Primary biliary cholangitis (previously cirrhosis) Flashcards
Define primary biliary cholangitis and its pathophysiology.
An auto-immune condition in which the immune system gradually destroys bile ducts which take bile from the liver to the gut.
The trapped bile then builds up in the liver, where it causes inflammation and damage to liver cells. This can eventually lead to cirrhosis of the liver.
Which autoantibodies are present in PBC?
anti-mitochondrial antibodies +ve in >95%
What is the epidemiology of primary biliary cholangitis?
Usually affects middle-aged women (9:1 gender ratio).
Explain the molecular cause of primary biliary cholangitis.
Antimitochondrial antibodies (IgM) - directed against disease specific nuclear antigens (ANA)
What is the aetiology of PBC?
Autoimmune but genetic and environmental factors have also been proposed.
E.g. environmental trigger like infection, chemicals or toxin causes bile duct epithelial injury.
What are the risk factors for primary biliary cholangitis?
- Female (9:1)
- Age 45-60years
- Personal/FH history of AI disease e.g.
- Sjogren’s syndrome (80%)
- scleroderma/systemic sclerosis
- rheumatoid disease
- thyroid
- Smoking
- UTI
What are the signs and symptoms of PBC?
- PRURITUS + FATIGUE
Other:
- Hepatomegaly
- Weight loss - due to malabsorption
- Xanthelasma - PBC alters cholesterol metabolism
- Autonomic dysfunction - postural dizziness/blackouts
- Rarely discomfort in the RUQ
- Symptoms of associated AI conditions e.g. Sjogren’s dry eyes and mouth
- Advanced disease → liver decompensation (e.g. jaundice, ascites, variceal haemorrhage)
How do you diagnose PBC?
Diagnosis with the following 3 features:
- LFTs -cholestatic picture: raised ALP and GGT. May have rising bilirubin and transaminases
- Autoantibodies - AMA or specific to PBC ANA
- Liver biopsy - classic bile duct lesions with portal inflammation and granuloma formation. This is increasingly NOT being performed as bloods are valuable.
Other:
Bloods:
- Clotting - PT prolonged
- AMA and IgM increased
- Cholesterol
- TFTs
- Other: plasma calcium, phosphate, 25-hydroxyvitamin D
Scans
- US -Exclude hepatobiliary obstruction (e.g. by gallstones or strictures)
- MRCP
- OGD
How do you manage primary biliary cirrhosis?
- UDCA - less symptoms and slows disease progression
- +/- Immunomodulatory therapy - prednisolone first then azathioprine or MMF
Treatment of symptoms/complications:
Anti-pruritic treatment -
- cholestyramine (binds bile acids in GI),
- rifampicin (upregulates liver enzymes that metabolise factors which cause pruritus),
- naltrexone (opioid receptor antagonist, given if pt doesn’t respond to rifampicin)
Other:
Metabolic bone disease - Ca and Vit D supplementation . Bisphosphonates (alendronate/risedronate) for osteoporosis, exercise programme, periodic DXA scans
Fat-soluble vit replacement - Vit D, Vit A. Vit E and K may be required too if liver failure is awaiting transplant.
Portal hypertension - beta-blockers and endoscopic banding of varices. Transjugular intrahepatic portosystemic shunt (TIPS) may be inserted but this increases risk of hepatic encephalopathy.
Liver transplantation - in end-stage disease if bili >100 (uses MELD score to predict survival)
What does the MELD score use?
MELD score uses serum bilirubin, creatinine, and INR to predict survival.
What is the prognosis of PBC?
Disease progression is variable
Poor prognosis if low albumin and high serum bilirubin
Median survival from time of diagnosis is 10 years and 5 year survival after transplant is >70%. But PBC an recur in the transplanted liver.
What is the MOA of UDCA?
Bile acid analogue which may reduce toxicity or improve elimination of retained bile acids.
What are the 3 Ms of PBC?
IgM
anti-Mitochondrial antibodies (M2 subtype)
Middle aged females
Apart from anti-M2, what other Abs may be found in PBC?
Smooth muscle abs in 30%
AMA M2 in 98%
What are the complications of PBC?
- Cirrhosis -→ portal hypertension -→ varices and ascites
- Hypercholesterolaemia
- Osteomalacia/osteoporosis
- HCC (x20) - HCC is hepatoma
