At times, your primary biliary cholangitis (PBC) might feel like a runaway train. Previously known as primary biliary cirrhosis, PBC is a progressive liver disease that continues to worsen over time.

Doctors divide PBC into four stages based on severity of symptoms. Progression to a higher stage may be slowed with proper treatment.

In this article, we’ll discuss the four stages of PBC and their symptoms as the disease progresses. It’s important to reach out to your doctor if you think your PBC is reaching a new stage. The sooner you start treatment, the better chance you have of slowing disease progression.

Defining the Stages of Primary Biliary Cholangitis

PBC affects every person differently, but there are general characteristics and symptoms of each stage. Doctors and researchers use PBC stages to guide your treatment options and help you better understand your prognosis (outlook) with the disease.

Early-stage PBC might not cause any symptoms, so it can be difficult to tell what stage you have. The best way to determine your PBC stage is with a liver biopsy. During this procedure, your doctor will use a small needle to remove a piece of liver tissue. The sample is then sent to a lab, where a pathologist will examine it.

Pathologists specialize in histology, or the study of cells and tissues using a microscope. They define the four stages of PBC using histological findings, like inflammation and fibrosis (scar tissue buildup). Imaging studies such as ultrasound and CT and MRI scans also aid the diagnosis of PBC.

Keep reading to learn how PBC affects your liver as the disease progresses and what symptoms you may experience.

Stage 1 PBC

PBC is an autoimmune disease, meaning an overactive immune system attacks the body’s healthy tissues. People with PBC tend to have more immune cells in their liver. This creates inflammation that starts damaging the liver’s bile ducts. Your body uses the fluid bile to aid digestion. The small bile ducts in your liver carry bile into your small intestine and gallbladder.

In stage 1 PBC, these small bile ducts in your liver start becoming inflamed. This is known as portal inflammation. Your liver will still function as normal, and your blood work might not show any signs of liver damage. You also might not experience any symptoms because your bile ducts can still transport bile to your digestive system.

Around 95 percent of people with PBC make immune system proteins known as autoantibodies. These proteins mistakenly flag your body’s tissues for immune system destruction. Antimitochondrial antibodies (AMAs) are among the most common autoantibodies found in PBC. Some people with stage 1 disease may test positive for AMAs, which is measured with a simple blood test.

Your liver biopsy sample will show some inflammation with or without collections of immune cells. Known as granulomas or florid bile duct lesions, these collections are a sign your immune system is attacking your liver.

Stage 2 PBC

As PBC progresses to the second stage, inflammation begins spreading from the portal area to nearby tissues. This inflammation can damage and kill liver cells. Scar tissue also begins building up along the bile ducts. Your liver can still transport bile through the small ducts, so you likely won’t notice symptoms in PBC stage 2.

Your liver may not function as well as it used to at this point. If your doctor orders blood work to check your liver function, you may have abnormal results. Damaged bile ducts release the liver enzymes alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGTP) in your bloodstream. High ALP and GGTP levels can point to a PBC diagnosis. You may test positive for AMAs with stage 2 PBC before you begin experiencing symptoms.

Stage 3 PBC

Most people begin experiencing symptoms with stage 3 PBC. This is because the liver starts malfunctioning when more scar tissue builds up. Under a microscope, the pathologist will see fibrous tissue forming walls, or septae, in your liver. The walls block bile flow, causing it to back up in your liver — this is known as cholestasis.

The symptoms of stage 3 PBC are usually associated with cholestasis. You may experience pruritus (itchy skin) due to the buildup of bile acids (bile salts) in your bloodstream. These substances irritate your nerves and make you itch more than usual. Stage 3 PBC can also lead to fatigue — extreme tiredness that doesn’t improve with sleep or rest. (Fatigue sometimes occurs as the only symptom of stages 1 and 2.)

Liver function tests will show elevated liver enzymes, including alanine aminotransferase. Your doctor may also check your bilirubin level. Bilirubin is a byproduct made from the breakdown of red blood cells. A healthy liver normally filters and processes bilirubin in bile. However, high bilirubin levels tell your doctor that your liver can’t clear bile, and the fluid is leaking into your bloodstream. People with late-stage PBC may have elevated bilirubin levels.

Stage 4 PBC

The fourth stage of PBC is associated with cirrhosis — severe liver scarring. Your liver has fewer functional bile ducts and can’t efficiently transport bile to your digestive system. The bile backup in your liver can lead to other cholestasis symptoms, including jaundice and severe itching. People with jaundice have yellowing of their skin and eyes. It’s usually one of the first signs of liver damage.

Other PBC stage 4 symptoms are due to disease complications. For example, PBC can lead to portal hypertension, or high blood pressure in the liver’s large vein. Liver cirrhosis and portal hypertension may cause:

• Edema (swelling in feet and ankles)
• An enlarged spleen (an immune system organ) or liver
• Ascites (fluid buildup in the abdomen)
• Varices or swollen veins in the abdomen and esophagus (tube connecting the mouth and stomach)

Without enough bile, your digestive system will have a harder time breaking down and absorbing fats. This can lead to:

• Vitamin deficiencies in fat-soluble vitamins such as A, D, E, and K
• Osteoporosis (weak or brittle bones) due to low vitamin D levels
• Xanthomas (fatty lumps under the skin)
• High lipid (cholesterol) levels
• Weight loss
• Fat in stool

Managing Progression of Primary Biliary Cholangitis

As your PBC progresses, your doctor will likely change your care plan. You’ll need regular checkups to monitor for complications like osteoporosis and internal bleeding.

Unfortunately, there’s no cure or way to reverse PBC. Your liver can regenerate and grow new tissue, but PBC causes permanent damage. You’ll work closely with your doctor to find the best treatment plan to help slow disease progression and prevent the need for a liver transplant.

The U.S. Food and Drug Administration (FDA) has approved three PBC treatments. Ursodeoxycholic acid (UDCA) — also known as ursodiol (Actigall and Urso) — and obeticholic acid (Ocaliva) are bile acid medications. They help keep bile flowing from the liver into the digestive system to treat PBC and reduce the amount of bile salts in your body. These drugs are known to slow the progression of PBC but can’t reverse fibrosis.

Elafibranor (Iqirvo) is the third PBC treatment. It was approved by the FDA in June 2024. It works to address an underlying mechanism of PBC to block the production of bile acid. In clinical trials involving people with PBC, elafibranor was shown to reduce levels of ALP. Further research is needed to understand whether it affects disease progression.

Be sure to talk to your doctor if your PBC symptoms change over time. It may be a sign your disease is progressing. They can prescribe treatments to help relieve your symptoms, such as:

• Antihistamines to treat itchy skin
• Cholestyramine to bind bile salts in the intestines and reduce itching
• Vitamins and supplements to treat vitamin deficiencies
• Diuretics to treat fluid buildup from portal hypertension
• Immune-suppressive drugs such as prednisolone and azathioprine to curb inflammation

You can also ask your doctor for other tips to manage your PBC symptoms as your disease progresses.

Talk With Others Who Understand

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

Has your primary biliary cholangitis progressed since your diagnosis? How have you managed your disease over time? Share your experience in the comments below, or start a conversation by posting on your Activities page.