Connect with others who understand.

Sign up Log in
About myPBCteam
Powered By
See answer

Primary Biliary Cholangitis News: What’s the Latest Research?

Medically reviewed by Adelina Hung, M.D.
Posted on November 15, 2024

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.

References
  1. Primary Biliary Cholangitis — Mayo Clinic
  2. Current Landscape and Evolving Therapies for Primary Biliary Cholangitis — Cells
  3. Expression of E-Cadherin by CD8+ T Cells Promotes Their Invasion Into Biliary Epithelial Cells — Nature Communications
  4. New Research Into Autoimmune Liver Condition Suggests Unique Cell Movements May Be Driving Disease — University of Birmingham
  5. Genome-Wide Association Studies (GWAS) — National Human Genome Research Institute
  6. The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS Update — Genes
  7. Environmental Factors, Medical and Family History, and Comorbidities Associated With Primary Biliary Cholangitis in Japan: A Multicenter Case-Control Study — Journal of Gastroenterology
  8. Role of Autoantibodies in the Clinical Management of Primary Biliary Cholangitis — World Journal of Gastroenterology
  9. Autoantibody — National Cancer Institute
  10. Primary Biliary Cholangitis: 2018 Practice Guidance From the American Association for the Study of Liver Diseases — Hepatology
  11. Management of Primary Biliary Cholangitis: Current Treatment and Future Perspectives — Turkish Journal of Gastroenterology
  12. Primary Biliary Cholangitis — The Lancet
  13. Novel Drug Approvals for 2024 — U.S. Food and Drug Administration
  14. A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis — The New England Journal of Medicine
  15. Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis — The New England Journal of Medicine
  16. PPAR Agonists in PBC: Where Do We Go From Here? Or How To Choose Between the New and the Old — Clinics and Research in Hepatology and Gastroenterology
  17. Primary Biliary Cholangitis: Promising Emerging Innovative Therapies and Their Impact on GLOBE Scores — Hepatic Medicine: Evidence and Research
  18. Setanaxib, a First-in-Class Selective NADPH Oxidase 1/4 Inhibitor for Primary Biliary Cholangitis: A Randomized, Placebo-Controlled, Phase 2 Trial — Liver International
  19. Impact of Setanaxib on Quality of Life Outcomes in Primary Biliary Cholangitis in a Phase 2 Randomized Controlled Trial — Hepatology Communications
  20. Farnesoid X Receptor Agonist Tropifexor Attenuates Cholestasis in a Randomised Trial in Patients With Primary Biliary Cholangitis — JHEP Reports
  21. Farnesoid X Receptor (FXR): Structures and Ligands — Computational and Structural Biotechnology Journal
  22. Glimmer: A Randomized Phase 2b Dose-Ranging Trial of Linerixibat in Primary Biliary Cholangitis Patients With Pruritus — Clinical Gastroenterology and Hepatology
  23. Impact of Pruritus on Quality of Life and Current Treatment Patterns in Patients With Primary Biliary Cholangitis — Digestive Diseases and Sciences

A myPBCteam Member

Wish there was an option to print this article.

November 21
All updates must be accompanied by text or a picture.

We'd love to hear from you! Please share your name and email to post and read comments.

You'll also get the latest articles directly to your inbox.

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service.
Privacy Policy
All updates must be accompanied by text or a picture.

Subscribe now to ask your question, get answers, and stay up to date on the latest articles.

Get updates directly to your inbox.

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service.
Privacy Policy

Thank you for subscribing!

Become a member to get even more: