Primary Biliary Cholangitis Treatment: What Works in 2026

Primary Biliary Cholangitis (PBC) isn’t just another liver condition. It’s a slow-burning autoimmune disease where your immune system attacks the tiny bile ducts inside your liver. Over time, this leads to bile buildup, scarring, and eventually cirrhosis. It mostly affects women between 30 and 65, and while it’s rare-about 1 in 4,000 people have it-it’s becoming easier to manage than ever before. The big change? The treatment landscape shifted dramatically in late 2025 after obeticholic acid (Ocaliva) was pulled from the market. Now, doctors have clearer, safer options to help patients live longer, feel better, and avoid liver transplants.

What Is Primary Biliary Cholangitis?

PBC is an autoimmune disease, meaning your body’s defense system turns against itself. Specifically, it targets the bile ducts in your liver. Bile is supposed to carry waste out of your liver, but when those ducts get damaged, bile backs up and poisons liver cells. The root cause? Your immune system mistakenly attacks a protein called PDC-E2, found in the mitochondria of bile duct cells. No one knows exactly why this happens, but genetics play a role-people with HLA-DR8, IL12A, or STAT4 gene variants are more at risk. Environmental triggers like urinary tract infections (especially from E. coli) may also spark the process.

Early symptoms are often mild: fatigue, itchy skin, dry eyes or mouth. Many people are diagnosed only after routine blood tests show high levels of alkaline phosphatase (ALP), a liver enzyme that spikes when bile flow is blocked. Left untreated, PBC can lead to cirrhosis, liver failure, and the need for a transplant. But with the right treatment, most people live decades without major complications.

First-Line Treatment: Ursodeoxycholic Acid (UDCA)

For over 30 years, ursodeoxycholic acid (UDCA), also called ursodiol, has been the gold standard for PBC. It’s cheap, well-studied, and taken as a daily pill-usually 13 to 15 mg per kilogram of body weight. So if you weigh 70 kg, that’s about 900-1,050 mg per day.

UDCA works by replacing toxic bile acids with ones your liver can handle. It also reduces inflammation and helps move bile out of the liver. The results? About 60-65% of patients respond well. That means their ALP levels drop significantly, and their 10-year survival without needing a transplant jumps to 87%. For non-responders, that number drops to 69%.

But here’s the catch: 35% of patients don’t respond enough. That’s where things get tricky. If your ALP stays above 1.67 times the upper limit of normal after 12 months of UDCA, you’re considered a non-responder. And until recently, there weren’t many good options after that.

The Old Second-Line Drug: Why Ocaliva Was Withdrawn

For nearly a decade, obeticholic acid (Ocaliva) was the go-to second-line treatment. Approved in 2016, it worked by activating the farnesoid X receptor (FXR), which helps regulate bile acid production. In clinical trials, it lowered ALP better than placebo-46% of patients reached target levels versus 10% on placebo.

But the side effects were serious. Over half of patients had severe itching, and 5% stopped taking it because of it. Worse, long-term data showed increased risk of liver-related death in patients with advanced scarring. A 2024 FDA safety review found an 8.9% rate of serious heart problems in OCA users versus 5.2% on placebo. By September 2025, the FDA pulled it from the market after the Gastrointestinal Drugs Advisory Committee voted 12-3 against keeping it available. The message was clear: the risks outweighed the benefits.

New Second-Line Options: Seladelpar and Elafibranor

With Ocaliva gone, two new drugs stepped in-both approved in late 2024 and now standard in 2026.

Seladelpar (Livdelzi) is a selective PPAR-δ agonist made by Gilead. It’s taken as a 5 mg tablet daily, with a possible increase to 10 mg after four weeks. In the Phase 3 RESPONSE trial, 70% of patients saw ALP drop by at least 15% compared to only 20% on placebo. Even more impressive: 42% achieved ALP normalization (below 1.5x ULN), versus just 6% on placebo. It also cuts itching by 45%-a huge win for patients who suffer daily from this symptom. Real-world data from 396 patients shows 85% stayed on seladelpar after one year, compared to only 62% on OCA.

The downside? About 25% of patients get worse itching in the first two weeks. But in 92% of those cases, it fades by week 8. That’s why doctors start low and go slow.

Elafibranor (Iqirvo), made by Genfit, is a dual PPAR-α/δ agonist. It’s simpler: 80 mg once daily, no titration needed. In the ELATIVE trial, 56% of patients hit the composite response (ALP drop + normal bilirubin), versus 12% on placebo. ALP normalization hit 21%, and itching improved by 38%. It also lowers triglycerides by 24%, which helps patients with metabolic syndrome or fatty liver.

But elafibranor raises creatinine in about 18% of users. That doesn’t mean kidney damage-it’s a marker that needs monitoring. Your doctor will check your kidney function every 3 months.

Comparing the New Drugs

Here’s how seladelpar and elafibranor stack up:

So which one is better? For most patients with severe itching, seladelpar is preferred. For those with high triglycerides or metabolic issues, elafibranor may be a better fit. Both are far safer than Ocaliva was.

What About Fibrates?

Fibrates-like fenofibrate or bezafibrate-are older cholesterol-lowering drugs. They’re not FDA-approved for PBC, but many doctors use them off-label, especially if patients can’t access seladelpar or elafibranor due to cost or insurance. Studies show they can lower ALP by 20-30% and improve itching in about half of patients. They’re cheap and widely available, but they’re not as powerful as the newer drugs. They’re often used as a bridge or add-on, not a replacement.

Monitoring and Treatment Goals

There’s no one-size-fits-all goal. But here’s what experts agree on:

• Check ALP every 3 months during the first year of treatment, then every 6 months.
• Response is defined as ALP dropping below 1.67x ULN after 12 months of UDCA.
• Full normalization (ALP <1.5x ULN) is ideal-but even a 40% reduction improves survival.
• Each 10% drop in ALP reduces your risk of transplant or death by 7.2%.

Doctors now focus on trends, not single numbers. A steady decline over six months matters more than one low reading. And if you’re feeling better-less itching, more energy-that’s just as important as lab values.

What’s Coming Next?

The pipeline is full. Twelve new drugs are in development, including:

• Setanaxib (NOX1/4 inhibitor)-Phase 3 results expected in 2026.
• Tropifexor (FXR agonist)-Phase 2b, avoids the side effects of Ocaliva.
• Lanifibranor (pan-PPAR agonist)-could combine benefits of seladelpar and elafibranor.
• VE-202 (fecal microbiota capsule)-targets gut-liver axis, Phase 2 results in mid-2026.

There’s also growing interest in patient-reported outcomes. The FDA recently approved the PBC-40 PRO tool as a way to measure quality of life in clinical trials. That means future treatments won’t just be judged by blood tests-but by how patients actually feel.

Access and Cost Challenges

Even with better drugs, access is uneven. Seladelpar and elafibranor cost over $500 per month out-of-pocket for many patients. Medicare requires proof of UDCA failure and ALP >1.67x ULN before covering them. About 28% of prior authorizations for seladelpar get denied. Community clinics lag behind academic centers-only 63% have adopted the new guidelines versus 82% at major hospitals.

Patients are turning to resources like the PBC Foundation’s Treatment Navigator and AASLD’s mobile app to understand their options. If you’re struggling with cost, ask your doctor about patient assistance programs. Both Gilead and Genfit offer co-pay cards and free drug programs for qualifying patients.

Final Thoughts: Hope Is Real

PBC used to feel like a death sentence. Now, it’s a manageable chronic condition. UDCA still works for most. For those who need more, seladelpar and elafibranor offer real hope-better labs, less itching, longer life. The withdrawal of Ocaliva wasn’t a setback; it was a correction. The new drugs are safer, more targeted, and backed by stronger data.

The key is early diagnosis and regular monitoring. If you’ve been diagnosed with PBC, don’t wait. Talk to your doctor about your ALP levels, your symptoms, and your treatment options. You’re not stuck with outdated care. The future of PBC treatment is here-and it’s working.