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

• Other serious coexistent conditions such as pre-existing advanced malignancy or severe cardiopulmonary disease which would be expected to limit life 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
• Hypertension and left ventricular hypertrophy documented on ECG in the last 2 years
• Recent (< 6 months) history of myocardial infarction or unstable angina
• history of psychosis
• Receiving cyclosporine, warfarin, tricyclic agents, carbamazepine, phenobarbital, rifampin, ketoconazole or itraconazole in the last 3 months