Primary Biliary Cholangitis: What to Do When Treatment Isn’t Working
Health ConditionsLiver Disease

Switching Medications: What to Do if Your Primary Biliary Cholangitis Treatment Isn’t Working

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Published on March 20, 2026
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S ince there’s no cure for primary biliary cholangitis (PBC), the main treatment goal is to slow disease progression and ease symptoms, such as itching. The good news is that, for most people, the first-line treatment is often effective, and many stay on it for life.

“Everyone with PBC will start treatment with ursodeoxycholic acid (UDCA), as it’s a very effective therapy for most people,” says Akshata Moghe, MD, a gastroenterologist and assistant professor of gastroenterology, hepatology, and nutrition at McGovern Medical School at the University of Texas Health Science Center in Houston.

Sometimes, though, UDCA isn’t enough to keep the disease from progressing. In that case, your doctor may recommend adding another medication to the treatment regimen or switching to a different therapy altogether.

3 Reasons to Switch Primary Biliary Cholangitis Medications

While most people with PBC benefit from taking UDCA, some may need a different treatment approach. Here are a few factors that may prompt a change in treatment.

1. Alkaline Phosphatase Levels Haven’t Improved After 1 Year

Your doctor will monitor your levels of alkaline phosphatase (ALP), a liver enzyme that is an indicator of bile duct damage. This can be done with routine blood tests to help determine how well UDCA is working. Ideally, ALP levels should drop to less than 1.5 to 2 times the upper limit of normal (a range based on individual factors, such as age and sex).

If ALP numbers remain too high after a year of treatment, it can be a sign that PBC is progressing, despite treatment with UDCA. In that case, “We need to add or switch therapies,” says Dr. Moghe.

1. Alkaline Phosphatase Levels Haven’t Improved After 1 Year

2. You’re Experiencing Side Effects From UDCA

“Side effects to UDCA are pretty rare,” says Moghe. In fact, only about three to five percent of people who take the medication have side effects. But some people report experiencing itching, persistent diarrhea, or other gastrointestinal symptoms that make it difficult to continue treatment.

If side effects interfere with your quality of life or ability to keep taking the medication, your doctor may recommend switching to a different treatment.

2. You’re Experiencing Side Effects From UDCA

3. You’re Showing Signs of Cirrhosis

In some cases, PBC can continue to progress, despite treatment, to liver fibrosis (scarring) or cirrhosis (an advanced, irreversible form of scarring that can eventually lead to liver failure).

Your doctor will monitor your liver health with imaging tests, such as an ultrasound or liver elastography, to check for fibrosis or developing cirrhosis, says Areej Mazhar, DO, a physician who specializes in gastroenterology and hepatology at CaroMont Health in Gastonia, North Carolina, and volunteer with the American Liver Foundation (ALF). Some medications aren’t safe to take if you have cirrhosis, she says, so your doctor will want to monitor your liver and recommend treatment adjustments as needed.

PBC “can definitely progress,” says Moghe, “and these people may then benefit from liver transplantation.” In these cases, evaluation at a transplant center may be the next step.

3. You’re Showing Signs of Cirrhosis

Assess Your Primary Biliary Cholangitis Treatment Plan

Answer these questions to help determine whether you should ask your doctor about making changes to the current PBC treatment plan.

Should You Switch Primary Biliary Cholangitis Medications?

Question 1/5

How long have you been taking the current treatment?

  • A. Under a year
  • B. At least a year

Treatment Options for Primary Biliary Cholangitis

If the medication you’re currently taking isn’t properly controlling PBC or you’re having unpleasant side effects, you may want to consider a different treatment.

4 Treatment Changes Your Doctor May Recommend

If UDCA is not effective for you, your doctor may:

  1. Add another PBC medication. “If there was a partial or no response to UDCA, we add a second treatment, such as a peroxisome proliferator-activated receptor (PPAR) agonist or fibrate,” says Moghe. Adding a therapy to the regimen may be enough to lower ALP levels and slow disease progression.
  2. Prescribe medication for itching. Doctors can prescribe medication to help ease the itch that often accompanies PBC.
  3. Switch you to a new medication. If you have intolerable side effects from UDCA, switching to a new treatment may be an option, says Moghe.
  4. Consider a liver transplant. If the disease progresses, despite treatments, you may be a candidate for a liver transplant, though this is rarer, says Moghe.

If you have PBC, you may take one medication or a combination of treatments to help slow disease progression, prevent complications, and ease symptoms. For some, liver transplant surgery may also be an option.

Ursodiol This drug is the first-line treatment for PBC, as it contains UDCA, a naturally occurring bile acid that helps shuttle bile out of the liver and into the small intestine. This helps improve liver health and reduce liver scarring but rarely helps with symptoms such as itching and fatigue. “Fatigue is the hardest symptom to treat, and it may not improve at all,” says Dr. Mazhar.

Elafibranor This medication is thought to target multiple receptors in the liver — namely, PPAR alpha and PPAR delta — to lower levels of inflammation and bile acids in the liver. It may also improve symptoms such as fatigue and itching.

Seladelpar This drug targets the PPAR-delta receptor in the liver to lower ALP levels. It can be used in combination with UDCA or prescribed on its own for people who can’t tolerate UDCA. It may also help relieve itching.

Fibrates These drugs act on the PPAR receptors to lower inflammation levels in the liver. They’re typically used off label for people who don’t respond well to UDCA.

Liver Transplant Surgery If medications can’t stop PBC from progressing to cirrhosis, you may be a candidate for a liver transplant (although most people with the condition won’t need one). A liver transplant replaces the damaged liver with a healthy liver from a donor. In up to about one-third of cases, PBC returns after the procedure.

Vitamin Supplements Because PBC can interfere with your body’s ability to absorb fat-soluble vitamins, your doctor may recommend taking vitamins A, D, E, and K. Vitamin D may also help shore up bone health — a good thing, as PBC has been linked to osteoporosis and osteopenia. Always talk to your doctor before taking any supplements.

How to Talk to Your Doctor About Changing Treatments for Primary Biliary Cholangitis

If ALP levels haven’t improved enough after about a year of taking UDCA, you and your doctor may consider other options. Here are a few things to bring up at your next appointment.

7 Things to Tell Your Doctor

  1. How you’re feeling from day to day
  2. Whether you’re experiencing fatigue or itching — and how severe it is
  3. If any new symptoms have appeared or symptoms have worsened
  4. Whether you have concerns about your liver health tests
  5. If you’ve missed any medication doses
  6. If you have any concerns about affording the medication
  7. Whether you’ve developed any new health conditions

4 Tips for Switching Primary Biliary Cholangitis Treatments Successfully

If UDCA hasn’t worked for you, there are ways to successfully transition to a new or altered medication regimen.

The Bottom Line About Switching Treatments

If UDCA alone hasn’t been enough to keep ALP levels low or symptoms at bay, there are other medications or therapies you may be able to add to the treatment regimen. Rarely, a liver transplant is needed. “Some people do fine all their life with medications and close monitoring,” says Moghe.

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Yuying Luo, MD

Medical Reviewer

Yuying Luo, MD, is an assistant professor of medicine at Mount Sinai West and Morningside in New York City. She aims to deliver evidence-based, patient-centered, and holistic care for her patients.

Her clinical and research focus includes patients with disorders of gut-brain interaction such as irritable bowel syndrome and functional dyspepsia; patients with lower gastrointestinal motility (constipation) disorders and defecatory and anorectal disorders (such as dyssynergic defecation); and women’s gastrointestinal health.

She graduated from Harvard with a bachelor's degree in molecular and cellular biology and received her MD from the NYU Grossman School of Medicine. She completed her residency in internal medicine at the Icahn School of Medicine at Mount Sinai, where she was also chief resident. She completed her gastroenterology fellowship at Mount Sinai Hospital and was also chief fellow.

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Maria Masters

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Maria Masters is a contributing editor and writer for Everyday Health and What to Expect, and she has held positions at Men's Health and Family Circle. Her work has appeared in Health, on Prevention.com, on MensJournal.com, and in HGTV Magazine, among numerous other print and digital publications.

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