to move to second-line.
- Second-line: Seladelpar first. Because of its superior ALP normalization and itching relief, it’s now the preferred second-line option according to updated AASLD guidelines.
- Then elafibranor. If seladelpar doesn’t work, causes intolerable side effects, or isn’t covered by insurance, elafibranor is next.
- Fibrates (off-label). Drugs like fenofibrate are sometimes used if the above don’t work or aren’t available. They’re cheaper and have some evidence of benefit, but aren’t officially approved for PBC.
Monitoring is key. ALP is checked every 3 months during dose changes, then every 6 months once stable. A single high reading doesn’t mean failure. What matters is the trend over time. A sustained 15% drop-even without full normalization-is still linked to better survival.
What About Cost and Access?
Seladelpar and elafibranor are expensive. In the U.S., out-of-pocket costs can exceed $500 a month for many patients, even with insurance. Medicare requires proof of UDCA failure and ALP >1.67x ULN before covering them. Denial rates for prior authorization are around 28% for seladelpar.
Community clinics are slower to adopt these drugs than academic centers. About 82% of university hospitals have updated their protocols, but only 63% of private practices have. That means where you get care can affect your access. Patient advocacy groups like the PBC Foundation now offer free “Treatment Navigator” tools to help patients understand their options and appeal insurance denials.
What’s Next? The Pipeline and Future of PBC Care
The research hasn’t stopped. Twelve new drugs are in development. Setanaxib, which targets oxidative stress, is in Phase 3 and could be available by 2027. Cenicriviroc, which reduces liver inflammation, and lupinatuzumab, an immune-targeting antibody, are also moving forward.
One of the most exciting areas is the gut-liver connection. VE-202, a fecal microbiota transplant in capsule form, is in Phase 2 trials. Early results suggest altering gut bacteria may calm the autoimmune response in PBC. If it works, it could open a whole new treatment path.
The FDA is also changing how it measures success. In 2025, it accepted the PBC-40 PRO-a patient-reported outcome tool-as a valid endpoint in clinical trials. That means future drugs won’t just be judged by ALP numbers. How you feel-your energy, your sleep, your itching-will matter just as much.
Real Talk: What Patients Are Saying
In a survey of 1,247 PBC patients by MyPBCteam in August 2025, 68% of those who switched from OCA to seladelpar said their quality of life improved within two months. But 22% said their itching got worse before it got better. That’s normal. It’s not a sign the drug isn’t working-it’s part of the adjustment.
One patient in Seattle, 52, shared: “I was on OCA for three years. I couldn’t sleep because of the itching. I lost 15 pounds because I didn’t want to eat. After switching to seladelpar, I slept through the night for the first time in years. The itching didn’t vanish, but it went from ‘can’t live like this’ to ‘manageable.’”
Another in Toronto, 68, switched to elafibranor after seladelpar caused stomach issues. “I didn’t have the itching spike. My ALP dropped. My triglycerides improved. My doctor said I’m now in the best shape I’ve been in since diagnosis.”
These aren’t isolated stories. They’re the new reality of PBC care in 2025.
Final Thoughts: Hope, But Not a Cure
PBC is still a chronic disease. There’s no cure. But the goal isn’t to eliminate it-it’s to stop it from destroying your liver. With UDCA, seladelpar, and elafibranor, most patients can now control the disease for decades. The key is early diagnosis, consistent monitoring, and not giving up if the first treatment doesn’t work.
The withdrawal of OCA was a setback, but it forced the field to find better, safer options. Seladelpar and elafibranor aren’t perfect. But they’re real progress. And with more drugs on the horizon, the future for PBC patients has never looked brighter.