Primary biliary cholangitis/cirrhosis

Question 1

What is primary biliary cirrhosis?

Answer 1

An autoimmune disease where there is progressive lymphocyte-mediated destruction of intra-hepatic small bile ducts within the liver -> cholestasis -> cirrhosis.

Question 2

Describe the pathophysiology of primary biliary cirrhosis.

Answer 2

Autoimmune condition:
1.Serum antimitochondrial antibodies (AMA) cause chronic autoimmune granulomatous inflammation
2. Lymphocyte-mediated attack on the interlobular ducts
3. Destruction of the bile ducts
4. Causing cholestasis (obstruction of the outflow of bile)
5. May lead to fibrosis, cirrhosis and portal hypertension

• Likely that an environmental factor acts on genetically predisposed hosts
  to trigger disease

Question 3

Give 3 risk factors for primary biliary cirrhosis.

Answer 3

1. Positive family history
2. Frequent UTIs
3. Smoking
4. Past pregnancy
5. Other autoimmune disease
6. Use of nail polish/hair dye

Question 4

Describe 2 features of the epidemiology of primary biliary cirrhosis.

Answer 4

1. Females affected more than men.
2. Familial - 10 fold risk increase.
3. Typical age at presentation = 50 YO
4. Cause is unknown but its thought to be immunological and serum anti-mitochondrial antibodies (AMA) are found in almost all patients

Question 5

Give 5 symptoms of primary biliary cirrhosis.

Answer 5

1. Pruritus - Itching (the earliest symptom)
2. Lethargy and Fatigue.
3. Jaundice.
4. GI disturbance (pale stools) + abdominal pain - RUQ pain
5. Hypercholesterolaemia - Xanthoma and pigmented xanthelasma on eyelids
6. Signs of cirrhosis and failure (e.g. ascites, hepatosplenomegaly, spider naevi)

Question 6

Why is xanthoma and pigmented xanthelasma part of the clinical presentation for PBC?

Answer 6

1. Bile acids, bilirubin and cholesterol are usually excreted through the bile ducts into the intestines.
2. When there is obstruction to the outflow of these chemicals, they build up in the blood as they are not being excreted.
3. Raised cholesterol causes cholesterol deposits in the skin called xanthelasma (xanthomas are larger nodular deposits in the skin or tendons) and blood vessels, causing increased risk of cardiovascular disease.

Question 7

Why is pruritus (itching) part of the clinical presentation for PBC?

Answer 7

1. Bile acids, bilirubin and cholesterol are usually excreted through the bile ducts into the intestines.
2. When there is obstruction to the outflow of these chemicals, they build up in the blood as they are not being excreted.
3. Bile acids cause itching.

Question 8

Why is jaundice part of the clinical presentation for PBC?

Answer 8

1. Bile acids, bilirubin and cholesterol are usually excreted through the bile ducts into the intestines.
2. When there is obstruction to the outflow of these chemicals, they build up in the blood as they are not being excreted.
3. Bilirubin causes jaundice.

Question 9

Why is GI disturbance and pale stools part of the clinical presentation for PBC?

Answer 9

1. Bile acids are normally responsible for helping the gut digest fats.
2. Having a lack bile acids in the stool cause gastrointestinal disturbance, malabsorption of fats and greasy stools.
3. Bilirubin normally causes the dark colour of stools, so a lack of bilirubin can cause pale stools.

Question 10

Name the 3 investigations to do for PBC.

Answer 10

1. Bloods
2. Ultrasound
3. Liver biopsy

Question 11

Describe the blood test results for PBC diagnosis.

Answer 11

Bloods

1. LFTs:
   * Raised alkaline phosphatase (ALP) = unique to PBC = 1st liver enzyme to be raised
   * Raised GGT and bilirubin = raised later in disease
2. Autoantibodies:
   * Anti-mitochondrial antibodies (AMAs) - present in 95%, M2 antibody is
   98% specific = specific to PBC
   * Anti-nuclear antibodies - present in about 35% of patients
3. Others:
   * Raised serum cholesterol
   * Raised serum IgM
   * Raised ESR

Question 12

What other investigation, apart from blood tests, might you perform in PBC, and why?

Answer 12

Ultrasound:
* Can show a diffuse alteration in liver architecture and excludes
extrahepatic cholestasis

Question 13

What investigation would you use to diagnose + stage PBC?

Answer 13

Liver biopsy - used in diagnosing + staging

Shows characteristic histological features:
* Portal tract infiltrate, mainly of lymphocytes and plasma cells
* Around 40% have granulomas
* Damage to and loss of small bile ducts and ductular proliferation
* Portal tract fibrosis and eventually cirrhosis is seen

Question 14

Differential diagnoses for PBC.

Answer 14

• Differential diagnosis:

1. Autoimmune cholangitis.
2. Extrahepatic biliary obstruction should be excluded by ultrasound.

Question 15

Give 3 complications of PBC and its symptoms as the diseases progresses.

Answer 15

Complications:

1. Cirrhosis
2. Osteoporosis
3. Malabsorption of fat-soluble vitamins (A,D,E,K) due to cholestasis
4. Decreased bilirubin in the gut lumen results in osteomalacia and
   coagulopathy

Question 16

Treatment for primary biliary cirrhosis.

Answer 16

1. Ursodeoxycholic acid
   - Improves liver enzymes (bilirubin and aminotransferase levels)
   - Reduces inflammation and portal pressure and therefore the rate of variceal development.
2. Supplementation of Vitamin A,D,E,K (fat-soluble vitamins)
   - For malabsorption
3. Bisphosphonates
   - For osteoporosis
4. For pruritus - Cholestyramine
   - Bile acid sequestrate that binds to bile acid to prevent absorption in gut and reduce pruritus
   - Unpalatable (not pleasant to taste)

• Naloxone and Naltrexone - opioid antagonists = shown to help pruritus
• Immunosuppressants e.g. steroids in some patients

Question 17

Give 3 diseases associated with primary biliary cirrhosis.

Answer 17

1. Thyroiditis.
2. RA.
3. Coeliac disease.
4. Lung disease.

(Other autoimmune diseases).