The most likely diagnosis is primary biliary cirrhosis (PBC). PBC is a chronic cholestatic liver disease of unknown cause. PBC mainly affects middle-aged women. Most patients are asymptomatic at presentation but develop symptoms of PBC within 10 years; symptoms include fatigue, dry eyes, dry mouth, and pruritus. Hyperlipidemia is common, but jaundice, cutaneous hyperpigmentation, hepatosplenomegaly, and xanthelasmas are rarely observed at diagnosis. PBC is diagnosed by serum alkaline phosphatase levels greater than 1.5 times the upper limit of normal and typically normal serum total bilirubin levels. Serum aspartate (AST) and alanine (ALT) aminotransferase levels are typically less than five times the upper limit of normal. Serum antimitochondrial antibody is present in 90% to 95% of patients. For patients with undetectable serum antimitochondrial antibody levels, a liver biopsy is required for diagnosis. Treatment with ursodiol slows disease progression and may prevent or delay advanced disease and the need for liver transplantation.

Autoimmune hepatitis is a chronic inflammatory liver disease that is usually seen in women. The disease presentation ranges from asymptomatic to acute liver failure. Autoimmune hepatitis typically causes a predominant elevation of the serum ALT level rather than the serum alkaline phosphatase level, as was seen in this patient.

Cholangiocarcinoma is classified by location as intrahepatic and hilar/extrahepatic. Intrahepatic cholangiocarcinoma is typically asymptomatic until the tumor is advanced, at which time right upper quadrant discomfort, weight loss, and fever may be the only symptoms. An elevated serum alkaline phosphatase level may be noted. Risk factors for cholangiocarcinoma are primary sclerosing cholangitis, biliary atresia, chronic infection with liver flukes, and biliary cysts. This patient has no risk factors for cholangiocarcinoma, and that diagnosis would not explain her positive antimitochondrial antibody test.

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disorder that affects the intra- and extrahepatic bile ducts. Approximately 70% to 80% of patients with PSC have inflammatory bowel disease, usually ulcerative colitis. Serum alkaline phosphatase values are 3 to 10 times the upper limit of normal, and serum ALT and AST levels are two to three times the upper limit of normal. Serum total bilirubin levels may be normal in 60% of patients. PSC is not the most likely diagnosis in this patient because she has a positive antimitochondrial antibody test and does not have ulcerative colitis.