Primary biliary cholangitis (PBC) is a liver disease that affects the bile ducts in your liver. It’s a 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.

Research on the Causes of PBC

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 2024 study identified a protein called E-cadherin that may be associated with damage to the bile ducts in people with PBC. Normally, E-cadherin helps protect bile duct cells. In those with PBC, researchers found that certain inflammatory white blood cells, called CD8+ T cells, had higher levels of E-cadherin. This protein made it easier for these cells to travel to the bile ducts. These findings suggest that E-cadherin may play a key role in bile duct damage in people with PBC. In the future, this protein may be used as a target for PBC treatments.

A genome-wide association study (GWAS) 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, GWASs have found about 70 genes associated with PBC. A greater understanding of the genes involved in developing PBC may help health care providers identify people at risk for the disease.

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.

Research on Diagnosis and Prognosis of PBC

Early PBC diagnosis is associated with a better prognosis (outcome) because treatment can begin sooner. To diagnose PBC, health care providers use antibody tests. These tests check for specific autoantibodies — immune proteins that target your own healthy tissue. Most people with PBC have a specific type of autoantibody called antimitochondrial antibodies.

Another type of antibody, PBC-specific antinuclear antibodies such as anti-gp210 and anti-sp100, can help predict outcomes in people with PBC. Researchers are currently searching for other autoantibodies in people with PBC that may help with diagnosis and predicting outcomes.

New PBC Treatments

In the past, there were only two medications approved by the U.S. Food and Drug Administration (FDA) to treat PBC — ursodeoxycholic acid (Ursodiol) and obeticholic acid (Ocaliva). 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 Agonists

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.

Currently, there are two FDA-approved PPAR agonists. Elafibranor (Iqirvo) was approved in June 2024, and seladelpar (Livdelzi) was approved in August 2024. Clinical trials have shown that these medications can improve certain markers of PBC, like levels of alkaline phosphatase (ALP), an enzyme linked to liver function. Additionally, seladelpar was shown to improve pruritus (itching).

These medications offer a treatment option for people who don’t respond well to ursodeoxycholic acid. However, because they are newer drugs, researchers still need to learn more about how well these medications work over the long term.

Clinical trials are ongoing for other PPAR agonists, including saroglitazar and pemafibrate.

Future Potential PBC Treatments

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.

NOX Inhibitors

Nicotinamide adenine dinucleotide phosphate hydrogen (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. If inflammation continues, more scar tissue will form. This scarring can eventually lead to cirrhosis or liver failure. It’s thought that by blocking the NOX protein, NOX inhibitors may improve fibrosis.

Setanaxib is a NOX inhibitor researchers are currently studying for PBC. Early results of clinical trials have found that this medication may have antifibrotic effects and may improve fatigue (extreme tiredness).

Non-Bile Acid Farnesoid X-Receptor Agonists

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 acid and 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 Inhibitors

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, ursodeoxycholic acid, isn’t very effective at controlling itching for most people.

A small 2023 clinical trial showed that the IBAT inhibitor linerixibat significantly improved itching in people taking this medication for 12 weeks. A larger clinical trial for this medication is currently ongoing.

Changes in PBC Treatment Goals

New treatments for PBC have made it possible for health care providers to push for more aggressive treatment goals, which may help improve PBC outcomes.

Normalization of Liver Enzymes

Due to the slow disease progression of PBC, health care providers look at levels of substances like ALP and bilirubin to see how well a treatment is working. Researchers and health care providers use these levels to predict whether a person might need treatments like a liver transplant, for example. In clinical trials, ALP levels less than 1.67 times the upper limit of normal (ULN) levels and bilirubin levels at or below ULN levels are commonly used to help predict PBC outcomes.

New medications, such as PPAR agonists, may increase the chance of reaching normal levels of ALP and bilirubin. This may lead to more aggressive treatment goals for people with PBC.

Improving Symptoms

An article in the journal Digestive Diseases and Sciences found that up 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, such as obeticholic acid, can actually worsen PBC symptoms, including itching.

With the approval of newer effective PBC treatments, such as IBAT inhibitors, health care 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.

Joining a Clinical Trial

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 health care provider to see if you qualify for any in your area.

Find Your Team

On myPBCteam, the social network for people with primary biliary cholangitis and their loved ones, more than 1,600 members come together to ask questions, give advice, and share their tips with others who understand life with primary biliary cholangitis.

What PBC research are you interested in learning more about? Have you taken the newly approved PPAR agonists elafibranor or seladelpar? Share your experiences in the comments below, or start a conversation by posting on your Activities page.