Primary biliary cholangitis (PBC) was previously referred to as primary biliary cirrhosis. It is a disease that affects the small bile ducts that are located within the liver (intrahepatic bile ducts/Canals of Hering).
Pathophysiology
The aetiology of the disease is not fully understood as of yet. However, it is believed to be an autoimmune disease as there is presence of autoantibodies in almost all PBC patients. The most common autoantibody is anti-mitochondrial antibodies.
There is also a high incidence (within the individual or family members) of other autoimmune disease such as Sjögren’s syndrome (seen in almost 80% of patients), rheumatoid arthritis, systemic sclerosis, coeliac disease and scleroderma.
It causes progressive ductal damage and eventually loss of the bile ducts and eventually loss of the bile ducts which obstructs bile flow → cholestasis. Bile itself is damaging to to the liver and causes further bile duct loss (self-sustaining damage). This damage can then lead to fibrosis of the liver and ultimately cirrhosis.
Bile is made up of bile salts, phospholipids, conjugated bilirubin, cholesterol, bile pigments (which are products of Hb metabolism).
The function of bile is to aid absorption of insoluble fats through emulsification.
Bile is made in the liver, and stored in our gallbladder. The gallbladder is located between the right & quadrate lobes of the liver. It connects via the cystic duct to the common bile duct [CBD] (which is also joined by the common hepatic duct). The CBD then joins the pancreatic duct of the pancreas to form the Hepatopancreatic ampulla of Vater.
Cholecystokinin (CCK) is released from the duodenum when digesting food. It’s function is to cause the gallbladder to contract for the release of bile.
Obstruction to this bile flow causes back up of bile into the bloodstream.
⚠️ Risk factors
- Female gender - affects women at 9:1 ratio. This does often lead to male cases being missed as a result.
- Middle age - 45-60 years is the peak incidence.
- Autoimmune diseases or family history of autoimmune diseases
😷 Presentation
It may be asymptomatic early on in the disease process.
- ⭐️ Fatigue - often the first symptom.
- ⭐️ Itching - due to bile salt deposition in the skin. A classic presentation is itching in a middle-aged woman.
- ⭐️ Hypercholestrolaemia - due to cholesterol components of bile in the bloodstream.
- Xanthomata and xanthelasmata (xanthomas of the eyelids)
- Abdominal pain and GI disturbances
- Osteoporosis
- Pale stool and dark urine
- Hyperpigmentation (melasma) over pressure points (knuckles, elbows, knees).
- Dry eyes and dry mouth - associated Sjogren’s features.
- Cholestatic jaundice - absent in most patients and is the most common reason for missing diagnosis as we tend to believe that jaundice is common (however, for exam purposes it may be useful to associate jaundice of course)
Other features in advanced disease especially can be features seen in liver fibrosis and cirrhosis and ultimately liver failure such as hepatosplenomegaly ascites, portal hypertension, cirrhosis.
- Anti-Mitochondrial antibodies (M2 subtype)
- Middle aged females
- IgM
🔍 Investigations
- LFTs
- ALP - is most commonly the first enzyme to be raised with obstructive liver diseases.
- GGT - will also be elevated with cholestasis.
- Anti-mitochondrial antibodies - specifically the M2 subtype. It is highly specific (98%). It can be done with immunofluorescence or ELISA.
- Anti-nuclear antibodies - present in approximately 35% of patients.
- IgM - raised.
This is needed to rule-out extrahepatic causes of biliary obstruction before making a diagnosis of PBC. This can be done with:
- Abdominal (RUQ) ultrasound
- MRCP (magnetic resonance cholangiopancreatography)
🧰 Management
- 🥇 Ursodeoxycholic acid - first-line treatment. It is a bile-acid analogue. It functions to facilitate bile flow through the liver. It helps reduce intestinal absorption of cholesterol. It helps slow disease progression and improves symptoms.
- Colestyramine - for pruritus. It binds to bile acids to prevent its absorption in the gut.
- If there is a significant inflammatory/autoimmune component to the disease, we can use a steroid immunomodulator to reduce this. Prednisolone is our main option for this.
🏆 Liver transplantation is the only option.
🚨 Complications
- Advanced liver disease and all the associated complications that it comes with.
- Osteoporosis
- Non-Hodgkin’s lymphoma