Did you receive a different liver diagnosis before learning you had primary biliary cholangitis (PBC)? You’re not alone. Many liver diseases share symptoms that can blur the lines, making it tough for health care providers to nail down the right diagnosis immediately. This guessing game can be frustrating, but it’s a necessary step to finally uncover the true cause and get the right treatment that will make a difference.

Primary biliary cholangitis — previously known as primary biliary cirrhosis — is a chronic autoimmune disease that slowly destroys the bile ducts in the liver. Over time, this damage leads to liver inflammation, fibrosis (scarring), and eventually cirrhosis (permanent liver scarring) if left untreated.

Getting a correct diagnosis for PBC can be tricky. PBC shares symptoms with other liver and autoimmune diseases, which can lead to confusion when it’s time for your doctor to make a diagnosis. Here, we’ll look at how PBC is usually diagnosed, why it’s sometimes confused with other conditions, and how doctors can tell the difference between PBC and similar diseases.

The Autoimmune Nature of PBC and How It Affects the Liver

PBC is an autoimmune disease, which means the body’s immune system mistakenly attacks healthy cells — in this case, the small bile ducts in the liver. These ducts help move bile, a fluid that aids digestion, out of the liver and into the intestines. When there’s damage to the bile ducts, bile builds up in the liver. Over time, this buildup can lead to inflammation and scarring.

As the liver tries to repair itself, scar tissue forms. This scarring makes it harder for the liver to function properly. If left untreated, this process can lead to cirrhosis — a severe stage of liver damage where normal liver function is seriously impaired. Cirrhosis can cause complications like liver failure, which may require a liver transplant.

Symptoms of PBC May Develop Slowly

Because PBC symptoms often develop slowly, many people don’t notice any signs until their liver has already been damaged. The most common symptoms include:

• Fatigue (feeling very tired)
• Itchy skin
• Dry eyes and mouth
• Jaundice (yellowing of the skin and eyes)

PBC Can Cause Other Health Issues

Because PBC affects how bile is processed, it can also lead to other problems. These can include:

• Difficulty digesting fats
• Vitamin deficiencies (especially vitamins A, D, E, and K)
• High cholesterol levels
• Osteoporosis (bone loss)

These issues highlight the importance of early diagnosis and treatment to slow down liver damage and manage symptoms.

How Is PBC Diagnosed?

Doctors may use a combination of blood tests, imaging, and sometimes a liver biopsy (tissue sample) to diagnose PBC. However, the key diagnostic tool for PBC is a blood test looking for antimitochondrial antibodies (AMAs). AMAs are found in about 95 percent of people with PBC, which makes this test one of the most reliable ways to detect the disease.

Sometimes, imaging tests like ultrasound or magnetic resonance imaging (MRI) tests are done to check for liver or bile duct problems. If there’s still uncertainty, a liver biopsy may be needed. This test involves taking a small sample of liver tissue to look for signs of inflammation or scarring and destruction of small bile ducts within the liver.

Can PBC Be Misdiagnosed?

PBC can be misdiagnosed, especially in its early stages when symptoms are mild or hard to figure out. It’s a relatively rare condition — between 1 and 15 out of 100,000 people wordlwide are living with the disease. According to Mayo Clinic, PBC is most likely to be diagnosed in middle-aged women, but anyone can develop it.

Fatigue, itching, and dry eyes or mouth are common symptoms in several other conditions, so it’s easy for doctors to think and check for other diseases. Misdiagnosis of PBC often occurs when people don’t have obvious signs of liver disease or when blood test results are unclear.

Conditions That Can Be Mistaken for PBC

Some diseases share symptoms with PBC and can lead to confusion when diagnosing them. These other conditions include:

• Primary sclerosing cholangitis (PSC)
• Autoimmune hepatitis (AIH)
• Biliary obstruction
• Drug-induced liver disease
• Sjögren’s syndrome
• Autoimmune thyroid disease

Primary Sclerosing Cholangitis

Like PBC, PSC also affects the bile ducts. However, PSC typically involves both the large and small bile ducts inside and outside the liver. The National Institute of Diabetes and Digestive and Kidney Diseases has found that PSC is also more common in males than in females and is often linked with inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis.

Symptoms such as fatigue and jaundice are similar in both diseases, but PSC has a different pattern on imaging tests. PSC also usually shows negative results for AMAs, which helps doctors distinguish between the two conditions.

Autoimmune Hepatitis

AIH is another autoimmune disease, but it mostly attacks the liver cells rather than the bile ducts. It shares symptoms like fatigue and jaundice with PBC, but AIH typically shows higher levels of different liver enzymes, such as alanine transaminase (ALT) and aspartate transaminase (AST).

AIH is diagnosed through blood tests that detect specific antibodies and may also require a liver biopsy. In some cases, people can have both PBC and AIH. This is known as overlap syndrome and can make diagnosis more complicated.

Common Errors in Diagnosis and Why They Happen

There are several reasons why PBC can be misdiagnosed or mistaken for other diseases. For one, the symptoms of PBC are similar to other diseases. Fatigue and itching, which are common in PBC, also occur in other liver conditions and autoimmune diseases, such as primary sclerosing cholangitis and autoimmune hepatitis.

Sometimes, people may have more than one liver condition at the same time, such as PBC and AIH. This can make diagnosis difficult, as both conditions cause similar symptoms.

Additionally, although AMA is found in most people with PBC, about 5 percent of those with the disease don’t have these antibodies. This can make the diagnosis unclear or increase the chances that you might be misdiagnosed with something else.

Differentiating PBC From Other Conditions

Getting the correct diagnosis of PBC involves careful testing and sometimes seeing a hepatologist (liver specialist) or a doctor who specializes in autoimmune diseases. The following strategies and tests can help confirm a diagnosis of PBC.

Liver Enzyme Levels

PBC usually leads to higher levels of alkaline phosphatase (ALP), a sign that the bile ducts may be damaged. Other liver diseases may cause increases in different liver enzymes, such as ALT and AST. These findings can help your doctor differentiate PBC from other conditions.

Antimitochondrial Antibodies

A positive AMA test result is a strong sign of PBC. If AMA is present and liver enzyme levels (especially ALP) are high, PBC is likely. This test is one of the most reliable ways to differentiate PBC from other liver diseases, such as PSC and AIH.

Liver Biopsy

If blood tests and imaging aren’t enough to confirm the diagnosis, a liver biopsy may be needed. In PBC, the biopsy can reveal bile duct damage, inflammation, and scarring. A biopsy can also rule out other liver diseases or identify overlap syndromes like PBC and AIH.

Consultation With a Specialist

Because PBC is rare, seeing a liver specialist or a gastroenterologist (specialist in diagnosing and treating problems with the digestive system) can help ensure an accurate diagnosis. Specialists are more familiar with PBC and other autoimmune liver diseases and are better equipped to order the right tests and interpret the results.

Early diagnosis and treatment are key to managing PBC and preventing serious liver damage. Don’t hesitate to reach out to your doctor or a liver specialist if you’re experiencing symptoms or want a second opinion on your diagnosis.

Talk With Others Who Understand

On myPBCteam, the social network for people with primary biliary cholangitis and their loved ones, more than 1,500 members come together to ask questions, give advice, and share their tips with others who understand life with primary biliary cholangitis.

Have you been misdiagnosed with another condition before receiving your proper diagnosis? What condition was your PBC mistaken for? Share your experiences in the comments below, or start a conversation by posting on your Activities page.