Primary Biliary Cirrhosis

Primary Biliary Cirrhosis pbc2007.pdf

Primary biliary cirrhosis (PBC),

a chronic progressive cholestatic liver disease,
an autoimmune disease characterized by inflammation and necrosis of intrahepatic bile ducts and subsequent liver failure.
It affects primarily middle-aged women, and is associated with other autoimmune disorders (for example, Sjögren's syndrome, arthritis, thyroiditis).

Diagnosis:

serum alkaline phosphatase is disproportionately elevated compared with the aminotransferases,
positive for antimitochondrial antibody, which is present in 95% of affected patients.
The diagnosis is confirmed and staged by percutaneous liver biopsy. ERCP is rarely used except in the patient who is negative for antimitochondrial antibody.

Approximately 30% of newly diagnosed patients are asymptomatic, but most develop symptoms within 2 to 4 years. Early symptoms are fatigue and pruritus, whereas jaundice, steatorrhea, osteoporosis, and xanthomata develop later. Muscle wasting and bleeding from portal hypertension are end-stage manifestations and indications for referral for liver transplantation. The most troublesome symptom, itching, usually responds to cholestyramine, 4 g three times daily, initially. Cholestyramine appears to bind the itch-promoting substance in the intestine and to lead to its excretion in feces, a process that presumably decreases its concentration in bodily fluids. Rifampin relieves itching in some patients, but often elevates the serum bilirubin. UVB light, methyltestosterone, opioid antagonists such as naloxone, and plasmapheresis have been successful in refractory pruritus. Blood levels of fat-soluble vitamins should be checked, particularly in jaundiced patients, and supplemented orally if low.

Treatment:
There is no proven, generally accepted treatment for the underlying disorder. No medical treatment has been shown to alter the natural history of PBC.

Ursodiol (ursodeoxycholic acid), 13 to 16 mg/kg daily, improves most liver function tests and may lessen itching.
Colchicine, 0.6 mg twice daily, also improves liver function tests but to a lesser degree than ursodiol. Colchicine therapy did decrease mortality due to liver failure in one study.
Methotrexate, 15 mg per week orally, improved symptoms, liver function tests, and histologic findings in an open-label trial but caused interstitial pneumonitis in 10% of patients. It should be used only in controlled trials.
Liver transplant