For decades, treating primary biliary cholangitis (PBC) largely meant prescribing one medication and watching liver tests. Ursodiol changed the outlook for many people with PBC, and it’s still the foundation of treatment. However, it became clear that one drug couldn’t adequately control the disease for everyone. 

That realization reshaped PBC care. Doctors now have better ways to identify people at higher risk of disease progression, clearer targets for judging whether treatment is working, and more medications to consider when ursodiol isn’t enough. 

Although ursodiol hasn’t gone anywhere, PBC treatment has shifted from a mostly one-size-fits-all approach toward a more individualized question: Is this treatment controlling this person’s disease well enough? 

‘On Treatment’ May Not Mean ‘Controlled Disease’

One of the biggest changes in PBC care involves recognizing the importance of biochemical response, or how well treatment improves liver blood test results. Some people treated with UDCA don’t have an adequate response and continue to face a greater risk of the disease getting worse.

It’s no longer enough to just prescribe UDCA. Healthcare providers also need to determine whether it’s working well enough. Several factors help answer that question:

• Alkaline phosphatase (ALP) — ALP levels that stay high over time are linked to a greater long-term risk of PBC getting worse.
• Bilirubin — Rising bilirubin levels can signal a higher risk of disease progression.
• Treatment response — Guidelines have traditionally recommended assessing response to UDCA after about 12 months.
• Disease stage — Fibrosis, cirrhosis, and portal hypertension (high blood pressure in the vein that carries blood to the liver) can affect outlook and treatment decisions.
• Risk scores — The GLOBE and UK-PBC scores combine clinical information and blood test results to estimate longer-term risk.

Healthcare providers have shifted from asking only whether a person is taking UDCA to assessing how much risk remains despite treatment and what more can be done.

Obeticholic Acid Expanded Treatment but Was Withdrawn

For years, healthcare providers had few approved alternatives when UDCA wasn’t enough. That changed in 2016, when the U.S. Food and Drug Administration (FDA) approved obeticholic acid (OCA) for adults whose PBC didn’t respond well enough to UDCA or who couldn’t tolerate UDCA. The approval was based on OCA’s ability to lower ALP.

OCA, a farnesoid X receptor agonist, improved blood test signs of PBC activity. Its arrival was a milestone because it provided an FDA-approved second-line treatment option for PBC.

However, OCA also demonstrated why disease stage and safety matter. In 2021, the FDA restricted its use because of the risk of serious liver injury in people with advanced cirrhosis.

The story ultimately changed again. OCA was withdrawn from the U.S. market in 2025 and is no longer available as a PBC treatment in the United States. That’s important to know when reading older resources that may still list it as a second-line option.

2024 Brought a New Generation of Treatment Options

Drugs that target peroxisome proliferator-activated receptors (PPARs), which are involved in processes including bile acid metabolism and inflammation, have long been studied for PBC. In 2024, two PPAR-targeting therapies became the first in this group to receive FDA approval for PBC in the United States.

Elafibranor

The FDA granted accelerated approval to elafibranor (Iqirvo) in June 2024. Accelerated approval allows the FDA to approve certain drugs based on a measure thought to predict clinical benefit while studies continue to confirm that benefit.

Elafibranor is a PPAR agonist that can be used with UDCA in adults who have an inadequate response or alone in adults who can’t tolerate UDCA. The phase 3 ELATIVE trial showed a substantially greater biochemical response with elafibranor than with a placebo.

Seladelpar

The FDA granted accelerated approval to seladelpar (Livdelzi) in August 2024 for a similar group of adults. The phase 3 RESPONSE trial found a significantly greater biochemical response with seladelpar than with a placebo. It also improved pruritus (itching) among participants who had moderate to severe itching at the start of the study.

These drugs didn’t replace UDCA. They expanded what healthcare providers can do when UDCA alone isn’t controlling PBC well enough.

Fibrates

Fibrates, including bezafibrate and fenofibrate, have also played a role in treating PBC. Studies show that adding a fibrate to UDCA can improve liver blood test results after an inadequate response to UDCA.

Bezafibrate is used for PBC in some countries. In the United States, bezafibrate is not available, and fenofibrate has been used off-label, meaning the FDA hasn’t specifically approved it for this condition.

Treatment Is a Pathway Rather Than a Single Prescription

Modern PBC care is increasingly built around treatment, reassessment, and adjustment:

• Start with UDCA. It remains the standard first-line disease-modifying treatment.
• Check how treatment is working. Healthcare providers follow liver tests, especially ALP and bilirubin, along with disease stage and symptoms.
• Assess the risk of worsening disease. Response criteria and tools such as GLOBE and UK-PBC help identify people at greater risk of PBC progression.
• Add or change therapy when needed. In the United States, elafibranor and seladelpar are options for certain adults who have an inadequate response to UDCA or can’t tolerate it.
• Keep reassessing. Treatment may change as liver blood tests, symptoms, disease stage, medication tolerance, or other health conditions change.

There’s also growing interest in aiming for deeper improvement in liver blood tests. Clinical trials have commonly used an ALP around or below 1.67 times the upper limit of normal, along with normal bilirubin, as part of the definition of treatment response.

Increasing evidence suggests that lower ALP and bilirubin levels, including ALP returning to normal, may be linked to better long-term outcomes. The goal is increasingly becoming not just some improvement, but the best disease control that can be safely achieved.

Treating PBC and Treating Its Symptoms Are 2 Different Jobs

Controlling the disease itself doesn’t necessarily mean a person will feel better with PBC.

Two difficult PBC symptoms are itching and fatigue. They don’t always correspond with liver disease severity, so symptoms often need their own treatment plan. For itching, options can include:

• Cholestyramine, traditionally used as a first-line therapy
• Linerixibat (Lynavoy), an FDA-approved medication for adults with itching caused by PBC
• Rifampin when itching persists
• Opioid antagonists, such as naltrexone, for some people
• Sertraline, which may help some people with itching that doesn’t go away

These drugs primarily manage symptoms. They shouldn’t be confused with medications intended to slow PBC progression.

There can be overlap. Seladelpar is noteworthy because clinical trial data showed improvement in both liver blood tests and itching in certain people.

Fatigue remains harder to treat. There’s no established treatment specifically for PBC-related fatigue. Healthcare providers may instead look for contributors such as:

• Anemia or thyroid disease
• Sleep disorders
• Depression
• Medication effects

The distinction between disease control and helping people feel better day to day is now an important part of comprehensive PBC care.

Where Does PBC Treatment Go From Here?

PBC treatment has come a long way from the era when UDCA was essentially the only approved treatment aimed at slowing the disease itself.

Elafibranor and seladelpar received accelerated approval based on improvements in liver blood tests that are thought to predict clinical benefit. Longer-term studies are underway to confirm how these treatments affect outcomes such as liver decompensation (when severe liver damage leads to serious health problems), liver transplant, and survival. Other priorities include:

• Finding better treatments for persistent fatigue and itching that don’t improve enough with current options
• Determining how early additional therapy should begin
• Better matching therapies to individuals
• Understanding whether combination treatment can provide better disease control
• Developing treatments that address the immune system problems driving PBC

In 2026, the FDA approved linerixibat (Lynavoy) specifically for cholestatic itching caused by PBC in adults. This gives people with PBC another treatment option for itching, although more effective treatments are still needed for people whose symptoms remain difficult to control.

Liver transplant also remains essential for people who progress to very advanced liver disease or develop serious health problems despite treatment.

The biggest change over the past 30 years isn’t just that PBC has more treatment options. Healthcare providers have also become better at recognizing that different people face different risks and may need different treatment strategies.

UDCA remains the foundation. What’s changed is what can happen next.

Read more about PBC treatment options ❯