Primary Biliary Cholangitis (PBC)

What happens in PBC

Bile is made in the liver and drains through tiny ducts into larger ducts and the intestine, carrying waste and helping digest fats. In PBC, immune cells attack the small bile ducts. As ducts are lost, bile backs up (cholestasis) and damages liver cells. Over years, this can cause fibrosis and eventually cirrhosis and liver failure. Progression is usually slow and varies widely between people. The name changed from "primary biliary cirrhosis" because most people diagnosed today do not have cirrhosis.

Causes and risk factors

PBC is autoimmune. The exact trigger is unknown, but a combination of genetic susceptibility and environmental factors is thought to be involved. Risk factors include:

• Female sex
• Age 40 to 60
• Family history of PBC
• Smoking
• Other autoimmune conditions, particularly Sjögren's syndrome, autoimmune thyroid disease, scleroderma and celiac disease

Symptoms

Many people have no symptoms and are diagnosed after routine blood tests. When present:

• Fatigue: the most common symptom, sometimes severe
• Itching (pruritus): often worse at night, on the palms and soles, without a rash
• Dry eyes and dry mouth
• Discomfort in the upper right belly
• Darkened skin and small yellow fatty deposits (xanthelasma) around the eyes
• Later signs: jaundice, swelling of the belly and legs, easy bruising, and complications of cirrhosis

Related problems

• Bone thinning (osteoporosis): common, due to poor absorption of vitamin D and calcium
• High cholesterol: common, but in PBC it does not appear to raise heart disease risk as much as usual
• Fat-soluble vitamin deficiency (A, D, E, K) in advanced disease
• Thyroid disease

Diagnosis

PBC can be diagnosed when two of the following are present:

1. Raised alkaline phosphatase (a liver enzyme linked to bile ducts)
2. Anti-mitochondrial antibodies (AMA) in the blood, found in about 90 to 95 percent of people with PBC. Other PBC-specific antibodies (sp100, gp210) help in AMA-negative cases
3. Liver biopsy showing typical bile duct damage, which is now rarely needed

Other tests:

• Ultrasound to rule out blocked bile ducts and look for cirrhosis
• Liver stiffness scans (elastography) to assess scarring
• Bilirubin, albumin and platelet count to assess severity
• Bone density scan
• Tests to exclude other conditions, such as primary sclerosing cholangitis and autoimmune hepatitis

Treatment

First-line treatment

Ursodeoxycholic acid (ursodiol, UDCA) is a bile acid taken by mouth every day for life. It improves bile flow, lowers liver enzymes and slows progression. Most people respond well, especially when treatment starts early. Response is checked with blood tests after 6 to 12 months.

Second-line treatments

About a third of people do not respond fully to ursodiol. Additional options include newer medicines such as PPAR agonists (elafibranor and seladelpar), and fibrates in some cases. A hepatologist chooses based on response, symptoms and liver function.

Symptom management

• Itching: cholestyramine, rifampin, naltrexone or sertraline, under medical guidance. Newer treatments may help.
• Fatigue: check for other causes such as thyroid disease, anemia, depression and sleep problems. Regular activity can help.
• Dry eyes and mouth: artificial tears and saliva substitutes.
• Bone health: calcium, vitamin D, weight-bearing exercise, and osteoporosis medicines if needed.

Liver transplant

For people with end-stage liver disease or severe, uncontrollable symptoms, liver transplant is highly successful. PBC can recur after transplant but usually progresses slowly.

Outlook

With early diagnosis and good response to ursodiol, many people with PBC have a near-normal life expectancy. Outcomes are less favorable when diagnosis is late or response to treatment is poor. Regular monitoring, avoiding alcohol and smoking, and vaccinations against hepatitis A and B help protect the liver.

Frequently asked questions

What is primary biliary cholangitis?

Primary biliary cholangitis is a chronic autoimmune liver disease in which the immune system damages the small bile ducts in the liver. Bile builds up and harms the liver, which can lead to scarring and cirrhosis over many years. It mostly affects women in middle age.

What are the first symptoms of PBC?

Many people have no symptoms and are diagnosed from abnormal routine blood tests. When symptoms occur, the earliest are often fatigue and itching without a rash, especially at night. Dry eyes and mouth are also common. Jaundice tends to appear later.

How is PBC treated?

The first treatment is ursodiol, a bile acid taken daily for life, which slows the disease in most people. If the response is incomplete, second-line medicines can be added. Symptoms such as itching and bone thinning are treated separately. Liver transplant is an option for advanced disease.

What is the life expectancy with PBC?

People diagnosed early who respond well to ursodiol often have a near-normal life expectancy. Those diagnosed with advanced disease or who do not respond to treatment have a higher risk of cirrhosis and liver failure, though second-line medicines and transplant improve outcomes.