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Primary biliary cholangitis (PBC) is a liver disease that affects the bile ducts in your liver. It’s a chronic (long-term) condition that can worsen over time, causing serious problems, such as cirrhosis (advanced liver scarring) and liver cancer. There’s no cure for PBC, but researchers worldwide are studying this disease to learn more about the best way to treat it.
This article will review the latest research on PBC and how it may affect future PBC treatments.
Scientists still don’t fully understand what causes some people to develop PBC. It’s thought that a combination of genetic and environmental factors may cause an autoimmune reaction — when your immune system mistakenly attacks your own healthy tissues. Research continues to reveal new information about what may trigger PBC and how PBC can affect your liver.
A study from 2024 found a protein called E-cadherin that might be linked to damage in the bile ducts of people with PBC. Normally, E-cadherin helps protect the cells in the bile ducts. But in people with PBC, a type of white blood cell called CD8-positive T cells had more E-cadherin. This made it easier for them to go to the bile ducts and cause inflammation. This could be one reason why the bile ducts get damaged. In the future, doctors might target this protein to help treat PBC.
A genome-wide association study is a research approach that looks across the entire genome — the full set of a person’s DNA — to find genetic differences linked to specific diseases. As of 2022, these types of studies have found about 70 genes associated with PBC. These insights may help healthcare providers identify people at risk for PBC.
Researchers have also been looking into environmental triggers associated with PBC. A 2022 study from Japan found that growing up in an environment with poor hygiene and being exposed long term to chemicals in cigarettes and hair dye were linked to a higher risk of developing PBC.
Early PBC diagnosis is associated with a better prognosis (outcome) because treatment can begin sooner. PBC is usually diagnosed with antibody tests. These tests check for specific autoantibodies — immune proteins that target healthy tissue. Most people with PBC have a specific type of autoantibody called antimitochondrial antibodies.
Researchers are currently searching for other PBC-specific autoantibodies that may help with diagnosis and predicting outcomes. For example, autoantibodies called anti-gp210 and anti-Sp100 may help predict outcomes in people with PBC.
In the past, there were only two medications approved by the U.S. Food and Drug Administration (FDA) to treat PBC: ursodiol (ursodeoxycholic acid, or UDCA) and obeticholic acid (Ocaliva).
In September 2025, however, the manufacturer withdrew Ocaliva, following a request from the FDA. The agency had raised safety concerns about the drug and questions about its long-term effectiveness.
Research into how PBC develops and affects the body has led to recent FDA-approved medications that offer new treatment options for people with PBC.
Peroxisome proliferator-activated receptor (PPAR) agonists are the newest class of medications approved to treat PBC. Researchers don’t fully understand how these drugs work. It’s thought that they stimulate the PPAR protein to regulate how lipids (fats) and bile acids are broken down.
Two PPAR agonists — elafibranor (Iqirvo) and seladelpar (Livdelzi) — received accelerated FDA approval in 2024. These medications offer a treatment option for people who don’t respond well or cannot tolerate UDCA. Their approval was based on improvements in laboratory markers linked to liver function, including alkaline phosphatase (ALP). Additionally, seladelpar was shown to improve pruritus (itching).
Continued approval depends on ongoing research to see if there’s a positive effect on long-term outcomes, like survival or avoiding liver transplants.
Clinical trials are ongoing for other PPAR agonists, including saroglitazar and pemafibrate, which are not yet FDA-approved.
PPAR agonists aren’t the only new type of PBC treatment researchers are studying. Several types of medications are being studied in clinical trials to see how well they work for people with PBC. Some new medications may help slow disease progression, while others are focused on improving PBC symptoms and quality of life.
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors, also known as NOX inhibitors, may help improve liver fibrosis (scarring). NADPH oxidase is a protein involved in the development of liver fibrosis by producing reactive oxygen species (ROS), which are linked to liver scarring. It’s thought that by blocking the NOX protein, NOX inhibitors may improve fibrosis.
Setanaxib is a NOX inhibitor that researchers are currently studying for PBC. Early results of clinical trials found that setanaxib significantly lowered ALP levels in people with early-stage liver scarring (measured by liver stiffness). However, more people stopped this treatment due to side effects compared to the placebo (inactive treatment) group. In the future, larger studies are needed to learn more about the safety and tolerability of setanaxib.
Non-bile acid farnesoid X-receptor (FXR) agonists are a new type of medication being studied for various liver diseases, including PBC. Bile acids normally activate the FXR protein to help regulate how the liver makes and transports bile acids, as well as the breakdown of fats and carbohydrates. Obeticholic acid works by activating FXR and is known as a bile acid FXR agonist.
Tropifexor is a non-bile acid FXR agonist designed to activate FXR. Early clinical trials suggest that this drug may help improve signs of bile duct damage in people with PBC.
Ileal bile acid transport (IBAT) inhibitors are a class of medications that may help improve itching in people with PBC. These medications work by decreasing how much bile acid is absorbed by your small intestines. The primary treatment for PBC, UDCA, isn’t very effective at controlling itching for most people.
There aren’t any IBAT inhibitors currently FDA-approved for PBC-related itching. However, linerixibat and volixibat are two IBAT inhibitors that are being studied in clinical trials. In a 24-week phase 3 clinical trial, more people taking linerixibat experienced improvements in itching and sleep compared to those taking the placebo. Early clinical trials for volixibat have also shown improvement in itching.
CNP-104 is a new investigational therapy that takes a different approach from other PBC treatments. It’s a biodegradable nanoparticle designed to retrain the immune system by targeting agents that drive inflammation in PBC. Results from early clinical trials found reduced immune activity against the bile ducts and less progression of liver stiffness compared to the placebo. Larger studies are planned to learn more about the safety and efficacy of this new treatment.
New treatments for PBC have made it possible for healthcare providers to push for more aggressive treatment goals, which may help improve PBC outcomes.
Due to the slow progression of PBC, healthcare providers often monitor levels of substances in the blood — like ALP and bilirubin — to check how well treatment is working. Lower levels are usually linked to better long-term health outcomes.
Doctors often compare your lab results to something called the “upper limit of normal” (ULN) — the highest level considered typical in a healthy person. In clinical trials, an ALP level below 1.67 times the ULN and a bilirubin level within the normal range are commonly used as markers to help predict a person’s risk of serious complications from PBC, including the potential need for a liver transplant.
New medications, such as PPAR agonists, may increase the chance of reaching normal levels of ALP and bilirubin. Although reaching a normal level of ALP or bilirubin is considered a positive sign in research, it’s not yet fully proven that this will lead to better outcomes or survival for people with PBC. New drugs that improve these laboratory markers still need more data to confirm long-term benefits.
An article in the journal Digestive Diseases and Sciences found that 50 percent to 70 percent of people with PBC experience itching. Even though this symptom can greatly affect quality of life, it’s often undertreated. Some treatments can actually worsen PBC symptoms, including itching.
With the approval of newer effective PBC treatments, such as IBAT inhibitors, healthcare providers may be able to prioritize treatments that improve itching. Additionally, NOX inhibitors, like setanaxib, may help improve fatigue, another PBC symptom that’s often hard to treat.
Clinical trials help researchers discover more about PBC and the most effective treatments. Several clinical trials are currently ongoing to reveal more about the safety and efficacy of new and established treatments for PBC. If you’re interested in joining a clinical trial for PBC, talk to your healthcare provider to see if you qualify for any in your area.
On myPBCteam, people share their experiences with primary biliary cholangitis, get advice, and find support from others who understand.
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