Modafinil in the Treatment of Fatigue in Patients With Primary Biliary Cirrhosis (PBC)

Inclusion Criteria: * Primary biliary cirrhosis will be defined as present when 2 of 3 of the following criteria are met: * Chronic cholestatic liver disease for greater than 6 months with alkaline phosphatase levels greater than 1.5 times the upper limit of normal prior to UDCA treatment. * Positive AMA titer greater or equal to 1:40 or AMA greater than 0.1U. Liver histology in the past with features consistent with or diagnostic of PBC. * A previous ultrasound, computed tomography (CT), or cholangiography of the biliary tree excludes biliary obstruction. * Verbal report of fatigue for greater than 6 months. Exclusion Criteria: * Patients with other serious coexistent conditions such as pre-existing advanced malignancy or severe cardiopulmonary disease which would be expected to limit their expectancy to less than three years. * Findings highly suggestive of liver disease of other etiology such as chronic alcoholic liver disease, chronic hepatitis B or C infection, hemochromatosis, Wilson's disease, 1-antitrypsin deficiency, non-alcoholic steatohepatitis or sclerosing cholangitis. * Treatment of underlying PBC has been modified in the preceding six months. * Anticipated need for transplantation in one year (Mayo survival model \<80% one-year survival without transplant) or MELD above 15. * Recurrent variceal bleeding, presence of diuretic-resistant ascites, or spontaneous encephalopathy. * Active drug or alcohol use. * History of drug and/or stimulant (e.g. methylphenidate, amphetamine, or cocaine) abuse. * Serum bilirubin \>4 mg/dl. * Serum creatinine over 1.4 mg/dl. * Pregnancy. * Breast-feeding. * Inability or unwillingness to practice contraceptive measures for the prevention of pregnancy if appropriate. * Other fatigue related diagnoses such as anemia, thyroid disease, renal failure, use of beta-blockers and untreated depression. * Known hypersensitivity to modafinil. * Uncontrolled hypertension. * Patients with hypertension and left ventricular hypertrophy documented on ECG in the last 2 years. * Recent (\<6 months) history of myocardial infarction or unstable angina. * Patients with history of psychosis. * Patients receiving cyclosporine, warfarin, tricyclic agents, carbamazepine, phenobarbital, rifampin, ketoconazole or itraconazole in the last 3 months.