With diseases of unknown cause, such as primary biliary cirrhosis, therapy is necessarily empirical and symptomatic and rarely highly effective. So it is with primary biliary cirrhosis. The list of treatments that have been tried in randomized controlled trials is long and includes penicillamine, azathioprine, colchicine, chlorambucil, cyclosporine, corticosteroids, and ursodeoxycholic acid (ursodiol). Only ursodiol has consistently shown modest benefit in several trials, at relatively large doses (13-15 mg/kg/day). Laboratory test results related to cholestasis show improvement (alkaline phosphatase, bilirubin, cholesterol, gamma glutamyl transpeptidase). At 4 years of treatment, there was a fairly definite survival benefit (31% reduction in deaths) when results of 3 large randomized trials including 553 patients were pooled and analyzed. Presumed modes of action are choleretic, immunomodulatory, cytoprotective and antioxidant effects.

The definitive treatment is liver transplantation. A severity index developed at the Mayo Clinic provides a reasonable estimate of short-term survival. It uses relatively simple clinical and laboratory variables and aids greatly in timing the need for transplantation. One year survival after transplant averages 90%. A problem is the advanced age of many patients when they become ill enough to warrant transplantation. One potential yardstick is to consider those suitable for transplant who, absent their liver disease, have a predictable survival of ten years.

Preventive treatment for patients with primary biliary cirrhosis when bilirubin starts to rise is directed against fat-soluble vitamin deficiencies by supplying water-soluble preparations of vitamins A, D, E and K, and against bony demineralization by providing calcium supplements, dermal estrogen and alendronate.

Symptomatic treatment for pruritus is often a challenge. The mainstay is cholestyramine, administered in conjunction with meals so as to time the arrival of the medication in the duodenum at the moment of bile release from the gallbladder. Other medications may be chelated by cholestyramine if taken together with it. If cholestryramine treatment fails to alleviate pruritus then one can resort to rifampin, phenobarbital, ultraviolet light exposure, naloxone infusion or repeated plasmapheresis. None of these are invariably effective. Artificial tears are useful for patients with the sicca syndrome.

Hypercholesterolemia, common in PBC, need not be treated since there does not appear to be an increase in vascular disease in these patients. Ascites is managed in the usual manner for chronic liver disease. For variceal hemorrhage TIPS is useful as a bridge to transplantation, being certain that the stent does not protrude too far into the main portal vein where it may interfere with the vascular anastomosis.