Primary biliary cholangitis (PBC) has typically been a disease with a poor prognosis rate. For years, many people diagnosed with it ultimately required a liver transplant, and even then, about 30% of patients saw the condition come back.
But over the last decade, three new drugs have arrived that have made life more manageable for people with PBC – and two were FDA-approved as recently as 2024.
"It's an exciting time for patients who live with PBC, since we now have a lot of treatment choices for them," says Meena Bansal, MD, chief of the Division of Liver Diseases at the Mount Sinai Icahn School of Medicine in New York City. "Thanks to new advances in screening and treatment, this is now a disease that never needs to come to end-stage liver disease and a liver transplant. We can potentially now stop it in its tracks."
Here's a look at some of the most promising advances.
New Revolutionary Treatments
For years, the first-line therapy for PBC has been a medication called ursodeoxycholic acid (Actigall, Urso). It helps to move bile through your liver, to improve liver function, and reduce liver scarring. But about 40% of patients don't respond to this treatment.
A second drug, obeticholic acid (Ocaliva), was approved in 2016 for patients with PBC who didn't respond well enough to ursodeoxycholic acid. It can be used alone, or with ursodeoxycholic acid. Its use is sometimes limited, because it can cause increased itching, notes Resham Ramkissoon, MD, a transplant hepatologist at University Hospitals Cleveland Medical Center. You also can't use it if you have advanced liver cirrhosis, because it can worsen your liver disease.
But in 2024, the FDA approved two new drugs to treat PBC:
Seladelpar (Livdelzi). Seladelpar helps to reduce bile buildup in your liver by turning on a special liver protein called peroxisome proliferator-activated receptor delta (PPAR-delta), says Ramkissoon. You take it as a pill once a day. A 2024 study published in The New England Journal of Medicine found that it significantly lowered alkaline phosphatase (ALP) levels, a common PBC marker. About 25% of the time, patients saw their ALP levels return to normal. It also reduced itching. It's considered safe to use in people who have cirrhosis, Ramkissoon says.
Elafibranor (Iqirvo). Like seladelpar, it helps your liver manage bile, by turning on two proteins: PPAR-alpha and PPAR-delta. Research shows that people who take this drug see big drops in their ALP levels. About 15% even reach normal levels. It's also taken once a day as a pill.
Both of these drugs can be used along with ursodeoxycholic acid, or alone in people who can't tolerate the two drugs together, says James Lee, MD, a gastroenterologist at Providence St. Joseph Hospital in Orange, California. While they aren't a cure for PBC, "they can help people live longer, and healthier, without need for a liver transplant," says Ramkissoon.
New Insights Into Diagnosis
Patients have traditionally been diagnosed with PBC if blood tests show high levels of the liver enzyme ALP, as well as anti-mitochondrial antibodies (AMA). But a small number – anywhere from 5% to 17% – of people with PBC are AMA negative. Traditionally, a liver biopsy has been required for these patients to prove that they definitively have the disease.
Fortunately, new tests are available that may mean you can skip the biopsy, says Lee. These check for the following two antibodies:
- Anti-sp100 antibody
- Anti-gp210 antibody
If you're positive, then you'll typically be diagnosed with PBC.
You also no longer need a liver biopsy to help guide staging of your PBC, says Bansal. A test called FibroScan, which got FDA approval in 2013, uses ultrasound to check your liver health and measure liver stiffness.
"We use it to see how much fibrosis, or liver scarring, you have," she explains. "We only rely on liver biopsies now in very rare scenarios, like we suspect that a patient may also have another liver condition, such as autoimmune hepatitis."
New Treatments on the Horizon
The following drugs are being studied to treat PBC:
Linerixibat. This drug is called an ileal bile acid transporter (IBAT) inhibitor. It works a little differently than other medications, because it affects the gut, not your liver. It blocks the IBAT protein, which helps your body reabsorb bile acid. As a result, you poop more bile acids out. The hope is it will be able to help reduce the itching that many people have with PBC.
Setanaxib. This is a type of drug called a NOX inhibitor. It blocks an enzyme called NADPH oxidase, which causes liver inflammation. Early-stage clinical trials have found that it lowers ALP levels and may even improve fatigue. It can cause mild side effects like a headache or upset stomach.
Tropifexor. This medication turns on your liver's FXR protein, which helps your liver make and move bile acids. It's thought the drug will help to prevent bile buildup, which can hurt your liver. It's been shown to improve a liver enzyme called gamma-glutamyl transferase (GGT), which suggests it may improve your liver function. But more studies are needed.
There are many clinical trials going on to test new treatments for PBC. You can ask your doctor about any near you. You can also search for clinical trials on the National Institute of Health website, here.
Takeaways
There are many new promising treatments and clinical trials for PBC. But it's also important to catch the disease early, before it progresses, stresses Bansal.
"PBC primarily affects women in their 50s," she says. "It's always a good idea to ask your primary care provider to check liver enzymes such as ALP once a year. If yours are elevated and you have other symptoms like itching, you can talk to your doctor about doing follow-up blood tests to check your AMA antibody levels."
