Preventive Therapy

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Because PBC is a progressive disease that often eventually results in the need for liver transplantation, it is particularly important that patients remain as healthy as possible to improve their long-term outcome. The major preventable complications of PBC include osteoporosis and variceal hemorrhage. However, it is important to counsel patients on other modifiable lifestyle choices as well. Particular attention should be paid to smoking and obesity because both have the potential to modify transplantation outcome.

Osteoporosis

It remains somewhat controversial whether osteoporosis is truly a complication of PBC. Although it is common among patients with PBC, this disease affects predominantly middle-aged women who are at risk for osteoporosis for other reasons. In any case, patients should be screened for osteopenia or osteoporosis using bone densitometry. All patients with PBC should take calcium and vitamin D, either as a supplement or as part of their regular diet. The bis-phosphonate etidronate has been shown to be safe in PBC, stabilizing bone loss in corticosteroid-treated patients. Caution should be used with these agents if patients have significant esophageal varices because of the risk of esophageal ulceration. Newer-generation bisphosphonates such as risedronate (Actonel) are likely safer, although no data specifically addressing this question are currently available. Other options include hormone replacement therapy, which has been shown not to worsen cholestasis in PBC but must be used with caution given the recent Women's Health Initiative trial, and calcitonin. UDCA therapy has not been shown to improve osteoporosis in PBC.

Esophageal Varices

Unlike with most forms of chronic liver disease, the presence of esophageal varices in PBC does not necessarily indicate the presence of cirrhosis. The granulomatous destruction of the bile ducts can also obliterate small portal vein branches, resulting in presinusoidal noncirrhotic portal hypertension, similar to that seen in hepatic sarcoidosis. As a consequence, patients with PBC may have significant portal hypertension even with fairly early, noncirrhotic-stage PBC; therefore, upper endoscopy to screen for varices should be performed at diagnosis. If present, varices should be managed with p-blockade and band ligation as appropriate. No validated interval for variceal screening has been identified. We have shown that it is very unlikely for patients to have varices with a platelet count of a 200,000/^L as a surrogate marker for hypersplenism secondary to portal hypertension. Consequently, endoscopy is performed every 1 to 2 years in those with platelets < 200,000/^L. Because variceal hemorrhage may not be a consequence of end-stage liver disease in PBC, a single bleed is generally not considered an indication for liver transplantation.

Hepatocellular Carcinoma

Although not preventable, hepatocellular carcinoma (HCC) is another important complication of PBC that requires mention. Although the prevalence of HCC in patients with PBC ranges widely in different studies, recent data suggest that the incidence of HCC among cirrhotic patients with PBC is similar to that found in patients with hepatitis C-induced cirrhosis. Consequently, as for patients with cirrhosis from chronic hepatitis C virus infection, patients with PBC should have screening sonograms once they have radiographic or histologic evidence of cirrhosis.

Hypercholesterolemia

One final point regarding preventive therapy is the issue of hypercholesterolemia. Increased total cholesterol is common in PBC and is believed to result from chronic cholestasis. This has naturally raised concerns about cardiovascular effects. A recent study confirmed earlier findings that there was no increased cardiac death among patients with PBC. In general, cholesterol levels will fall with cholestyramine therapy for pruritus and tend to come down as the disease progresses. If patients have other cardiac risk factors, there is no concern with using 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins), although they may not be necessary.

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