The one I always mix up with PSC.
Primary Biliary Cirrhosis (PBC)
Definition: liver disease where interlobular bile ducts are damaged by chronic autoimmune granulomatous inflammation causing cholestasis which may lead to fibrosis, cirrhosis and portal hypertension.
Aetiology/ risk factors:
-autoimmune aetiology likely
-unknown environmental triggers + genetic predisposition (e.g. IL12A locus) leading to loss of immune tolerance to self-mitochondrial proteins. Antimitochondrial antibodies (AMA) are the hallmark of PBC = autoimmune response directed against bile duct epithelial cells.
-positive family history (seen in 1-6%)
-other autoimmune diseases e.g. Sjogren’s syndrome
-use of nail polish/ hair dye (weird…)
Epidemiology: prevalence is approx. ≤ 4/100,000
About 9x more common in females
Typical age at presentation is about 50 years
May present with:
-RUQ abdominal discomfort (rarely)
Which may be followed, years later, by
and other features of liver decompensation e.g. ascites, variceal bleeds
–Associated conditions e.g. Sjogren’s syndrome– dry eyes and dry mouth
-may show no signs early on
-scratch marks (from itching)
-xanthomata- deposition of yellowish cholesterol-rich material that can appear anywhere in the body (secondary to hypercholesteraemia)
-xanthelasma- xanthomata around the eyes
-Signs of complications e.g. liver cirrhosis- spider naevi, palmar erythema, ascites, clubbing
Palmar erythema (red hands)
LFTs- ↑Alkaline phosphatase, ↑GGT, mild ↑transaminases. Later stages- ↑Bilirubin & ↓albumin, ↑prothrombin time
Serology- increased immunoglobulins, especially ↑IgM
AMA +ve (anti-mitochondrial antibody)- 98% are AMA M2 subtype +ve
Other autoantibodies may occur in low titres
TSH (associated autoimmune thyroid disease) & Cholesterol are elevated or normal (hence the fatty xanthomata, the liver and bile are important in cholesterol metabolism)
Ca, Phosphate, 25-hydroxyvitamin D
Ultrasound- excludes extrahepatic cholestasis and obstruction (e.g. by gallstones or strictures)
Liver biopsy- not usually needed (unless drug-induced cholestasis or hepatic sarcoidosis need excluding)
Shows granulomas around intrapehatic bile ducts +/- cirrhosis (fibrosis and regenerating nodules of hepatocytes), and destruction of the intrahepatic bile ducts.
A granuloma is a focal collection of inflammatory cells at sites of tissue infection and includes activated macrophages (epithelioid cells), Langhans’ giant cells, and lymphocytes.
-No curative treatment with management focusing on symptom control
–COLESTYRAMINE (4-8g/24h PO) for pruritus. (Naltrexone and rifampicin may also help).
–Osteoporosis prevention/treatment e.g. Calcium and Vitamin D supplementation, bisphosphonates, exercise programme, periodic DXA scans.
-Fat soluble vitamin prophylaxis: vitamin A, D and K
-Consider high dose URSODEOXYCHOLIC ACID. If baseline bilirubin >24μmol/L, it may improve survival and delay transplant. (= hydrophilic bile acid which may decrease the toxicity or improve elimination of retained bile acids.)
-Regular monitoring of LFTs, ultrasound and AFP (increase risk of hepatocellular carcinoma)
⇒Liver transplant is the mainstay for end-stage disease or intractable pruritus.
-liver cirrhosis and associated complications:
-hepatocellular carcinoma- so check AFP tumour marker twice yearly
-hyperlipidaemia (due to cholestasis)
-malabsorption of fat-soluble vitamins (K, A, D, E) due to cholestasis and decreased bilirubin in gut results in:
-osteomalacia (vitamin D deficiency)
-coagulopathy (vitamin K deficiency- required for production of factors 2, 7, 9, 10)
Prognosis: histological recurrence in the graft post-transplant is ∼17% after 5 years. Although graft failure can occur as a result of recurrence, it is rare and unpredictable.
Once jaundice develops, survival is less than 2 years without transplantation.