Researchers have learned a lot lately about primary biliary cholangitis (PBC), a chronic liver disease that affects the bile ducts. PBC is an autoimmune disease, which means the immune system mistakenly attacks the body’s own tissues. Their findings help explain why improved blood test results don’t always mean you’ll feel better and may offer clues to the future of PBC treatment.

There’s no cure for PBC, but researchers worldwide are studying this disease to learn more about the best way to treat it. For years, the goal of treating PBC was pretty straightforward: lower the numbers that tell us when there’s ongoing liver damage.

Now, researchers are asking bigger questions. This article reviews the latest research on PBC and how it may affect future PBC treatments. 

For many years, ursodiol (Urso 250), also called ursodeoxycholic acid (UDCA), was the main treatment for PBC. Obeticholic acid (Ocaliva) later became another FDA-approved option, but its U.S. approval was withdrawn in 2025 after safety concerns and questions about its clinical benefit. Ursodiol remains the first-line treatment for PBC.

For people who don’t respond to ursodiol or whose disease continues to progress — leading to fibrosis (scarring of the liver) or liver failure — researchers have been working to identify new treatment options.

Peroxisome Proliferator-Activated Receptor Agonists

One important advance in PBC treatment is a new group of medications called peroxisome proliferator-activated receptor (PPAR) agonists. These drugs help the body regulate bile acids and reduce liver inflammation. They can improve liver blood test results, but researchers are still studying whether they reduce serious liver complications over time.

In 2024, the FDA approved elafibranor (Iqirvo) and seladelpar (Livdelzi) for the treatment of PBC in people with an inadequate response or intolerance to ursodiol. Both medicines received accelerated approval based on improvements in liver blood tests. Researchers are still studying whether these improvements lead to fewer serious liver complications, a reduced need for liver transplant, or longer survival.

In a large clinical trial called ELATIVE, 51 percent of people taking elafibranor met the study’s blood test goals after one year, compared with 4 percent of those taking a placebo. Alkaline phosphatase (ALP) levels returned to the normal range in 15 percent of people taking elafibranor.

Similar results were found with seladelpar. In the phase 3 RESPONSE trial, about 61 percent of people taking seladelpar met the study goals at one year, compared with 20 percent receiving placebo. ALP levels decreased to normal levels in 25 percent of those taking seladelpar.

While these results are promising, improving ALP and total bilirubin levels isn’t the only goal of treatment. For people living with PBC, treatment success should also include improving symptoms and quality of life.

Many people with PBC don’t have any symptoms when they’re first diagnosed. Symptoms such as pruritus (itchy skin) and fatigue can occur at different stages of PBC. Researchers have started to look at both biochemical response and symptom reduction as goals of treatment.

Seladelpar stands out for reducing disease markers and pruritus compared to placebo. Elafibranor reduced disease markers, but itching was not significantly reduced compared to placebo. These findings show that improving PBC disease markers doesn’t necessarily relieve symptoms.

ALP and total bilirubin are important markers for PBC outcomes. Recent research suggests noninvasive tests can provide useful information alongside blood test results. Together, these results may give your doctor a clearer picture of how likely your PBC is to progress.

These new approaches include:

• Liver stiffness measurement — Using transient elastography (FibroScan) to monitor liver stiffness can assess disease progression over time
• Fibrosis risk scores — Use a mix of blood test results and other health information to estimate liver scarring

Recent research suggests that liver stiffness may help identify higher-risk people with PBC even if they appear to have favorable risk scores. A 2025 study found that people with PBC who had low-risk scores but elevated liver stiffness had a higher rate of disease progression than those with lower liver stiffness.

Two people with PBC can have similar ALP and total bilirubin levels but different risks of disease progression. Researchers are refining treatment targets to support a more individualized approach to care.

Researchers are now looking at whether deeper biochemical responses can provide greater protection against disease progression in PBC. Some clinical trials have defined biochemical response as an ALP level that decreases by at least 15 percent and remains below a set cutoff, along with bilirubin within the normal range.

Researchers are now looking at whether barely meeting a response threshold, particularly for ALP, offers the same benefit as achieving a deeper biochemical response, such as normal ALP levels.

Recent studies of seladelpar and elafibranor have increased interest in ALP normalization as a potential treatment goal, rather than focusing only on whether ALP falls below a response threshold.

Large international studies have found that people with normal ALP levels had a lower risk of PBC complications, such as liver failure. Bilirubin also remains an important marker of long-term risk. In general, people with lower or normal bilirubin levels tend to have better outcomes, especially when ALP is also well controlled.

Researchers are looking beyond whether treatment works and asking how much blood test results improve, including whether ALP levels return to normal.

Pruritus due to PBC can be difficult to treat. Newer medicines are changing how PBC-related pruritus is treated. Some are now approved, while others are still being studied.

Linerixibat

Linerixibat (Lynavoy) was FDA-approved in March 2026 to treat cholestatic itching caused by PBC in adults. It works by blocking the reabsorption of bile acids in the intestine, which helps reduce itching. While linerixibat is used to treat PBC-related itching rather than the underlying liver disease, it can help reduce this symptom.

Volixibat

Volixibat, another IBAT inhibitor, is still being studied in the VANTAGE trial. Early results suggest it may reduce PBC-related itching, but more research is needed to confirm how well it works and whether it affects the course of the disease.

TH104

Another medication in the treatment pipeline is TH104, which is being studied for moderate to severe PBC-related itching. Research is still ongoing to determine its safety, tolerability, and effects on PBC.

As our understanding of PBC continues to grow, researchers are also exploring new treatments that target pathways involved in inflammation, cholestasis, and liver injury.

Setanaxib

Setanaxib is a new treatment being studied for PBC. It targets processes that can cause liver damage and scarring. In the phase 2b TRANSFORM study, setanaxib reduced ALP levels, a blood marker used to track PBC. Researchers still need to determine whether the drug can slow liver scarring or long-term disease progression.

While the results are encouraging, more studies are needed to see if setanaxib can slow down liver fibrosis and remain safe over time. Other treatments targeting PPAR pathways also continue to be studied.

Pemafibrate

Pemafibrate is a PPAR modulator that has been shown to reduce ALP levels and improve risk scores. More research is needed, and it remains investigational for PBC in the United States.

Saroglitazar

Saroglitazar is another PPAR-targeted therapy currently being studied. Saroglitazar has been shown to reduce ALP levels within four weeks of starting treatment. However, more research is needed to see if it can improve long-term clinical outcomes.

Researchers hope these investigational treatments can improve blood test results and symptoms while also slowing disease progression and reducing long-term complications.

Researchers still need to learn whether newer therapies for PBC can lead to better long-term health outcomes. Improving liver blood tests is promising, but researchers still need to learn whether newer treatments slow the disease enough to reduce serious complications over time.

PBC can progress slowly, so studies that follow people for years are needed to understand long-term health outcomes.

This information can help healthcare providers understand which treatments provide long-term benefits and how they may improve outcomes for people with PBC.

Read more about PBC treatment options ❯