Primary biliary cirrhosis is a disease of unknown etiology, primarily of middle-aged women, characterized by slow progression of signs resulting ultimately in deep jaundice and death, usually from hepatic failure. The rate of progression varies in each individual case. Symptoms usually develop 2 to 4 years after diagnosis in asymptomatic patients, and the length of survival once patients become symptomatic is approximately 7 years. The disease is found in persons of all races. Women are afflicted 10 to 20 times more frequently than men, and familial clustering has been noted. Patients are usually diagnosed during the fifth or sixth decades of life, but patients as old as 80 and as young as 20 years old have been reported. Primary biliary cirrhosis does not occur in the pediatric population. The disease may be progressive and result as stated above, or patients may remain asymptomatic for prolonged periods. The chief pathologic feature is a nonsuppurative destructive cholangitis, characterized by the destruction of small intrahepatic bile ducts by a granulomatous reaction.

Characteristically, patients present with a predominant elevation of alkaline phosphatase of hepatic origin and associated abnormalities to include elevated IgM, positive antimitochondrial antibodies (AMA), hypercholesterolemia and mild hyperbilirubinemia. Elevation of the serum bilirubin is indicative of disease progression and is considered a poor prognostic sign. Antimitochondrial antibodies (AMA) are present in 95% of cases and are the most suggestive. Additionally, smooth muscle antibodies are found in one-third of patients. ANA may be found in as many as one-half of patients. Also, other abnormalities include thyroid antibodies, renal tubular antibodies and rheumatoid factor. Associated diseases include Sjogrens syndrome, scleroderma, rheumatoid arthritis, interstitial pneumonitis, RTA, thyroiditis, systemic lupus erythematosus, and CREST syndrome. Sjogrens syndrome is most often associated and presents with sicca syndrome.

A confirmatory liver biopsy is recommended for diagnosis and staging. There are four stages of the disease which include:

STAGE 1: A florid duct lesion which shows cellular damage and rupture with bile leakage of the small portal ductules. There is periportal lymphoid infiltration with CD4 and CD8 T cells along with monocytes, neutrophils and eosinophils. Granulomas are typical.

STAGE 2: Ductules undergo necrosis and proliferation.

STAGE 3: Septal fibrosis and bridging necrosis are present.

STAGE 4: This stage is characterized by cirrhosis.

Clinical findings include jaundice, hepatosplenomegaly and refractory pruritus most commonly but may also include palmar erythema, spider angiomata, hyperpigmentation, xanthomas, arcus senilis, clubbing of the digits and vitiligo. Complications include the development of portal hypertension with resultant pathologic fractures esophageal varices with upper GI bleeding, and ascites. Definitive diagnosis is best established by hepatic biopsy. The differential diagnosis consists of cholelithiasis or other mechanical obstructions of the common bile duct, primary sclerosing cholangitis, cholestatic sarcoidosis, hepatic malignancies, ampullary carcinoma, autoimmune cholangiopathy, and cholestatic drug reactions.

There are two therapeutic goals, symptomatic relief and possible curative therapy. Symptomatic relief of pruritus may be obtained by using high-dose cholestyramine (8 gm PO BID-QID), rifampin (10 mg/kg/day), doxepin (25 mg QHS and titrate upwards for effect), naloxone, or Ondasetron. One common complication of biliary obstruction is poor absorption of fat soluble vitamins A, D, and K; therefore, treatment should include oral or parenteral supplementation of these vitamins. Ursodiol at 12 to 15 mg/kg may be given in divided doses or as a single bedtime dose. Studies have shown ursodiol helps decrease the need for liver transplantation or death by 32%. Ursodiol is indicated for early disease only; this medication is contraindicated in patients with advanced disease. For advanced cases, orthotopic liver transplantation is the only curative treatment. The 1-year survival rate is 85 to 90%, and disease recurrence is low if appropriate immunosuppression is employed.