Finding the Patient With Primary Biliary Cirrhosis

Rowen K. Zetterman, MD


February 27, 2015

In This Article

Treatment of PBC

Despite the presumption that PBC is an autoimmune disorder, immunosuppressive agents have not generally been efficacious as therapy. Because corticosteroids worsen bone disease in persons with PBC, extensive trials of steroids have not been undertaken, and azathioprine and methotrexate have not been shown to improve clinical disease. Budesonide, a synthetic corticosteroid with reduced systemic steroid side effects owing to first-pass metabolism by the liver, may have use in conjunction with UDCA in selected patients.[33]

UDCA is the approved therapy for PBC and appears to be especially effective in patients with early disease[34] when given at a dosage of 13-15 mg/kg/day. UDCA is currently the standard of care for patients with PBC. Men may respond less well to UDCA than women.

Although not a curative drug, patients receiving UDCA tend to have better health outcomes,[35] delayed progression of early disease,[36] an increase in life expectancy,[35] and an overall lower cost of care during the course of disease compared with patients receiving standard care.[35] In early disease, UCDA typically improves serum liver tests,[37] and a failure to improve alkaline phosphatase levels to less than twofold normal within 6 months of treatment is a poor prognostic sign and predicts treatment failure.[38]

Liver histology can improve during UDCA treatment. Delays in the development of esophageal varices[39] and the need for liver transplantation have been seen in UDCA trials. A 20% reduction in the numbers of patients presenting for transplantation between 1996 and 2006 was attributed to UDCA therapy.[40]

Controversy over the clinical effectiveness of UDCA in patients with PBC was prompted by two meta-analyses that raised questions about survival benefit.[41,42] The ideal patient for treatment with UDCA is a woman with early disease who has significant improvement in serum alkaline phosphatase levels during treatment. In these patients, UDCA therapy may improve survival to that of a similar age-matched cohort without PBC.[36]

Bezafibrate has been evaluated in 30 women with PBC[43]; therapy with this drug led to a reduction in serum levels of alkaline phosphatase, gamma-glutamyltransferase, alanine aminotransferase, cholesterol, and triglycerides and an improvement in clinical symptoms of itching. Even patients who experienced a return of pruritus when the drug was stopped had relief of itching when bezafibrate therapy was resumed.

Orthotopic liver transplantation remains an important treatment for patients with end-stage PBC. Indications for transplantation are the same as for patients with other end-stage liver diseases. Severe, unremitting pruritus and chronic fatigue have been used as indications for transplantation. Fatigue is a particularly difficult parameter to assess and should be viewed as an indication when other traditional complications, such as ascites or variceal hemorrhage, are present.

The 5-year survival of patients after liver transplantation for PBC is higher than 80%. Recurrent PBC can develop in the transplanted liver in 9%-35% of patients.[44] With recurrent disease, pruritus and jaundice are less than in pretransplant patients and liver tests may remain normal or minimally elevated, requiring the diagnosis to be established by histology.

Other complications of PBC include hypercholesterolemia, severe pruritus, and bone disease. It is not clear whether hypercholesterolemia needs to be treated, because an increased risk for atherosclerotic vascular disease has not been established.

Therapy for itching includes UCDA as an off-label, first-line treatment; the anion exchange resin cholestyramine, which is approved for treatment of itching; and such off-label drugs as rifampin and naltrexone.[45,46] Naltrexone is best avoided in patients with liver failure and advanced cirrhosis. Plasmapheresis, albumin dialysis, and ultraviolet phototherapy have also been tried as unapproved therapies for itching.[16,46]

Because of the increased prevalence of bone disease, especially in postmenopausal women with advanced hepatic fibrosis,[47] patients with PBC should be screened with dual-energy X-ray absorptiometry bone scans and treated with a program of exercise, calcium, and vitamin D replacement as needed. Bisphosphonate drug therapy can be used for patients with spine and hip T-scores less than 2.5.[48]


PBC is a chronic, progressive hepatic disease with biliary epithelial cell damage of interlobular bile ducts that can lead to cirrhosis with complications of portal hypertension. Patients often present with pruritus or fatigue, are AMA positive, and may respond to treatment with UDCA. Those without symptoms who have elevated alkaline phosphatase levels, especially women, or who have signs of cholestasis in the absence of likely causes should be evaluated for PBC.


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